Supplementary Online ContentCarl Regillo, Wills Eye Hospital IRB, Philadelphia, United States Carl...

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Supplementary Online Content

Holz FG, Sadda SR, Busbee B, et al; Chroma and Spectri Study Investigators. Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and Spectri phase 3 randomized clinical trials. JAMA Ophthalmol. Published online May 2, 2018. doi:10.1001/jamaophthalmol.2018.1544

eAppendix 1. Institutional Review Boards and Ethics Committees eAppendix 2. Methods eAppendix 3. Results eTable 1. Full Eligibility Criteria for Chroma and Spectri eTable 2. Complement Factor I (CFI)-Profile Biomarker Status Definition eTable 3. Power and Minimum Detectable Difference for the Primary End Point for Each of Chroma and Spectri eTable 4. Participant Demographics and Baseline Characteristics in Chroma eTable 5. Participant Demographics and Baseline Characteristics in Spectri eTable 6. Week 48 Outcomes in Chroma, Intent-to-Treat Population eTable 7. Week 48 Outcomes in Spectri, Intent-to-Treat Population eTable 8. Geographic Atrophy Area Change from Baseline to Week 48 by CFI-Profile Biomarker Status, for Chroma and Spectri, Pooled and Separate eTable 9. Best-Corrected Visual Acuity Change From Baseline at Week 48 eTable 10. Adverse Event Overview, Ocular and Non-Ocular, First 48 Weeks, Chroma and Spectri Pooled eTable 11. Ocular Adverse Events in the Study Eye Occurring in ≥1% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled eTable 12. Non-Ocular Adverse Events Occurring in ≥1% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled eTable 13. Serious Ocular Adverse Events in the Study Eye, First 48 Weeks, Chroma and Spectri Pooled eTable 14. Non-Ocular Serious Adverse Events (SAEs) by MedDRA System Organ Class and Non-Ocular SAEs Occurring in ≥0.5% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled eTable 15. Adverse Events Leading to Death During the First 48 Weeks, Chroma and Spectri Pooled eTable 16. Adverse Events Leading to Treatment Discontinuation, First 48 Weeks, Chroma and Spectri Pooled eTable 17. Ocular and Non-Ocular Adverse Events of Special Interest, First 48 Weeks, Chroma and Spectri Pooled eTable 18. Increased Intraocular Pressure in the Study Eye and Fellow Eye, First 48 Weeks, Chroma and Spectri Pooled eTable 19. Neovascular Age-Related Macular Degeneration in the Study and Fellow Eyes, First 48 Weeks, Chroma and Spectri Pooled eFigure 1. Adjusted Mean Geographic Atrophy Area Change From Baseline to Week 48 eFigure 2. Adjusted Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Chroma and Spectri Pooled eFigure 3. Adjusted Mean Change in GA Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Lampalizumab q4w Versus Sham eFigure 4. Adjusted Mean Change in GA Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Lampalizumab q6w Versus Sham eFigure 5. Mean Change in Best-Corrected Visual Acuity Over Time From Baseline to Week 48 eFigure 6. Mean (A) Pre-Dose and (B) Post-Dose Intraocular Pressure (IOP) in mm Hg Over Time in the Study Eye, First 48 Weeks, Chroma and Spectri Pooled

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eAppendix 1. Institutional Review Boards and Ethics Committees Institutional Review Boards and Ethics Committees for Chroma Study Sites Alan Cruess, Nova Scotia Health Authority Research Ethics Board, Halifax, Canada Alan Luckie, Bellberry Human Research Ethics Committee, Eastwood, Australia Alan Ruby, Quorum, Seattle, United States Alberto Zambrano, Comite de Etica en Investigacion Clinica (CEIC), Buenos Aires, Argentina Ali Tabassian, Quorum, Seattle, United States Allen Thach, Quorum, Seattle, United States András Seres, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Andre Witkin, Western International Review Board, Puyallup, United States Anita Agarwal, Vanderbilt University Institutional Review Board, Nashville, United States Attila Vajas, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Bahram Bodaghi, CPP Ile de France V, Paris, France Balazs Varsanyi, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Baljean Dhillon, NRES Committee North East - Newcastle & North Tyneside 1, Jarrow, United Kingdom Barbara Blodi, Western International Review Board, Puyallup, United States Blandina Lipkova, Ethics Committee of the Hospital Žilina, Žilina, Slovakia Bożena Romanowska-Dixon, Komisja Bioetyczna przy Okręgowej Izbie Lekarskiej w Gdańsku, Gdańsk, Poland Brad Baker, Quorum, Seattle, United States Brandon Busbee, Quorum, Seattle, United States Brian Berger, Quorum, Seattle, United States Carlos Zeolite, Comite de Etica en Investigacion Clinica (CEIC), Buenos Aires, Argentina Carmelina Gordon, Quorum, Seattle, United States Caroline Laugesen, De Videnskabsetiske Komiteer for Region Hovedstade, Hillerod, Denmark Carsten Framme, Ethik-Kommission der Medizinischen Hochschule Hannover, Hannover, Germany Catherine Francais, CPP Ile de France V, Paris, France Christopher Brand, NRES Committee North East - Newcastle & North Tyneside 1, Jarrow, United Kingdom Clement Chan, Quorum, Seattle, United States Daniel Pauleikhoff, Ethik-Kommision der Ärztekammer Westfalen-Lippe, Münster, Germany Dante Pieramici, Quorum, Seattle, United States Darma Ie, Quorum, Seattle, United States David Boyer, Quorum, Seattle, United States David Callanan, Quorum, Seattle, United States David Eichenbaum, Quorum, Seattle, United States David Lozano Rechy, Comite de Etica en Investigacion de Mexico Centre for Clinical Research SA de CV, Distrito Federal Mexico, Mexico David Maberley, UBC Clinical Research Ethics Board, Vancouver, Canada Dennis Marcus, Quorum, Seattle, United States Dilsher Dhoot, Quorum, Seattle, United States Dorota Raczyńska, Komisja Bioetyczna przy Okręgowej Izbie Lekarskiej w Gdańsku, Gdańsk, Poland Eric Souied, CPP Ile de France V, Paris, France Federico Furno Sola, Comite de Etica en Investigacion Clinica (CEIC), Buenos Aires, Argentina Federico Ricci, Ce Indip. Presso la fond. Ptv Policl. Tor Vergata, Roma, Italy Francesco Boscia, Comitato Di Bioetica Della ASL Di Sassari, Sassari, Italy Francesco Viola, Comitato Etico Milano Area B, Milano, Italy Frank Holz, Ethikkommission an der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn, Bonn, Germany G. Dijkman, METC AMC, Amsterdam, The Netherlands George Novalis, Quorum, Seattle, United States



Ghassan Ghorayeb, Chesapeake Research Review; IRB, Columbia, United States Glenn Stoller, Quorum, Seattle, United States Gregg Kokame, Quorum, Seattle, United States Gregory A. Fox, Quorum, Seattle, United States Guillermo Reategui, Comité de Bioética de la Clínica Anglo Americana, Lima, Peru Hedviga Mikova, Eticka komisia Nemonia Sveteho Michala, Bratislava, Slovakia H-Logan Brooks-Jr, Quorum, Seattle, United States Howard Fine, Quorum, Seattle, United States Ivan Suner, Quorum, Seattle, United States James Combs, Quorum, Seattle, United States Jared Nielsen, Quorum, Seattle, United States Javier Araiz, Comité Ético de Investigación Clínica de La Comunidad Autónoma del País Vasco (CEIC-E), Vitoria, Spain Javier Araiz, Comité Ético de Investigación Clínica, Barcelona, Spain Javier Montero, Comité Ético de Investigación Clínica, Barcelona, Spain Jeffrey Chang, Lahey Clinic IRB, Burlington, United States Jeffrey Heier, Quorum, Seattle, United States Jeffrey Moore, Quorum, Seattle, United States Jeffrey Zheutlin, Quorum, Seattle, United States Jennifer Arnold, Bellberry Human Research Ethics Committee, Eastwood, Australia Jordi Mones, Comité Ético de Investigación Clínica, Barcelona, Spain Jorge Fortun, Human Subjects Research Office (HSRO), Miami, United States Jorge Mataix, Comité Ético de Investigación Clínica, Barcelona, Spain Julie De Zaeytijd, UZ Gent, Commissie voor Medische Ethiek, Gent, Belgium Karl Olsen, Quorum, Seattle, United States Laura Sararols, Comité Ético de Investigación Clínica, Barcelona, Spain Laurent Lalonde, Quorum, Seattle, United States Lawrence Singerman, Quorum, Seattle, United States Lebriz Altay, Ethikkommission der Medizinischen Fakultät Universität zu Köln, Köln, Germany Luis Arias, CEIC Hospital de Bellvitge, Barcelona, Spain Luis Arias, Comité Ético de Investigación Clínica, Barcelona, Spain Manjot Gill, Northwestern University Office for the Protection of Research Subjects, Chicago, United States Marek Kacerík, Eticka Komisia pri FN Trencin, Trencin, Slovakia Maria Cristina Parravano, Comitato Etico Centrale Sezione IFO - Bietti Istituti Fisioterapici Ospitalieri, Roma, Italy Mark Gillies, Sydney Local Health District Ethics Review Committee (RPAH Zone), Newtown, Argentina Mark Michels, Quorum, Seattle, United States Matthew Wood, Quorum, Seattle, United States Michael Ober, Quorum, Seattle, United States Miguel Busquets, Quorum, Seattle, United States Nicolas Feltgen, Ethik-Kommission der Universität Göttingen, Göttingen, Germany Nicole Eter, Ethik-Kommision der Ärztekammer Westfalen-Lippe, Münster, Germany Nicole Schnelzer, Ethikkommission des AKH Linz, Linz, Austria Patricio Schlottmann, Comite de Etica en Investigacion Clinica (CEIC), Buenos Aires, Argentina Patrick Higgins, Quorum, Seattle, United States Paul Lee, Quorum, Seattle, United States Paul Mitchell, Bellberry Human Research Ethics Committee, Eastwood, Australia Paul Raskauskas, Quorum, Seattle, United States Peter Kertes, Sunnybrook Science Health Center, Toronto, Canada Philip Ferrone, Quorum, Seattle, United States Pravin Dugel, Quorum, Seattle, United States Rafael Ufret-Vincenty, University of Texas Southwestern, Dallas, United States



Raj Maturi, Quorum, Seattle, United States Rajiv Shah, Wake Forest University Eye Associates; Wake Forest University Health Sciences IRB Office, Winston-Salem, United States Ramin Tadayoni, CPP Ile de France V, Paris, France Randy Katz, Quorum, Seattle, United States Reinier Schlingemann, Academisch Medisch Centrum, Amsterdam, Netherlands Richard Feist, Western International Review Board, Puyallup, United States Ricky Isernhagen, Quorum, Seattle, United States Robert Bhisitkul, UCSF Committee on Human Research Office, San Francisco, United States Robert Hampton, Quorum, Seattle, United States Robert Johnson, Quorum, Seattle, United States Robert Kwun, Quorum, Seattle, United States Robert Stoltz, Quorum, Seattle, United States Robert Wirthlin, Quorum, Seattle, United States Robert Wong, Quorum, Seattle, United States Ronald Gentile, New York Eye & Ear Infirmary; Icahn School of Medicine at Mount Sinai, New York, United States Ryan Tarantola, Quorum, Seattle, United States Salomon Yves Cohen, CPP Ile de France V, Paris, France Salvatore Grisanti, EK Lübeck, Lübeck, Germany Sam Mansour, Quorum, Seattle, United States Sanford Chen, Quorum, Seattle, United States Seong Lee, Quorum, Seattle, United States Shelley Boyd, St Michael's Hospital, Toronto, Canada Slawomir Teper, Komisja Bioetyczna przy Okręgowej Izbie Lekarskiej w Gdańsku, Gdańsk, Poland Soraya Rofagha, Quorum, Seattle, United States Stephan Michels, Kantonale Ethikkommission Zürich (KEK), Zürich, Switzerland Steven Schwartz, UCLA Office of the Human Research Protection Program, Los Angeles, United States Stuart Burgess, Quorum, Seattle, United States Sumit Sharma, The Cleveland Clinic IRB, Cleveland, United States Sunil Gupta, Quorum, Seattle, United States Sunil Patel, Quorum, Seattle, United States Todd Schneiderman, Quorum, Seattle, United States Veeral Sheth, Quorum, Seattle, United States Victor Gonzalez, Quorum, Seattle, United States Virgilio Morales Canton, Comité de ëtica en Investigación de la Asociación para Evitar la Ceguera en México I.A.P.; CEI, Ciudad De Mexico, Mexico Vrinda Hershberger, Quorum, Seattle, United States Institutional Review Boards and Ethics Committees for Spectri Study Sites Alan Gordon, Quorum, Seattle, United States Alexander Eaton, Quorum, Seattle, United States Alfredo Garcia-Layana, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Allen Ho, Quorum, Seattle, United States Anders Kvanta, Regionala Etikprövningsnämnden i Stockholm Karolinska Institute, Stockholm, Sweden Andreea Gamulescu, Ethik-Kommission der Universität Regensburg, Regensburg, Germany Andrej Cernak, Etická komisia UN Bratislava, Bratislava, Slovakia Andrew Lotery, NRES Committee South Central–Berkshire, Bristol, United Kingdom Andrew Browning, NRES Committee South Central–Berkshire, Bristol, United Kingdom Andrew Antoszyk, Quorum, Seattle, United States Andrey Zolotarev, Samara State Medical University, Samara, Russian Federation



Angela Carneiro, CEIC - Comissão de Ética para Investigação Clínica, Lisboa, Portugal Anthony Kwan, Bellberry Human Research Ethics Committee, Eastwood, Australia Armin Wolf, Ethikkommission der Medizinischen Fakultät, Muenchen, Germany Arturo Alezzandrini, Comite de Etica en Investigacion Clinica (CEIC), Ciudad Autonoma de Buenos Aires, Argentina Balazs Varsanyi, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Bora Eldem, Hacettepe University Medical Faculty Clinical Research Ethics Committee, Ankara, Turkey Brian Connolly, Quorum, Seattle, United States Cameron Javid, Quorum, Seattle, United States Carl Regillo, Wills Eye Hospital IRB, Philadelphia, United States Carl Baker, Quorum, Seattle, United States Carel Hoyng, METC AMC, Amsterdam, The Netherlands Carlos Fernandez, CE para la Invest. Univ de San Martín de Porres, Lima, Peru Catherine Creuzot Garcher, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Charles C. Wykoff, Quorum, Seattle, United States Chiara Eandi, A.O. Città della salute e della scienza di Torino; Comitato Etico, Torino, Italy Chris P. Lohmann, Ethikkommission Technische Universität München, München, Germany Christina Flaxel, OHSU IRB, Portland, United States Christine R. Gonzales, Quorum, Seattle, United States Clare Bailey, NRES Committee South Central–Berkshire, Bristol, United Kingdom Daniel Miller, Quorum, Seattle, United States Dante Pieramici, Quorum, Seattle, United States David Sarraf, UCLA Office of the Human Research Protection Program, Los Angeles, United States David Eichenbaum, Quorum, Seattle, United States David Williams, Quorum, Seattle, United States David Saperstein, Quorum, Seattle, United States David M. Brown, Quorum, Seattle, United States Deeba Husain, Quorum, Seattle, United States Devinder Chauhan, Bellberry Human Research Ethics Committee, Eastwood, Australia Diana Do, University of Nebraska Medical Center IRB, Omaha, United States Eleonora Lad, Duke University Health System IRB, Durham, United States Elmira Abdulaeva, SAHI Republic Clinical Ophthalmological Hospital of Ministry of Health of Tatrstan Republic, Kazan, Russian Federation Eric Suan, Quorum, Seattle, United States Ewa Herba, Komisja Bioetyczna przy Bydgoskiej Izbie Lekarskiej, Bydgoszcz, Poland Faruque Ghanchi, NRES Committee South Central–Berkshire, Bristol, United Kingdom Francesco Bandello, Comitato Etico Irccs Ospedale San Raffaele, Milano, Italy Francisco Gomez Ulla, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Francisco Gomez Ulla, Comité Ético de Investigación Clínica de Galicia - Subdirección Xeral de Farmacia e Produtos Sanitar, Santiago de Compostela–A Coruña, Spain Francois Devin, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Fred Chen, Bellberry Human Research Ethics Committee, Eastwood, Australia Gary Abrams, Wayne State University Human Investigation Committee, Detroit, United States Gerd Auffarth, Ethikkommission der Medizinischen Fakultät Heidelberg, Heidelberg, Germany Gianni Virgili, Comitato Etico Area Vasta Centro, Firenze, Italy Giovanni Staurenghi, Comitato Etico Interaziendale Milano Area A, Milano, Italy Gursel Yilmaz, Hacettepe University Medical Faculty Clinical Research Ethics Committee, Ankara, Turkey Hansjurgen Agostini, Ethik-Kommission der Albert-Ludwigs-Universität, Freiburg, Germany Henry Ferreyra, UCSD Human Research Protections Program, La Jolla, United States H Logan Brooks Jr, Quorum, Seattle, United States Ian Pearce, NRES Committee South Central–Berkshire, Bristol, United Kingdom



Jagjit Gilhotra, Bellberry Human Research Ethics Committee, Eastwood, Australia Jakub Kaluzny, Komisja Bioetyczna przy Bydgoskiej Izbie Lekarskiej, Bydgoszcz, Poland Jale Mentes, Hacettepe University Medical Faculty Clinical Research Ethics Committee, Ankara, Turkey Janos Nemeth, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Jared Nielsen, Quorum, Seattle, United States Jean Francois Korobelnik, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Jerzy Nawrocki, Komisja Bioetyczna przy Bydgoskiej Izbie Lekarskiej, Bydgoszcz, Poland Joel Pearlman, Quorum, Seattle, United States Jonathan Williams, Quorum, Seattle, United States Jorge Calzada, Quorum, Seattle, United States Jose Manuel Ortiz, CEIC Complejo Hospitalario de Albacete, Albacete, Spain Jose Manuel Ortiz, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain William Bridges Jr, Quorum, Seattle, United States Juan Ramirez Estudillo, Comite de Etica en Investigacion de Mexico Centre for Clinical Research SA de CV, Distrito Federal, Mexico Julie Jacob, UZ Leuven Gasthuisberg, Commissie Medische Ethiek, Leuven, Belgium K. Bailey Freund, Quorum, Seattle, United States Katharina Bell, Ethik-Kommission der Landesärztekammer Rheinland-P, Mainz, Germany Katja Hatz, Ethikkommission Nordwest- und Zentralschweiz (EKNZ), Basel, Switzerland Larry Halperin, Quorum, Seattle, United States Lars-Olof Hattenbach, Ethik-Kommission der Landesärztekammer Rheinland-P, Mainz, Germany Laurent Kodjikian, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Laurence Postelmans, CHU Brugmann (Victor Horta), Comité d'Ethique, Bruxelles, Belgium Lawrence Morse, UC Davis IRB, Sacramento, United States Leonard Feiner, Quorum, Seattle, United States Lloyd Clark, Quorum, Seattle, United States Lucian Del Priore, MUSC Office of Research Integrity Institutional Review Board, Charleston, United States Mark Johnson, Quorum, Seattle, United States Mark Wieland, Quorum, Seattle, United States Marta Figueroa, CEIC Hospital Universitario La Princesa, Madrid, Spain Marta Figueroa, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Marta Misiuk-Hojło, Komisja Bioetyczna przy Bydgoskiej Izbie Lekarskiej, Bydgoszcz, Poland Massimo Nicolo, Comitato Etico Regione Liguria (Sezione 2), Genova, Italy Matthew Ohr, Western Institutional Review Board, Puyallup, United States Mauricio Martinez Cartier, Comite de Etica en Investigacion Clinica (CEIC), Ciudad Autonoma de Buenos Aires, Argentina Michael Larsen, De Videnskabsetiske Komiteer for Region Hovedstade Regionsgarden, Hillerod, Denmark Michael Williams, NRES Committee South Central–Berkshire, Bristol, United Kingdom Michel Weber, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Miguel Guzman, Comité Institucional de Etica en Investigación de la Asociación Benéfica Prisma, Lima, Peru Mimi Liu, Quorum, Seattle, United States Nancy Holekamp, Quorum, Seattle, United States Nauman Chaudhry, Quorum, Seattle, United States Nieraj Jain, Western Institutional Review Board, Puyallup, United States Nikolas London, Quorum, Seattle, United States Niro Narendran, NRES Committee South Central–Berkshire, Bristol, United Kingdom Nur Kir, Hacettepe University Medical Faculty Clinical Research Ethics Committee, Ankara, Turkey Paolo Lanzetta, Comitato Etico Regionale Unico CERU, Udine, Italy Paul Weishaar, Quorum, Seattle, United States Peter Campochiaro, Johns Hopkins Medicine Institutional Review Board, Baltimore, United States Peter Pavan, Quorum, Seattle, United States



Péter Vámosi, Medical Research Council, Ethics Committee for Clinical Pharmacology, Budapest, Hungary Philip Rosenfeld, University of Miami Miller School of Medicine; Human Subject Research Office, Miami, United States Prema Abraham, Quorum, Seattle, United States Quresh Mohamed, NRES Committee South Central–Berkshire, Bristol, United Kingdom Osman Saatci, Hacettepe University Medical Faculty Clinical Research Ethics Committee, Ankara, Turkey Rafael Navarro, Instituto de Microcirugia Ocular; CEIC, Barcelona, Spain Rafael Navarro, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Ramon Torres Imaz, CEIC Hospital Clinico San Carlos, Madrid, Spain Ramon Torres Imaz, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Raymond Sjaarda, Quorum, Seattle, United States Renata Garcia Franco, CEI Instituto Mexicano de Oftalmologia; Comite de Etica en Investigacion, Quereta, Mexico Richard Gale, NRES Committee South Central–Berkshire, Bristol, United Kingdom Richard Breazeale, Quorum, Seattle, United States Richard Dreyer, Quorum, Seattle, United States Robert Rosa, Scott and White Memorial Hospital, Temple, United States Robert C. Wang, Quorum, Seattle, United States Roberto Gallego-Pinazo, CEIC de Navarra; Departamento de Salud. Pabellón de Docencia., Pamplona, Spain Roberto Gallego-Pinazo, Comite Ético de Investigacion Clinica; Hospital Universitari I Politecnic LA FE, Valencia, Spain Robyn Guymer, Human Research and Ethics Committee Royal Victorian Eye and Ear Hospital, East Melbourne, Australia Rufino Silva, CEIC–Comissão de Ética para Investigação Clínica, Lisboa, Portugal Saddek Mohand Said, CPP Sud Ouest Et Outre Mer III, Bordeaux, France Sajjad Mahmood, NRES Committee South Central–Berkshire, Bristol, United Kingdom Sanjiv Banerjee, NRES Committee South Central–Berkshire, Bristol, United Kingdom Sara Vaz-Pereira, CEIC–Comissão de Ética para Investigação Clínica, Lisboa, Portugal Scott Oliver, Western Institutional Review Board, Puyallup, United States Scott Foxman, Quorum, Seattle, United States Sean Adrean, Quorum, Seattle, United States Sebastian Wolf, Kantonale Ethikkommission Bern KEK, Bern, Switzerland Silvio Lujan, CE para la Invest. Univ de San Martín de Porres, Lima, Peru Simona Esposti, NRES Committee South Central–Berkshire, Bristol, United Kingdom Subhransu K. Ray, Quorum, Seattle, United States Sunil Patel, Quorum, Seattle, United States Szilard Kiss, Weill Cornell Med Center IRB, New York, United States Theodore Leng, Stanford University Research Compliance Office, Palo Alto, United States Tim Jackson, NRES Committee South Central–Berkshire, Bristol, United Kingdom Ulrich Bartz-Schmidt, Ethik-Kommission der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen, Tübingen, Germany Ursula Schmidt-Erfurth, Ethikkommission der Universität Wien/AKH, Wien, Austria Valery Erichev, FSBI “Scientific Research Institute of Eye Diseases” of Russia Academy of Medical Sciences, Moscow, Russian Federation Virgil Alfaro, Quorum, Seattle, United States William Durant, Quorum, Seattle, United States Yevgeniy Shildkrot, University of Virginia Institutional Review Board for Health Sciences Research, Charlottesville, United States



eAppendix 2. Methods Compliance Chroma (ClinicalTrials.gov, NCT02247479) and Spectri (ClinicalTrials.gov, NCT02247531) were conducted in accordance with applicable local, state, and federal laws where the research was conducted. Studies conducted in the European Union or European Economic Area complied with the E.U. Clinical Trial Directive (2001/20/EC). Studies complied with U.S. Food and Drug Administration (FDA) regulations, and study participants in the United States provided Health Insurance Portability and Accountability Act (HIPAA) authorization. CFI-Profile Biomarker Status Patients were evaluated at screening for complement factor I (CFI)-profile biomarker status based on risk alleles at single nucleotide polymorphisms (SNPs) rs4698775 (CFI), rs429608 (C2/CFB), and rs1329428 (CFH) (eTable 2A). CFI-profile biomarker status was defined as (eTable 2B): CFI-profile biomarker-positive (CFI+): risk allele carriers of CFI who were also risk allele carriers at CFH and/or C2/CFB; and CFI-profile biomarker-negative (CFI−): non-carriers of the CFI risk allele or carriers of the CFI risk allele who were non-carriers of the risk alleles at both CFH and C2/CFB. The inclusion of CFH and C2/CFB SNPs in the definition of the CFI-profile was intended to ensure that CFI-profile biomarker-positive patients also carried some risk alleles at these other known alternative complement genes, similar to the CFI risk allele carrier patients in the lampalizumab phase 2 study. Upon completion of enrollment in the phase 3 studies, genotype analysis indicated that all CFI risk allele carrier patients in Chroma and Spectri were also risk allele carriers at CFH and/or C2/CFB. Masking Chroma and Spectri were double-masked, necessitating a minimum of 2 participating ophthalmologists at each site. Reading center graders and centralized medical monitors who reviewed reports of adverse events (AEs) were masked to treatment assignments. Visual acuity and imaging technicians were masked to treatment group assignments. Study participants and investigators who were involved in all study aspects, except delivering treatment or sham, were masked to treatment assignments. A treating ophthalmologist and a study coordinator at each site were not masked due to the nature of the intravitreal treatment or sham injection. If an AE occurred during the treatment or injection, the masked investigator assigned causality. Treatment Protocol: Intravitreal Injection or Sham Procedure Lampalizumab was provided as a lyophilized powder, for reconstitution to a final concentration of 100 mg/mL. Pre-injection preparation, performed by the treating ophthalmologist, included application of 2 drops of 5% povidone iodine ophthalmic solution, followed by 0.5% proparacaine hydrochloride applied to the planned injection site with a sterile, cotton-tipped applicator, and then subconjunctival injection of lidocaine hydrochloride ophthalmic solution for injection (without epinephrine). Intravitreal injections provided 10 mg of lampalizumab in a total volume of 100 µL. In the sham groups, the eye was prepped in a manner similar to lampalizumab groups to preserve masking, including subconjunctival anesthesia. However, instead of an actual intravitreal injection, only the hub of a syringe was placed against the planned injection site.

In all participant groups, intraocular pressure (IOP) was measured in the study eye at each study visit, both before and 30–50 minutes after treatment. For posttreatment IOP ≥10 mm Hg above pre-injection levels, IOP measurements were repeated 60–80 minutes post-injection.

If choroidal neovascularization (CNV) was identified after randomization and treatment was recommended, a ranibizumab 0.5-mg intravitreal injection was given first, followed by a clinical assessment (including IOP check) from the investigators, and then the separate preparation and subsequent lampalizumab injection or sham procedure. Based on clinical decision, the administration of the 2 products could be performed on separate clinic days. Study Assessments Images were taken of both eyes and forwarded to Doheny Image Reading Center (Los Angeles, CA) for evaluation at screening and specified visits using fundus autofluorescence (FAF) and near-infrared at weeks 24, 36, 48, 72, and 96; spectral-domain optical coherence tomography (SD-OCT) at weeks 24, 48, 72, and 96; and fundus photography and fluorescein angiography at weeks 48 and 96.

At each visit, certified personnel obtained best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, starting at 4 meters, before treatment administration. Low-luminance visual acuity (LLVA) was measured at day 1 and weeks 24, 48, 72, and 96, and Minnesota Low-vision Reading Test (MNRead) or Radner Reading Charts, Functional Reading Independence (FRI) Index, and 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were administered at day 1 and weeks 48



and 96. Mesopic microperimetry assessments were performed at selected sites in a subset of patients at screening, day 1, and weeks 24, 48, 72, and 96. Reading Center Methods and Grading for Geographic Atrophy Areas of decreased autofluorescence were quantified in blue-light FAF images using the semi-automated tool RegionFinder (Heidelberg Engineering, Heidelberg, Germany). On these images, graders selected a point or “seed” in an area of decreased autofluorescence corresponding with GA, and the software algorithm proposed an outlined region consisting of the selected seed and neighboring pixels with comparable darkness. Multiple seeds could be placed for multiple lesions. Graders refined the outlined area by adjusting the tolerance with which pixels were recruited into the region (“growth power”) and, if necessary, drew manual constraints to exclude areas. Graders co-registered infrared reflectance images with blue-light FAF images to guide the exclusion of areas of naturally reduced signal in spared foveae. The software automatically compensated for intra-subject visit imaging and scaling differences. Secondary Efficacy Outcomes Secondary efficacy outcomes, exploratory at week 48 with formal statistical testing planned at week 96, included mean change from baseline in BCVA, LLVA, binocular maximum reading speed as assessed by MNRead or Radner Charts, FRI Index, NEI VFQ-25 scores and, in a subset of participants, mean macular sensitivity and number of absolute scotomatous testing points assessed by mesopic microperimetry (Nidek MP-1, Japan). Sample Size Estimates Data from the 2 sham treatment arms were pooled for analysis. The sample size for each study was selected to achieve adequate power to detect a meaningful difference in the primary efficacy endpoint, mean change from baseline in GA lesion size at Week 48, between a given lampalizumab dosing arm and the pooled sham arm within each of the CFI+ and CFI- patient groups and to meet health authority requirements for the overall size of the safety database. At the time of the study design, sample size and power calculations used assumptions based on results from the Phase II Study CFD4870g (Mahalo, NCT01229215). For each study, a sample size of 188 CFI+ patients per lampalizumab treatment arm and 94 CFI+ patients per sham arm provided >95% power to detect a targeted difference of 1.45 mm2 (approximately 40% reduction relative to sham control) in the CFI+ patient population; and 124 CFI− patients per lampalizumab treatment arm and 62 CFI− patients per sham arm provided 80% power to detect a targeted difference of 0.66 mm2 (approximately 40% reduction relative to control) in the CFI- patient population (eTable 3). Calculations were based on 2-sided t-tests at the α = 0.0495 level with the assumption of 15% dropout by week 48. Hypothesis Testing Per the Statistical Analysis Plan, the prespecified hypothesis testing hierarchy for the primary endpoint was: (1) overall population: lampalizumab every 4 weeks (q4w) vs sham; (2) CFI+ population: lampalizumab q4w vs sham; (3) overall population: lampalizumab every 6 weeks (q6w) vs sham; and (4) CFI+ population: lampalizumab q6w vs sham. Each hypothesis was evaluated at a 2-sided α = 0.0496 level, to account for a 0.0001 nominal penalty for each of the 4 planned independent Data Monitoring Committee (iDMC) unmasked data reviews that occurred prior to the primary analysis. Testing for significance proceeded to a subsequent hypothesis only if all prior hypotheses were significant at α = 0.0496. Role of the Study Sponsor The study was designed by the sponsor in coordination with the Executive Advisory Committee and lead investigators. The sponsor was masked to all treatment assignments through the 48-week primary outcome analysis. Data analyses were performed by the sponsor. No interim efficacy analyses were performed by the sponsor. All serious and non-serious AEs of special interest were promptly evaluated by the sponsor, who was responsible for identifying and expeditiously communicating any possible new safety findings to investigators, institutional review boards, ethics committees, and applicable health authorities based on current legislation.



eAppendix 3. Results Sham and Lampalizumab Treatments In each study, there were 5 participants who did not receive study treatment (lampalizumab or sham). In the first 48 weeks of Chroma and Spectri, treated participants in the q4w arms received a mean (SD) of 11.8 (2.5) and 11.7 (2.8) sham or 11.5 (2.9) and 11.7 (2.5) lampalizumab injections out of a total 13 possible injections, with 80.9%, 81.9%, 76.8%, and 77.8% of patients, respectively, receiving ≥12 injections. Similarly, in the q6w arms of Chroma and Spectri, treated participants received a mean (SD) of 8.3 (1.7) and 8.5 (1.2) sham or 8.2 (1.8) and 8.4 (1.4) lampalizumab injections out of a total 9 possible injections, with 87.9%, 90.5%, 85.5%, and 88.9% of patients, respectively, receiving ≥8 injections.



eTable 1. Full Eligibility Criteria for Chroma and Spectri General Inclusion Criteria

Willingness and the ability to provide signed informed consent. Additionally, at U.S. sites, patients must provide Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws

Age ≥50 years For women of childbearing potential or men with female partners of childbearing

potential, abstinence or use of contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug

Ability and willingness to undertake all scheduled visits and assessments Valid CFI-profile biomarker result (i.e., CFI-profile biomarker-positive or CFI-profile

biomarker-negative) Concurrent Systemic Conditions Exclusion Criteria

Uncontrolled blood pressure (defined as systolic >180 mm Hg and/or diastolic >110 mm Hg while patient is sitting)

History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that contraindicates the use of lampalizumab or that might affect interpretation of the results of the study or that renders the patient at high risk of treatment complications

Treatment for active systemic or localized infection. The ongoing prophylactic use of antimicrobial therapy should be discussed with the Medical Monitor

Predisposition or history of increased risk of infection (i.e., history of splenectomy or chronic immunosuppression)

Active malignancy within past 12 months except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of <6 and a stable prostate-specific antigen (PSA) for >12 months

History of allergy to fluorescein that is not amenable to treatment History of a severe allergic reaction or anaphylactic reaction to a biologic agent or

known hypersensitivity to any component of the lampalizumab injection Inability to comply with study or follow-up procedures Inability to obtain CFP, FAF, and FA of sufficient quality to be analyzed and graded by

the central reading center Previous participation in any studies of investigational drugs within 3 months preceding

Day 1 (excluding vitamins and minerals) Requirement for continuous use of any prohibited medications/treatments Women who are pregnant or lactating or intending to become pregnant during the study

Study Eye Inclusion Criteria

BCVA letter score of ≥49 letters (Snellen equivalent of 20/100 or better) using ETDRS charts at starting distance of 4 m

o If BCVA letter score is ≥79 letters (Snellen equivalent of 20/25 or better), at least 1 GA lesion must be within 250 μm of the foveal center

Well-demarcated area(s) of GA secondary to AMD with no evidence of prior or active CNV

o The total GA lesion size must be ≥2.54 mm2 (≥1 DA) and ≤17.78 mm2 (≤7 DA) and must reside completely within the FAF imaging field (Field 2−30 degree image centered on the fovea)

o If GA is multifocal, at least 1 focal lesion must be ≥1.27 mm2 (≥0.5 DA) Presence of either banded or diffuse hyperautofluorescence adjacent to the area of GA Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality

fundus imaging Non-study Eye Inclusion Criteria

GA secondary to AMD with no evidence of prior or active CNV

Non-study Eye Non-functioning non-study eye defined as either:



Exclusion Criteria

BCVA of hand motion or worse OR No physical presence of non-study eye (i.e., monocular)

Ocular Conditions: Exclusion Criteria

Either eye: GA in either eye due to causes other than AMD (monogenetic macular dystrophies [e.g.,

Stargardt disease, cone rod dystrophy] or toxic maculopathies [e.g., chloroquine/hydroxychloroquine maculopathy])

Retinal pigment epithelium (RPE) tear that involves the macula Active uveitis and/or vitritis (grade trace or above) History of idiopathic or autoimmune-associated uveitis Active, infectious conjunctivitis, keratitis, scleritis, or endophthalmitis Proliferative diabetic retinopathy Prior or active CNV Central serous retinopathy History of recurrent infections or inflammatory ocular disease Previous participation in interventional clinical trials for GA or dry AMD (except of

vitamins and minerals) irrespective of the route of administration (ocular or systemic) Previous treatment with eculizumab, lampalizumab, fenretidine, or any other drugs for

GA or dry AMD treatment

Study eye only: History of vitrectomy surgery, submacular surgery, or any surgical intervention for AMD Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein

occlusion, and proliferative diabetic retinopathy Prior treatment with Visudyne®, external-beam radiation therapy (for intraocular

conditions), or transpupillary thermotherapy History of prophylactic subthreshold laser treatment for AMD Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-

angiogenic drugs, anti-complement agents, or device implantation). A single intraoperative administration of a corticosteroid during cataract surgery for cystoid macular edema prophylaxis at least 3 months prior to screening is permitted

Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could do either of the following:

o Require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition

o If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of BCVA during the study period

Current vitreous hemorrhage History of retinal detachment or macular hole (Stage 3 or 4) Previous violation of the posterior capsule unless it occurred as a result of yttrium

aluminum garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation

Aphakia or absence of the posterior capsule Spherical equivalent of the refractive error demonstrating >8 diopters of myopia

o For patients who have undergone prior refractive or cataract surgery, the preoperative refractive error should not have exceeded 8 diopters of myopia

Intraocular surgery (including cataract surgery) within 3 months preceding Day 1 Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥30 mm Hg despite

treatment with anti-glaucoma medication) History of glaucoma-filtering surgery History of corneal transplant

Microperimetry Substudy: Inclusion Criteria

Patients must meet all other eligibility criteria for study entry Microperimetry screening test criteria for eligibility:

o Must be able to detect fixation target o Total elapsed time to complete the 10-2 68-point exam is ≤30 min o Reliability Test ratio ≤20% (false-positive rate)



o Ability and willingness to undertake microperimetry assessment as determined by investigator

Microperimetry Substudy: Exclusion Criteria

Any exclusion criteria listed for the study entry Investigator determines that patient is unable to perform the test reliably (e.g., difficulty

sitting still against the supporting chinrest for >10 min; unable to physically operate the clicker or joystick; unable to follow the instructions for the test [i.e., cognitive impairment])

Abbreviations: AMD, age-related macular degeneration; BCVA, best-corrected visual acuity; CFI, complement factor I; CFP, color fundus photograph; CNV, choroidal neovascularization; DA, disc area; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, fluorescein angiogram; FAF, fundus autofluorescence; GA, geographic atrophy.



eTable 2. Complement Factor I (CFI)-Profile Biomarker Status Definition. (A) Risk Alleles Assessed in CFI, C2/CFB, and CFH; (B) Definition of Biomarker Status Using the CFI-Profile Test

A.

Valid cobas ® Test Results AMD Gene

Chr. No.

Tagging SNP

Risk Allele

Major Allele

Risk Homozygous Heterozygous

Non-risk Homozygous

CFI 4 rs4698775 G T rs4698775 GG

rs4698775 TG

rs4698775 TT

C2/CFB 6 rs429608 G G rs429608 GG

rs429608 GA

rs429608 AA

CFH 1 rs1329428 C C rs1329428 CC

rs1329428 CT

rs1329428 TT

B.

CFI CFH C2/CFB CFI-profile biomarker-positive

+ + + + + − + − +

CFI-profile biomarker- negative

+ − − − + + − + − − − + − − −

“+” indicates that the patient is a risk allele carrier (i.e., heterozygous or homozygous for the risk allele) and “−” indicates that the patient is a non-carrier of the risk allele. Abbreviations: AMD, age-related macular degeneration; SNP, single nucleotide polymorphism.



eTable 3. Power and Minimum Detectable Difference for the Primary End Point for Each of Chroma and Spectri Two-sided α = 0.0495 Endpoint Target Treatment Effect Power MDD Mean change from baseline in GA area at 48 weeks in biomarker-positive patients (n=188 per arm)

∆ = 1.45 mm2 (approximately 40% a reduction) SD = 2.51

>95% 0.56 mm2 (approximately

15% a reduction)

Mean change from baseline in GA area at 48 weeks in biomarker-negative patients (n=124 per arm)

∆ = 0.66 mm2 (approximately 40% a reduction) SD = 1.68

80% 0.46 mm2 (approximately

28% a reduction)

The sample size takes into account the dropout rate of 15% by 1 year. The power and MDD are for each comparison between 1 lampalizumab treatment group and the pooled sham group. Abbreviations: GA, geographic atrophy; MDD, minimum detectable difference. a Relative to the sham group and assuming the mean change from baseline in GA area at 48 weeks is 1.645 mm2 for biomarker-negative group and 3.631 mm2 for biomarker-positive group (per the Phase II Study CFD4870g [Mahalo, NCT01229215]).



eTable 4. Participant Demographics and Baseline Characteristics in Chroma Sham Lampalizumab 10 mg All

Patients (N=906)

q4w (n=153)

q6w (n=152)

Pooled (n=305)

q4w (n=298)

q6w (n=303)

Participant Demographics Age, years, mean (SD) 78.6 (7.8) 78.5 (7.8) 78.5 (7.8) 77.5 (7.9) 78.3 (8.5) 78.1 (8.1)

Median 79 78 79 78 79 79 Range 51 - 94 53 - 95 51 - 95 51 - 95 54 - 96 51 - 96

Sex, No. (%) Male 61

(39.9%) 58

(38.2%) 119

(39.0%) 116

(38.9%) 118

(38.9%) 353

(39.0%) Female 92

(60.1%) 94

(61.8%) 186

(61.0%) 182

(61.1%) 185

(61.1%) 553

(61.0%) Race, No. (%)

American Indian or Alaskan Native 0 0 0 2 (0.7%) 1 (0.3%) 3 (0.3%) Asian 0 0 0 0 0 0 Black or African American 0 0 0 0 0 0 Native Hawaiian or other Pacific Islander 0 0 0 1 (0.3%) 0 1 (0.1%) White 150

(98.0%) 152

(100%) 302

(99.0%) 293

(98.3%) 295

(97.4%) 890

(98.2%) Multiple 0 0 0 0 1 (0.3%) 1 (0.1%) Unknown 3 (2.0%) 0 3 (1.0%) 2 (0.7%) 6 (2.0%) 11 (1.2%)

Tobacco use, No. (%) Never 76

(49.7%) 58

(38.2%) 134

(43.9%) 141

(47.3%) 129

(42.6%) 404

(44.6%) Previous 70

(45.8%) 83

(54.6%) 153

(50.2%) 141

(47.3%) 154

(50.8%) 448

(49.4%) Current 7 (4.6%) 11 (7.2%) 18 (5.9%) 16 (5.4%) 20 (6.6%) 54 (6.0%)

Study Eye Baseline Characteristics

GA area a, mm2, mean (SD) 7.904

(4.086) 8.004

(3.769) 7.953

(3.925) 7.910

(3.887) 8.116

(4.236) 7.993

(4.016) Median 6.830 7.145 6.990 7.215 7.050 7.100

Range 1.58 - 17.56

2.72 - 17.77

1.58 - 17.77

2.54 - 17.71

2.29 - 22.19

1.58 - 22.19

GA lesion contiguity a, No. (%)

Multifocal 120

(78.4%) 124

(81.6%) 244

(80.0%) 232

(77.9%) 231

(76.5%) 707

(78.1%)

Non-multifocal 33

(21.6%) 28

(18.4%) 61

(20.0%) 66

(22.1%) 71

(23.5%) 198

(21.9%) GA lesion location a,b, No. (%)

Subfoveal 86

(56.2%) 72

(47.4%) 158

(51.8%) 154

(51.7%) 146

(48.3%) 458

(50.6%)

Non-subfoveal 67

(43.8%) 80

(52.6%) 147

(48.2%) 144

(48.3%) 156

(51.7%) 447

(49.4%) Hyperautofluorescence pattern, No. (%)

Banded 5 (3.3%) 5 (3.3%) 10 (3.3%) 8 (2.7%) 15 (5.0%) 33 (3.6%)

Diffuse 148

(96.7%) 147

(96.7%) 295

(96.7%) 289

(97.0%) 288

(95.0%) 872

(96.2%) Not applicable 0 0 0 1 (0.3%) 0 1 (0.1%)

BCVA c, letter score, mean (SD) 66.3

(10.0) 65.4 (9.9) 65.9 (9.9) 66.1

(10.0) 66.4

(10.1) 66.2 (10.0)



Sham Lampalizumab 10 mg All Patients (N=906)

q4w (n=153)

q6w (n=152)

Pooled (n=305)

q4w (n=298)

q6w (n=303)

<64 (worse than 20/50) 56

(37.1%) 60

(40.0%) 116

(38.5%) 117

(39.7%) 118

(39.2%) 351

(39.1%)

≥64 (20/50 or better) 95

(62.9%) 90

(60.0%) 185

(61.5%) 178

(60.3%) 183

(60.8%) 546

(60.9%)

LLVA, letter score, mean (SD) d 36.4

(15.4) 35.6

(16.1) 36.0

(15.7) 36.9

(17.8) 36.2

(16.7) 36.4 (16.7)

LLD (BCVA-LLVA), letter score, mean (SD) e

29.8 (16.4)

29.7 (15.2)

29.8 (15.8)

29.1 (17.0)

30.4 (15.8)

29.8 (16.2)

Abbreviations: BCVA, best-corrected visual acuity; GA, geographic atrophy; LLD, low-luminance deficit; LLVA, low-luminance visual acuity; q4w, every 4 weeks; q6w, every 6 weeks. a For lampalizumab q6w, n=302. b GA lesion location of subfoveal was defined as a GA lesion involving the foveal center point. c For BCVA, sham q4w: n=151, sham q6w: n=150, lampalizumab q4w: n=295, lampalizumab q6w: n=301. d For LLVA, sham q4w: n=149, sham q6w: n=150, lampalizumab q4w: n=287, lampalizumab q6w: n=293. e For LLD, sham q4w: n=148, sham q6w: n=149, lampalizumab q4w: n=287, lampalizumab q6w: n=293.



eTable 5. Participant Demographics and Baseline Characteristics in Spectri Sham Lampalizumab 10 mg

q4w (n=161)

q6w

(n=160)

Pooled (n=321)

q4w

(n=330)

q6w

(n=324)

All Patients (N=975)

Participant Demographics Age, years, mean (SD) 77.7 (8.4) 77.5 (8.1) 77.6 (8.3) 77.3 (7.9) 78.7 (8.0) 77.9 (8.1)

Median 78 78 78 78 80 78 Range 55 - 96 51 - 95 51 - 96 50 - 94 53 - 97 50 - 97

Sex, No. (%) Male 66

(41.0%) 64

(40.0%) 130

(40.5%) 133

(40.3%) 134

(41.4%) 397

(40.7%) Female 95

(59.0%) 96

(60.0%) 191

(59.5%) 197

(59.7%) 190

(58.6%) 578

(59.3%) Race, No. (%)

American Indian or Alaskan Native 0 2 (1.3%) 2 (0.6%) 3 (0.9%) 1 (0.3%) 6 (0.6%) Asian 0 3 (1.9%) 3 (0.9%) 1 (0.3%) 1 (0.3%) 5 (0.5%) Black or African American 0 0 0 1 (0.3%) 0 1 (0.1%) Native Hawaiian or other Pacific Islander 1 (0.6%) 0 1 (0.3%) 0 0 1 (0.1%) White 156

(96.9%) 150

(93.8%) 306

(95.3%) 315

(95.5%) 316

(97.5%) 937

(96.1%) Multiple 0 2 (1.3%) 2 (0.6%) 0 1 (0.3%) 3 (0.3%) Unknown 4 (2.5%) 3 (1.9%) 7 (2.2%) 10 (3.0%) 5 (1.5%) 22 (2.3%)

Tobacco use, No. (%) Never 77

(47.8%) 78

(48.8%) 155

(48.3%) 152

(46.1%) 161

(49.7%) 468

(48.0%) Previous 77

(47.8%) 72

(45.0%) 149

(46.4%) 154

(46.7%) 141

(43.5%) 444

(45.5%) Current 7 (4.3%) 10 (6.3%) 17 (5.3%) 24 (7.3%) 22 (6.8%) 63 (6.5%)

Study Eye Baseline Characteristics

GA area, mm2, mean (SD) 7.227

(3.664) 7.883

(4.266) 7.554

(3.983) 8.308

(3.916) 8.498

(4.260) 8.123

(4.071) Median 6.350 6.685 6.470 7.490 7.915 7.320

Range 2.55 - 17.13

2.61 - 30.56

2.55 - 30.56

2.55 - 17.74

2.54 - 17.70

2.54 - 30.56

GA lesion contiguity, No. (%)

Multifocal 118

(73.3%) 129

(80.6%) 247

(76.9%) 264

(80.0%) 246

(75.9%) 757

(77.6%)

Non-multifocal 43

(26.7%) 31

(19.4%) 74

(23.1%) 66

(20.0%) 78

(24.1%) 218

(22.4%) GA lesion location a, No. (%)

Subfoveal 86

(53.4%) 94

(58.8%) 180

(56.1%) 175

(53.0%) 174

(53.7%) 529

(54.3%)

Non-subfoveal 75

(46.6%) 66

(41.3%) 141

(43.9%) 155

(47.0%) 150

(46.3%) 446

(45.7%) Hyperautofluorescence pattern, No. (%)

Banded 7 (4.3%) 6 (3.8%) 13 (4.0%) 14 (4.2%) 20 (6.2%) 47 (4.8%)

Diffuse 153

(95.0%) 154

(96.3%) 307

(95.6%) 316

(95.8%) 303

(93.5%) 926

(95.0%) Not applicable 1 (0.6%) 0 1 (0.3%) 0 1 (0.3%) 2 (0.2%)

BCVA, letter score, mean (SD) b 66.5 65.8 (9.4) 66.1 (9.8) 66.0 (9.6) 65.7 (9.8) 66.0 (9.7)



Sham Lampalizumab 10 mg

q4w (n=161)

q6w

(n=160)

Pooled (n=321)

q4w

(n=330)

q6w

(n=324)

All Patients (N=975)

(10.1)

<64 (worse than 20/50) 59

(36.9%) 58

(36.5%) 117

(36.7%) 136

(41.2%) 129

(40.2%) 382

(39.4%)

≥64 (20/50 or better) 101

(63.1%) 101

(63.5%) 202

(63.3%) 194

(58.8%) 192

(59.8%) 588

(60.6%)

LLVA, letter score, mean (SD) c 36.8

(16.7) 36.8

(16.5) 36.8

(16.5) 36.1

(17.5) 35.8

(16.8) 36.2 (16.9) LLD (BCVA-LLVA), letter score, mean (SD) c

29.8 (15.9)

28.9 (16.7)

29.4 (16.3)

29.9 (15.6)

29.8 (15.7) 29.7 (15.8)

Abbreviations: BCVA, best-corrected visual acuity; GA, geographic atrophy; LLD, low-luminance deficit; LLVA, low-luminance visual acuity; q4w, every 4 weeks; q6w, every 6 weeks. a GA lesion location of subfoveal was defined as a GA lesion involving the foveal center point. b For BCVA, sham q4w: n=160, sham q6w: n=159, lampalizumab q4w: n=330, lampalizumab q6w: n=321. c For LLVA and LLD, sham q4w: n=155, sham q6w: n=155, lampalizumab q4w: n=322, lampalizumab q6w: n=310.



eTable 6. Week 48 Outcomes in Chroma, Intent-to-Treat Population Sham

Pooled (n=292)

Lampalizumab 10 mg q4w

(n=279)


(n=287) Primary Endpoint: Change From Baseline in GA Area at Week 48 (mm2) Adjusted mean (SE) 2.041 (0.066) 2.017 (0.068) 2.091 (0.067) Difference in means (vs sham pooled) –0.024 0.05

95% CI (–0.210-0.162) (–0.135-0.235) Relative reduction 1.2% –2.5% P value .80 .59

Rate of Change in GA Area (Growth Slope) From Baseline to Week 48 (mm2/365.25 days) a Adjusted mean slope (SE) 2.061 (0.069) 2.036 (0.071) 2.130 (0.070) Difference in slopes (vs sham pooled) –0.024 0.070


Change From Baseline in Square Root of GA Area at Week 48 (mm) Adjusted mean (SE) 0.347 (0.011) 0.344 (0.011) 0.364 (0.011) Difference in means (vs sham pooled) –0.003 0.017


Percent Change From Baseline in GA Area at Week 48 (%) Adjusted mean (SE) 29.954 (1.282) 29.486 (1.313) 32.676 (1.294) Difference in means (vs sham pooled) –0.468 2.722


Sample sizes shown in headers are the number of patients included in the mixed effect model repeated measures (MMRM) analysis. All P values are 2-sided and calculated for the difference between means (lampalizumab minus sham). Abbreviations: GA, geographic atrophy; q4w, every 4 weeks; q6w, every 6 weeks. a For Growth Slope MMRM analysis, sham pooled: n=305, lampalizumab q4w: n=298, lampalizumab q6w: n=302.



eTable 7. Week 48 Outcomes in Spectri, Intent-to-Treat Population Sham

Pooled (n=306)


(n=317)


(n=316) Primary Endpoint: Change From Baseline in GA Area at Week 48 (mm2) Adjusted mean (SE) 1.932 (0.056) 2.089 (0.056) 2.019 (0.056) Difference in means (vs sham pooled) 0.157 0.087

95% CI (0.001-0.313) (–0.069-0.243) Relative reduction –8.1% –4.5% P value .048 .27

Rate of Change in GA Area (Growth Slope) From Baseline to Week 48 (mm2/365.25 days) a Adjusted mean slope (SE) 1.939 (0.059) 2.111 (0.058) 2.043 (0.058) Difference in slopes (vs sham pooled) 0.172 0.104

95% CI (0.009-0.335) (–0.059-0.267) Relative reduction –8.9% –5.4% P value .038 .21

Change From Baseline in Square Root of GA Area at Week 48 (mm) Adjusted mean (SE) 0.338 (0.009) 0.352 (0.009) 0.341 (0.009) Difference in means (vs sham pooled) 0.014 0.003

95% CI (–0.011-0.040) (–0.023-0.028) Relative reduction –4.2% –0.9% P value .28 .82

Percent Change From Baseline in GA Area at Week 48 (%) Adjusted mean (SE) 30.131 (1.143) 29.577 (1.125) 29.111 (1.126) Difference in means (vs sham pooled) –0.555 –1.021

95% CI (–3.702-2.592) (–4.169-2.128) Relative reduction 1.8% 3.4% P value .73 .52

Sample sizes shown in headers are the number of patients included in the mixed effect model repeated measures (MMRM) analysis. All P values are 2-sided and calculated for the difference between means (lampalizumab minus sham). Abbreviations: GA, geographic atrophy; q4w, every 4 weeks; q6w, every 6 weeks. a For Growth Slope MMRM analysis, sham pooled: n=321, lampalizumab q4w: n=330, lampalizumab q6w: n=324.



eTable 8. Geographic Atrophy Area Change from Baseline to Week 48 by CFI-Profile Biomarker Status, for Chroma and Spectri, Pooled and Separate CFI+ CFI− Change From Baseline in GA Area at Week 48 (mm2)

Sham Pooled



Sham Pooled



Pooled Chroma and Spectri N 360 358 359 238 238 244 Adjusted mean (SE)

2.035 (0.056) 2.053 (0.057) 2.088 (0.057)

1.908 (0.067) 2.061 (0.068) 2.003 (0.067)

Difference in means (vs sham pooled) 0.018 0.053 0.152 0.094

95% CI (–0.139-0.175) (–0.104-0.209) (–0.036-0.340) (–0.092-0.281) Relative reduction –0.9% –2.6% –8.0% –4.90 P value .82 .51 .11 .32

Chroma N 174 163 170 118 116 117 Adjusted mean (SE)

2.067 (0.086) 2.045 (0.089) 2.144 (0.087)

2.006 (0.103) 1.974 (0.105) 2.012 (0.104)

Difference in means (vs sham pooled) –0.022 0.077 –0.033 0.006

95% CI (–0.266-0.223) (–0.165-0.319) (–0.322-0.257) (–0.283-0.294) Relative reduction 1.1% –3.7% 1.6% –0.3% P value .86 .53 .82 .97

Spectri N 186 195 189 120 122 127 Adjusted mean (SE)

2.007 (0.074) 2.057 (0.072) 2.032 (0.073)

1.809 (0.087) 2.149 (0.087) 1.991 (0.085)

Difference in means (vs sham pooled) 0.049 0.025 0.340 0.182

95% CI (–0.153-0.252) (–0.180-0.230) (0.097, 0.584) (–0.058-0.422) Relative reduction –2.5% –1.2% –18.8% –10.1% P value .63 .81 .0063 .14

Mixed effect model repeated measures (MMRM) analysis, by biomarker group, adjusted for baseline geographic atrophy area, subfoveal vs non-subfoveal location, and multifocal vs non-multifocal configuration; baseline best-corrected visual acuity category; and sex. The pooled analysis included an additional covariate adjustment for study. Sample sizes are the number of patients included in the MMRM analysis. All P values are 2-sided and calculated for the difference between means (lampalizumab minus sham). P values not adjusted for multiplicity. Abbreviations: CFI, complement factor I; GA, geographic atrophy; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 9. Best-Corrected Visual Acuity Change From Baseline at Week 48 Change From Baseline in BCVA at Week 48 (letter score)

Sham

Pooled

Lampalizumab 10 mg

q4w

Lampalizumab 10 mg

q6w Pooled Chroma and Spectri N 604 601 604 Adjusted mean (SE) –4.9 (0.5) –4.1 (0.5) –4.9 (0.5) Difference in means (vs sham pooled) 0.8 0.1

95% CI (–0.4-2.1) (–1.2-1.3) P value .20 .94

Chroma N 294 280 288 Adjusted mean (SE) –4.5 (0.6) –3.4 (0.6) –4.6 (0.6) Difference in means (vs sham pooled) 1.0 –0.2

95% CI (–0.7-2.8) (–1.9-1.6) P value .25 .84

Spectri N 310 321 316 Adjusted mean (SE) –5.3 (0.7) –4.6 (0.7) –5.1 (0.7) Difference in means (vs sham pooled) 0.7 0.3

95% CI (–1.2-2.5) (–1.6-2.1) P value .46 .79

Mixed effect model repeated measures (MMRM) analysis adjusted for baseline BCVA, baseline geographic atrophy lesion location, biomarker status, and sex. The pooled analysis included an additional covariate adjustment for study. Sample sizes are the number of patients included in the MMRM analysis. All P values are 2-sided and calculated for the difference between means (lampalizumab minus sham). Abbreviations: BCVA, best-corrected visual acuity; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 10. Adverse Event Overview, Ocular and Non-Ocular, First 48 Weeks, Chroma and Spectri Pooled

Sham Lampalizumab 10 mg q4w q6w Pooled q4w q6w Pooled (n=312) (n=307) (n=619) (n=626) (n=626) (N=1252)

Ocular Adverse Events: Study Eye Total number of ocular AEs 473 396 869 1451 1130 2581 Total number of ocular SAEs 12 6 18 64 58 122 No. (%) of patients with at least 1:

Ocular AE 170

(54.5%) 153

(49.8%) 323

(52.2%) 400

(63.9%) 365

(58.3%) 765

(61.1%) Ocular AE suspected to be caused by study drug per investigator

17 (5.4%)

11 (3.6%)

28 (4.5%)

77 (12.3%)

59 (9.4%)

136 (10.9%)

Ocular AE leading to treatment discontinuation 4 (1.3%) 0 4 (0.6%) 7 (1.1%) 8 (1.3%) 15 (1.2%)

Ocular SAE 12

(3.8%) 5 (1.6%) 17

(2.7%) 39

(6.2%) 38

(6.1%) 77 (6.2%) Ocular SAE suspected to be caused by study drug per investigator 0 0 0

16 (2.6%)

11 (1.8%) 27 (2.2%)

Ocular SAE leading to treatment discontinuation 2 (0.6%) 0 2 (0.3%) 6 (1.0%) 7 (1.1%) 13 (1.0%) Ocular AE of special interest: Sight-threatening AE 9 (2.9%) 5 (1.6%)

14 (2.3%)

38 (6.1%)

31 (5.0%) 69 (5.5%)

Ocular Adverse Events: Fellow Eye Total number of ocular AEs 141 143 284 335 259 594 Total number of ocular SAEs 6 2 8 12 12 24 No. (%) of patients with at least 1:

Ocular AE 86

(27.6%) 89

(29.0%) 175

(28.3%) 213

(34.0%) 171

(27.3%) 384

(30.7%) Ocular AE suspected to be caused by study drug per investigator 0 0 0 0 1 (0.2%) 1 (<0.1%) Ocular AE leading to treatment discontinuation 0 0 0 0 1 (0.2%) 1 (<0.1%)

Ocular SAE 5 (1.6%) 2 (0.7%) 7 (1.1%) 12

(1.9%) 11

(1.8%) 23 (1.8%) Ocular SAE suspected to be caused by study drug per investigator 0 0 0 0 0 0 Ocular SAE leading to treatment discontinuation 0 0 0 0 0 0 Ocular AE of special interest: Sight-threatening AE 5 (1.6%) 2 (0.7%) 7 (1.1%)

10 (1.6%)

11 (1.8%) 21 (1.7%)

Non-Ocular Adverse Events Total number of non-ocular AEs 710 678 1388 1726 1236 2962 Total number of non-ocular SAEs 84 74 158 212 143 355 No. (%) of deaths 4 (1.3%) 3 (1.0%) 7 (1.1%) 7 (1.1%) 5 (0.8%) 12 (1.0%) No. (%) of patients with at least 1:

Non-ocular AE 219

(70.2%) 203

(66.1%) 422

(68.2%) 457

(73.0%) 396

(63.3%) 853

(68.1%) Non-ocular AE suspected to be caused by study drug per investigator 1 (0.3%) 1 (0.3%) 2 (0.3%) 2 (0.3%) 3 (0.5%) 5 (0.4%) Non-ocular AE leading to treatment discontinuation 9 (2.9%) 3 (1.0%)

12 (1.9%)

10 (1.6%)

10 (1.6%) 20 (1.6%)



Sham Lampalizumab 10 mg q4w q6w Pooled q4w q6w Pooled (n=312) (n=307) (n=619) (n=626) (n=626) (N=1252)

Non-ocular SAE 49

(15.7%) 54

(17.6%) 103

(16.6%) 120

(19.2%) 87

(13.9%) 207

(16.5%) Non-ocular SAE suspected to be caused by study drug per investigator 0 0 0 1 (0.2%) 0 1 (<0.1%) SAE leading to treatment discontinuation 7 (2.2%) 1 (0.3%) 8 (1.3%) 9 (1.4%) 8 (1.3%) 17 (1.4%)

Investigator text for AEs coded using Medical Dictionary for Regulatory Activities version 20.0. Percentages are based on the N in the column headings. Table summary includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study. Multiple occurrences of the same AE in 1 individual are counted only once except for rows of "Number of ocular AEs" and "Number of non-ocular AEs" in which multiple occurrences of the same AE are counted separately. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; q4w, every 4 weeks; q6w, every 6 weeks; SAE, serious adverse event.



eTable 11. Ocular Adverse Events in the Study Eye Occurring in ≥1% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg

MedDRA Preferred Term q4w

(n=312)

q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total No. (%) of patients with any ocular AE

170 (54.5%)

153 (49.8%)

323 (52.2%)

400 (63.9%)

365 (58.3%)

765 (61.1%)

CONJUNCTIVAL HAEMORRHAGE 76

(24.4%) 75

(24.4%) 151

(24.4%) 208

(33.2%) 163

(26.0%) 371

(29.6%) INTRAOCULAR PRESSURE INCREASED 4 (1.3%) 6 (2.0%)

10 (1.6%)

83 (13.3%)

58 (9.3%)

141 (11.3%)

EYE PAIN 22

(7.1%) 13

(4.2%) 35

(5.7%) 71

(11.3%) 54

(8.6%) 125 (10%)

VITREOUS FLOATERS 7 (2.2%) 7 (2.3%) 14

(2.3%) 49

(7.8%) 39

(6.2%) 88 (7.0%)

VITREOUS DETACHMENT 18

(5.8%) 9 (2.9%) 27

(4.4%) 34

(5.4%) 33

(5.3%) 67 (5.4%)

DRY EYE 17

(5.4%) 8 (2.6%) 25

(4.0%) 26

(4.2%) 19

(3.0%) 45 (3.6%)

CATARACT 9 (2.9%) 8 (2.6%) 17

(2.7%) 25

(4.0%) 20

(3.2%) 45 (3.6%)

EYE IRRITATION 11

(3.5%) 9 (2.9%) 20

(3.2%) 17

(2.7%) 23

(3.7%) 40 (3.2%)

PUNCTATE KERATITIS 9 (2.9%) 7 (2.3%) 16

(2.6%) 18

(2.9%) 22

(3.5%) 40 (3.2%)

BLEPHARITIS 6 (1.9%) 8 (2.6%) 14

(2.3%) 24

(3.8%) 13

(2.1%) 37 (3.0%)

VISION BLURRED 13

(4.2%) 7 (2.3%) 20

(3.2%) 19

(3.0%) 15

(2.4%) 34 (2.7%)

LACRIMATION INCREASED 6 (1.9%) 7 (2.3%) 13

(2.1%) 20

(3.2%) 12

(1.9%) 32 (2.6%)

RETINAL HAEMORRHAGE 4 (1.3%) 5 (1.6%) 9 (1.5%) 14

(2.2%) 14

(2.2%) 28 (2.2%) POSTERIOR CAPSULE OPACIFICATION 3 (1.0%) 2 (0.7%) 5 (0.8%)

19 (3.0%) 9 (1.4%) 28 (2.2%)

VISUAL ACUITY REDUCED 7 (2.2%) 5 (1.6%) 12

(1.9%) 11

(1.8%) 14

(2.2%) 25 (2.0%)

SENSATION OF FOREIGN BODY 7 (2.2%) 6 (2.0%) 13

(2.1%) 16

(2.6%) 7 (1.1%) 23 (1.8%) FOREIGN BODY SENSATION IN EYES 5 (1.6%) 6 (2.0%)

11 (1.8%)

11 (1.8%)

11 (1.8%) 22 (1.8%)

CORNEAL ABRASION 8 (2.6%) 1 (0.3%) 9 (1.5%) 11

(1.8%) 11

(1.8%) 22 (1.8%)

OCULAR HYPERAEMIA 3 (1.0%) 6 (2.0%) 9 (1.5%) 12

(1.9%) 9 (1.4%) 21 (1.7%)

CONJUNCTIVAL HYPERAEMIA 5 (1.6%) 3 (1.0%) 8 (1.3%) 9 (1.4%) 12

(1.9%) 21 (1.7%)

VISUAL IMPAIRMENT 4 (1.3%) 4 (1.3%) 8 (1.3%) 9 (1.4%) 11

(1.8%) 20 (1.6%) OCULAR DISCOMFORT 4 (1.3%) 2 (0.7%) 6 (1.0%) 9 (1.4%) 9 (1.4%) 18 (1.4%) VISUAL ACUITY REDUCED TRANSIENTLY 0 1 (0.3%) 1 (0.2%) 9 (1.4%) 9 (1.4%) 18 (1.4%)

CONJUNCTIVITIS 1 (0.3%) 7 (2.3%) 8 (1.3%) 15

(2.4%) 3 (0.5%) 18 (1.4%)





(n=312)

q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

EYELID OEDEMA 2 (0.6%) 4 (1.3%) 6 (1.0%) 4 (0.6%) 13

(2.1%) 17 (1.4%) PHOTOPSIA 4 (1.3%) 1 (0.3%) 5 (0.8%) 8 (1.3%) 7 (1.1%) 15 (1.2%) NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 3 (1.0%) 1 (0.3%) 4 (0.6%) 6 (1.0%) 9 (1.4%) 15 (1.2%) BLINDNESS TRANSIENT 0 0 0 8 (1.3%) 7 (1.1%) 15 (1.2%) CORNEAL EROSION 4 (1.3%) 3 (1.0%) 7 (1.1%) 8 (1.3%) 4 (0.6%) 12 (1.0%) EYE DISCHARGE 2 (0.6%) 2 (0.7%) 4 (0.6%) 6 (1.0%) 6 (1.0%) 12 (1.0%) BURNING SENSATION 1 (0.3%) 2 (0.7%) 3 (0.5%) 6 (1.0%) 5 (0.8%) 11 (0.9%) PHOTOPHOBIA 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 5 (0.8%) 11 (0.9%) VITREOUS HAEMORRHAGE 0 1 (0.3%) 1 (0.2%) 6 (1.0%) 4 (0.6%) 10 (0.8%) EYE PRURITUS 4 (1.3%) 7 (2.3%) 11(1.8%) 8 (1.3%) 2 (0.3%) 10 (0.8%) PAIN 4 (1.3%) 2 (0.7%) 6 (1.0%) 8 (1.3%) 2 (0.3%) 10 (0.8%) CHOROIDAL NEOVASCULARISATION 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 3 (0.5%) 9 (0.7%) ERYTHEMA 1 (0.3%) 2 (0.7%) 3 (0.5%) 6 (1.0%) 2 (0.3%) 8 (0.6%) VITREOUS DISORDER 1 (0.3%) 0 1 (0.2%) 6 (1.0%) 1 (0.2%) 7 (0.6%) INJECTION SITE PAIN 2 (0.6%) 3 (1.0%) 5 (0.8%) 4 (0.6%) 2 (0.3%) 6 (0.5%) RETINAL DEGENERATION 3 (1.0%) 0 3 (0.5%) 1 (0.2%) 2 (0.3%) 3 (0.2%) VITAL DYE STAINING CORNEA PRESENT 0 3 (1.0%) 3 (0.5%) 2 (0.3%) 0 2 (0.2%) EYELIDS PRURITUS 3 (1.0%) 0 3 (0.5%) 0 1 (0.2%) 1 (<0.1%) Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on N in the column headings. For frequency counts by preferred term, multiple occurrences of the same AE in an individual are counted only once. Table includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study in ≥1% of patients in any treatment group. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 12. Non-Ocular Adverse Events Occurring in ≥1% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled



(n=312) q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total No. (%) of patients with any non-ocular AE

219 (70.2%)

203 (66.1%)

422 (68.2%)

457 (73.0%)

396 (63.3%) 853 (68.1%)

VIRAL UPPER RESPIRATORY TRACT INFECTION 30 (9.6%) 19 (6.2%) 49 (7.9%)

61 (9.7%)

47 (7.5%) 108 (8.6%)

FALL 32 (10.3%) 20 (6.5%) 52 (8.4%) 51

(8.1%) 40

(6.4%) 91 (7.3%)

BRONCHITIS 15 (4.8%) 10 (3.3%) 25 (4.0%) 34

(5.4%) 35

(5.6%) 69 (5.5%)

URINARY TRACT INFECTION 18 (5.8%) 15 (4.9%) 33 (5.3%) 41

(6.5%) 20

(3.2%) 61 (4.9%)

HYPERTENSION 14 (4.5%) 10 (3.3%) 24 (3.9%) 29

(4.6%) 23

(3.7%) 52 (4.2%)

HEADACHE 13 (4.2%) 0 13 (2.1%) 28

(4.5%) 16

(2.6%) 44 (3.5%)

INFLUENZA 8 (2.6%) 11 (3.6%) 19 (3.1%) 26

(4.2%) 16

(2.6%) 42 (3.4%)

ARTHRALGIA 7 (2.2%) 14 (4.6%) 21 (3.4%) 26

(4.2%) 17

(2.7%) 43 (3.4%) UPPER RESPIRATORY TRACT INFECTION 17 (5.4%) 8 (2.6%) 25 (4.0%)

24 (3.8%)

17 (2.7%) 41 (3.3%)

COUGH 4 (1.3%) 5 (1.6%) 9 (1.5%) 26

(4.2%) 14

(2.2%) 40 (3.2%)

BACK PAIN 12 (3.8%) 18 (5.9%) 30 (4.8%) 23

(3.7%) 14

(2.2%) 37 (3.0%) CHRONIC OBSTRUCTIVE PULMONARY DISEASE 1 (0.3%) 4 (1.3%) 5 (0.8%)

21 (3.4%)

14 (2.2%) 35 (2.8%)

DIARRHOEA 7 (2.2%) 4 (1.3%) 11 (1.8%) 19

(3.0%) 10

(1.6%) 29 (2.3%)

PNEUMONIA 10 (3.2%) 9 (2.9%) 19 (3.1%) 18

(2.9%) 10

(1.6%) 28 (2.2%)

ATRIAL FIBRILLATION 7 (2.2%) 8 (2.6%) 15 (2.4%) 13

(2.1%) 13

(2.1%) 26 (2.1%)

CONTUSION 3 (1.0%) 10 (3.3%) 13 (2.1%) 17

(2.7%) 9 (1.4%) 26 (2.1%)

CONSTIPATION 5 (1.6%) 1 (0.3%) 6 (1.0%) 13

(2.1%) 11

(1.8%) 24 (1.9%)

SINUSITIS 7 (2.2%) 8 (2.6%) 15 (2.4%) 16

(2.6%) 8 (1.3%) 24 (1.9%)

OSTEOARTHRITIS 9 (2.9%) 6 (2.0%) 15 (2.4%) 16

(2.6%) 8 (1.3%) 24 (1.9%)

DEPRESSION 7 (2.2%) 11 (3.6%) 18 (2.9%) 12

(1.9%) 12

(1.9%) 24 (1.9%) GASTROOESOPHAGEAL REFLUX DISEASE 4 (1.3%) 6 (2.0%) 10 (1.6%)

15 (2.4%) 5 (0.8%) 20 (1.6%)

NAUSEA 6 (1.9%) 6 (2.0%) 12 (1.9%) 12

(1.9%) 7 (1.1%) 19 (1.5%)

PAIN IN EXTREMITY 4 (1.3%) 3 (1.0%) 7 (1.1%) 8 (1.3%) 11

(1.8%) 19 (1.5%)

ANXIETY 1 (0.3%) 5 (1.6%) 6 (1.0%) 14

(2.2%) 5 (0.8%) 19 (1.5%)





(n=312) q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

ANAEMIA 0 8 (2.6%) 8 (1.3%) 11

(1.8%) 7 (1.1%) 18 (1.4%) DIZZINESS 5 (1.6%) 7 (2.3%) 12 (1.9%) 9 (1.4%) 9 (1.4%) 18 (1.4%) SEASONAL ALLERGY 4 (1.3%) 2 (0.7%) 6 (1.0%) 8 (1.3%) 9 (1.4%) 17 (1.4%) MUSCLE SPASMS 4 (1.3%) 1 (0.3%) 5 (0.8%) 8 (1.3%) 9 (1.4%) 17 (1.4%)

SCIATICA 8 (2.6%) 6 (2.0%) 14 (2.3%) 14

(2.2%) 3 (0.5%) 17 (1.4%) CARDIAC FAILURE CONGESTIVE 3 (1.0%) 1 (0.3%) 4 (0.6%) 7 (1.1%) 8 (1.3%) 15 (1.2%) LACERATION 3 (1.0%) 6 (2.0%) 9 (1.5%) 7 (1.1%) 8 (1.3%) 15 (1.2%)

HYPERCHOLESTEROLAEMIA 3 (1.0%) 7 (2.3%) 10 (1.6%) 10

(1.6%) 5 (0.8%) 15 (1.2%) DYSPNOEA 2 (0.6%) 3 (1.0%) 5 (0.8%) 6 (1.0%) 9 (1.4%) 15 (1.2%) VOMITING 2 (0.6%) 3 (1.0%) 5 (0.8%) 9 (1.4%) 5 (0.8%) 14 (1.1%) FATIGUE 1 (0.3%) 6 (2.0%) 7 (1.1%) 8 (1.3%) 6 (1.0%) 14 (1.1%)

CHEST PAIN 2 (0.6%) 3 (1.0%) 5 (0.8%) 10

(1.6%) 4 (0.6%) 14 (1.1%) OROPHARYNGEAL PAIN 3 (1.0%) 1 (0.3%) 4 (0.6%) 6 (1.0%) 8 (1.3%) 14 (1.1%) RASH 0 1 (0.3%) 1 (0.2%) 5 (0.8%) 9 (1.4%) 14 (1.1%) ARTHRITIS 3 (1.0%) 2 (0.7%) 5 (0.8%) 8 (1.3%) 5 (0.8%) 13 (1.0%)

MUSCULOSKELETAL PAIN 3 (1.0%) 2 (0.7%) 5 (0.8%) 10

(1.6%) 3 (0.5%) 13 (1.0%) SYNCOPE 4 (1.3%) 1 (0.3%) 5 (0.8%) 9 (1.4%) 4 (0.6%) 13 (1.0%) INSOMNIA 2 (0.6%) 2 (0.7%) 4 (0.6%) 6 (1.0%) 7 (1.1%) 13 (1.0%) BENIGN PROSTATIC HYPERPLASIA 3 (1.0%) 1 (0.3%) 4 (0.6%) 7 (1.1%) 6 (1.0%) 13 (1.0%) CYSTITIS 5 (1.6%) 6 (2.0%) 11 (1.8%) 5 (0.8%) 7 (1.1%) 12 (1.0%) RIB FRACTURE 0 3 (1.0%) 3 (0.5%) 5 (0.8%) 7 (1.1%) 12 (1.0%) SQUAMOUS CELL CARCINOMA 4 (1.3%) 4 (1.3%) 8 (1.3%) 9 (1.4%) 3 (0.5%) 12 (1.0%) TOOTH ABSCESS 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 9 (1.4%) 11 (0.9%) HERPES ZOSTER 3 (1.0%) 3 (1.0%) 6 (1.0%) 5 (0.8%) 6 (1.0%) 11 (0.9%) HYPOTENSION 1 (0.3%) 1 (0.3%) 2 (0.3%) 5 (0.8%) 6 (1.0%) 11 (0.9%) DIVERTICULITIS 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 4 (0.6%) 10 (0.8%) TOOTH INFECTION 1 (0.3%) 2 (0.7%) 3 (0.5%) 6 (1.0%) 4 (0.6%) 10 (0.8%) VERTIGO 2 (0.6%) 7 (2.3%) 9 (1.5%) 8 (1.3%) 2 (0.3%) 10 (0.8%) GASTROENTERITIS VIRAL 1 (0.3%) 0 1 (0.2%) 8 (1.3%) 2 (0.3%) 10 (0.8%) SKIN ABRASION 0 3 (1.0%) 3 (0.5%) 8 (1.3%) 2 (0.3%) 10 (0.8%) TRANSIENT ISCHAEMIC ATTACK 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 3 (0.5%) 9 (0.7%) ARRHYTHMIA 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 2 (0.3%) 8 (0.6%) GOUT 0 1 (0.3%) 1 (0.2%) 7 (1.1%) 1 (0.2%) 8 (0.6%) BURSITIS 1 (0.3%) 1 (0.3%) 2 (0.3%) 7 (1.1%) 1 (0.2%) 8 (0.6%) CORONARY ARTERY DISEASE 3 (1.0%) 4 (1.3%) 7 (1.1%) 3 (0.5%) 5 (0.8%) 8 (0.6%) OEDEMA PERIPHERAL 2 (0.6%) 5 (1.6%) 7 (1.1%) 3 (0.5%) 5 (0.8%) 8 (0.6%) DEHYDRATION 4 (1.3%) 1 (0.3%) 5 (0.8%) 7 (1.1%) 1 (0.2%) 8 (0.6%) LOWER RESPIRATORY TRACT INFECTION 2 (0.6%) 1 (0.3%) 3 (0.5% 6 (1.0%) 2 (0.3%) 8 (0.6%) GASTROENTERITIS 3 (1.0%) 2 (0.7%) 5 (0.8%) 4 (0.6%) 4 (0.6%) 8 (0.6%) CELLULITIS 3 (1.0%) 4 (1.3%) 7 (1.1%) 5 (0.8%) 3 (0.5%) 8 (0.6%) TOOTH EXTRACTION 0 1 (0.3%) 1 (0.2%) 7 (1.1%) 1 (0.2%) 8 (0.6%)





(n=312) q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

BLOOD PRESSURE INCREASED 3 (1.0%) 1 (0.3%) 4 (0.6%) 5 (0.8%) 3 (0.5%) 8 (0.6%) HYPOTHYROIDISM 3 (1.0%) 4 (1.3%) 7 (1.1%) 4 (0.6%) 3 (0.5%) 7 (0.6%) PROCEDURAL PAIN 3 (1.0%) 4 (1.3%) 7 (1.1%) 4 (0.6%) 3 (0.5%) 7 (0.6%) BASAL CELL CARCINOMA 11 (3.5%) 10 (3.3%) 21 (3.4%) 6 (1.0%) 1 (0.2%) 7 (0.6%) RESPIRATORY TRACT INFECTION 2 (0.6%) 1 (0.3%) 3 (0.5% 6 (1.0%) 1 (0.2%) 7 (0.6%) ASTHENIA 1 (0.3%) 2 (0.7%) 3 (0.5%) 6 (1.0%) 1 (0.2%) 7 (0.6%) SPINAL COLUMN STENOSIS 3 (1.0%) 1 (0.3%) 4 (0.6%) 3 (0.5%) 4 (0.6%) 7 (0.6%) ACUTE KIDNEY INJURY 1 (0.3%) 3 (1.0%) 4 (0.6%) 3 (0.5%) 4 (0.6%) 7 (0.6%) ECZEMA 5 (1.6%) 1 (0.3%) 6 (1.0%) 6 (1.0%) 1 (0.2%) 7 (0.6%) ABDOMINAL PAIN 4 (1.3%) 4 (1.3%) 8 (1.3%) 4 (0.6%) 2 (0.3%) 6 (0.5%) ASTHMA 3 (1.0%) 3 (1.0%) 6 (1.0%) 4 (0.6%) 2 (0.3%) 6 (0.5%) RHINORRHOEA 2 (0.6%) 3 (1.0%) 5 (0.8%) 3 (0.5%) 2 (0.3%) 5 (0.4%) LOWER RESPIRATORY TRACT CONGESTION 4 (1.3%) 1 (0.3%) 5 (0.8%) 0 4 (0.6%) 4 (0.3%) VITAMIN B12 DEFICIENCY 3 (1.0%) 0 3 (0.5%) 0 4 (0.6%) 4 (0.3%) OSTEOPOROSIS 3 (1.0%) 2 (0.7%) 5 (0.8%) 2 (0.3%) 2 (0.3%) 4 (0.3%) MUSCLE STRAIN 3 (1.0%) 5 (1.6%) 8 (1.3%) 1 (0.2%) 2 (0.3%) 3 (0.2%) BRADYCARDIA 1 (0.3%) 3 (1.0%) 4 (0.6%) 1 (0.2%) 2 (0.3%) 3 (0.2%) ABDOMINAL PAIN UPPER 2 (0.6%) 3 (1.0%) 5 (0.8%) 2 (0.3%) 1 (0.2%) 3 (0.2%) HAEMORRHOIDS 3 (1.0%) 1 (0.3%) 4 (0.6%) 2 (0.3%) 1 (0.2%) 3 (0.2%) SEBORRHOEIC KERATOSIS 3 (1.0%) 0 3 (0.5%) 1 (0.2%) 2 (0.3%) 3 (0.2%) ROTATOR CUFF SYNDROME 0 3 (1.0%) 3 (0.5%) 2 (0.3%) 1 (0.2%) 3 (0.2%) DYSPHAGIA 0 3 (1.0%) 3 (0.5%) 1 (0.2%) 1 (0.2%) 2 (0.2%) EPISTAXIS 5 (1.6%) 0 5 (0.8%) 1 (0.2%) 1 (0.2%) 2 (0.2%) BRONCHOSPASM 3 (1.0%) 1 (0.3%) 4 (0.6%) 0 2 (0.3%) 2 (0.2%) INTERVERTEBRAL DISC PROTRUSION 0 3 (1.0%) 3 (0.5%) 1 (0.2%) 1 (0.2%) 2 (0.2%) DEEP VEIN THROMBOSIS 1 (0.3%) 3 (1.0%) 4 (0.6%) 0 2 (0.3%) 2 (0.2%) RESTLESS LEGS SYNDROME 3 (1.0%) 0 3 (0.5%) 1 (0.2%) 1 (0.2%) 2 (0.2%) PROSTATOMEGALY 5 (1.6%) 3 (1.0%) 8 (1.3%) 1 (0.2%) 0 1 (<0.1%) MALIGNANT MELANOMA 3 (1.0%) 1 (0.3%) 4 (0.6%) 1 (0.2%) 0 1 (<1.0%) BREAST CANCER 0 3 (1.0%) 3 (0.5%) 1 (0.2%) 0 1 (<1.0%) CHRONIC KIDNEY DISEASE 1 (0.3%) 3 (1.0%) 4 (0.6%) 1 (0.2%) 0 1 (<1.0%) Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on N in the column headings. For frequency counts by preferred term, multiple occurrences of the same AE in an individual are counted only once. Table includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study in ≥1% of patients in any treatment group. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 13. Serious Ocular Adverse Events in the Study Eye, First 48 Weeks, Chroma and Spectri Pooled

Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total number of patients with at least 1 ocular SAE 12 (3.8%) 5 (1.6%) 17 (2.7%)

39 (6.2%)

38 (6.1%) 77 (6.2%)

Overall total number of SAEs 12 6 18 64 58 122 EYE DISORDERS

Total number of patients with at least 1 applicable AE 9 (2.9%) 5 (1.6%) 14 (2.3%)

17 (2.7%)

22 (3.5%) 39 (3.1%)

Total number of applicable AEs 9 6 15 25 23 48 VISUAL ACUITY REDUCED 5 (1.6%) 3 (1.0%) 8 (1.3%) 7 (1.1%) 8 (1.3%) 15 (1.2%) BLINDNESS TRANSIENT 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%) VISUAL ACUITY REDUCED TRANSIENTLY 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%) CHOROIDAL NEOVASCULARIZATION 1 (0.3%) 1 (0.3%) 2 (0.3%) 0 2 (0.3%) 2 (0.2%) NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 1 (0.2%) 3 (0.2%) BORDERLINE GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) CATARACT 0 0 0 0 1 (0.2%) 1 (<0.1%) IRITIS 0 0 0 0 1 (0.2%) 1 (<0.1%) OPEN ANGLE GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) OPTIC ISCHAEMIC NEUROPATHY 0 0 0 0 1 (0.2%) 1 (<0.1%) POSTERIOR CAPSULE OPACIFICATION 1 (0.3%) 0 1 (0.2%) 0 0 0 RETINAL ARTERY OCCLUSION 0 0 0 0 1 (0.2%) 1 (<0.1%) RETINAL DETACHMENT 0 1 (0.3%) 1 (0.2%) 0 0 0 RETINAL TEAR 0 0 0 0 1 (0.2%) 1 (<0.1%) ULCERATIVE KERATITIS 1 (0.3%) 0 1 (0.2%) 0 0 0 UVEITIC GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) VITREOUS FLOATERS 0 0 0 0 1 (0.2%) 1 (<0.1%) VITREOUS HAEMORRHAGE 0 0 0 0 1 (0.2%) 1 (<0.1%) VITRITIS 0 0 0 0 1 (0.2%) 1 (<0.1%)

INFECTIONS AND INFESTATIONS

Total number of patients with at least 1 applicable AE 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%) Total number of applicable AEs 0 0 0 3 2 5 ENDOPTHALMITIS 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

Total number of patients with at least 1 applicable AE 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 2 (0.3%) 4 (0.3%) Total number of applicable AEs 1 0 1 2 2 4 CORNEAL ABRASION 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 2 (0.3%) 4 (0.3%)

INVESTIGATIONS Total number of patients with at least 1 applicable AE 1 (0.3%) 0 1 (0.2%)

20 (3.2%)

16 (2.6%) 36 (2.9%)




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total number of applicable AEs 1 0 1 34 31 65 INTRAOCULAR PRESSURE INCREASED 1 (0.3%) 0 1 (0.2%)

20 (3.2%)

16 (2.6%) 36 (2.9%)

NERVOUS SYSTEM DISORDERS

Total number of patients with at least 1 applicable AE 1 (0.3%) 0 1 (0.2%) 0 0 0 Total number of applicable AEs 1 0 1 0 0 0 IIIRD NERVE PARALYSIS 1 (0.3%) 0 1 (0.2%) 0 0 0

Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on the N in the column headings. Table summary includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study. For frequency counts by preferred term, multiple occurrences of the same AE in an individual are counted only once. For frequency counts of "Total number of events" rows, multiple occurrences of the same AE in an individual are counted separately. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks; SAE, serious adverse event.



eTable 14. Non-Ocular Serious Adverse Events (SAEs) by MedDRA System Organ Class and Non-Ocular SAEs Occurring in ≥0.5% of Participants in any Treatment Group, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total number of patients with at least 1 non-ocular SAE

49 (15.7%)

54 (17.6%)

103 (16.6%)

120 (19.2%)

87 (13.9%) 207 (16.5%)

Overall total number of non-ocular SAEs 84 74 158 212 143 355 BLOOD AND LYMPHATIC SYSTEM DISORDERS 0 0 0 4 (0.6%) 1 (0.2%) 5 (0.4%)

ANAEMIA 0 0 0 3 (0.5%) 1 (0.2%) 4 (0.3%)

CARDIAC DISORDERS 8 (2.6%) 14 (4.6%) 22

(3.6%) 21 (3.4%) 25 (4.0%) 46 (3.7%) ATRIAL FIBRILLATION 3 (1.0%) 3 (1.0%) 6 (1.0%) 6 (1.0%) 5 (0.8%) 11 (0.9%) CARDIAC FAILURE CONGESTIVE 2 (0.6%) 1 (0.3%) 3 (0.5%) 5 (0.8%) 6 (1.0%) 11 (0.9%) ACUTE MYOCARDIAL INFARCTION 0 0 0 1 (0.2%) 4 (0.6%) 5 (0.4%) CORONARY ARTERY DISEASE 1 (0.3%) 4 (1.3%) 5 (0.8%) 0 0 0 CARDIAC ARREST 0 2 (0.7%) 2 (0.3%) 1 (0.2%) 0 1 (<0.1%)

EAR AND LABYRINTH DISORDERS 0 1 (0.3%) 1 (0.2%) 2 (0.3%) 0 2 (0.2%) GASTROINTESTINAL DISORDERS 5 (1.6%) 5 (1.6%)

10 (1.6%) 14 (2.2%) 12 (1.9%) 26 (2.1%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 2 (0.6%) 1 (0.3%) 3 (0.5%) 4 (0.6%) 1 (0.2%) 5 (0.4%) INFECTIONS AND INFESTATIONS

13 (4.2%) 6 (2.0%)

19 (3.1%) 18 (2.9%) 14 (2.2%) 32 (2.6%)

PNEUMONIA 7 (2.2%) 2 (0.7%) 9 (1.5%) 9 (1.4%) 5 (0.8%) 14 (1.1%) SEPSIS 2 (0.6%) 0 2 (0.3%) 1 (0.2%) 2 (0.3%) 3 (0.2%)

HEPATOBILIARY DISORDERS 1 (0.3%) 1 (0.3%) 2 (0.3%) 2 (0.3%) 1 (0.2%) 3 (0.2%) INJURY, POISONING AND PROCEDURAL COMPLICATIONS 8 (2.6%) 8 (2.6%)

16 (2.6%) 23 (3.7%) 25 (4%) 48 (3.8%)

FALL 3 (1.0%) 1 (0.3%) 4 (0.6%) 6 (1.0%) 4 (0.6%) 10 (0.8%) HIP FRACTURE 1 (0.3%) 1 (0.3%) 2 (0.3%) 4 (0.6%) 4 (0.6%) 8 (0.6%) FEMUR FRACTURE 0 0 0 4 (0.6%) 1 (0.2%) 5 (0.4%) ANKLE FRACTURE 2 (0.6%) 1 (0.3%) 3 (0.5%) 1 (0.2%) 0 1 (<0.1%) UPPER LIMB FRACTURE 0 0 0 1 (0.2%) 3 (0.5%) 4 (0.3%)

INVESTIGATIONS 1 (0.3%) 0 1 (0.2%) 4 (0.6%) 0 4 (0.3%) METABOLISM AND NUTRITION DISORDERS 3 (1.0%) 1 (0.3%) 4 (0.6%) 8 (1.3%) 2 (0.3%) 10 (0.8%)

DEHYDRATION 2 (0.6%) 0 2 (0.3%) 3 (0.5%) 0 3 (0.2%) MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 3 (1.0%) 5 (1.6%) 8 (1.3%) 10 (1.6%) 2 (0.3%) 12 (1.0%)

OSTEOARTHRITIS 1 (0.3%) 2 (0.7%) 3 (0.5%) 3 (0.5%) 0 3 (0.2%)




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) 8 (2.6%) 9 (2.9%)

17 (2.7%) 15 (2.4%) 14 (2.2%) 29 (2.3%)

BREAST CANCER 0 2 (0.7%) 2 (0.3%) 1 (0.2%) 0 1 (<0.1%) NERVOUS SYSTEM DISORDERS

10 (3.2%) 6 (2.0%)

16 (2.6%) 23 (3.7%) 11 (1.8%) 34 (2.7%)

SYNCOPE 3 (1.0%) 0 3 (0.5%) 5 (0.8%) 1 (0.2%) 6 (0.5%) CEREBROVASCULAR ACCIDENT 2 (0.6%) 1 (0.3%) 3 (0.5%) 4 (0.6%) 0 4 (0.3%) TRANSIENT ISCHAEMIC ATTACK 1 (0.3%) 0 1 (0.2%) 4 (0.6%) 1 (0.2%) 5 (0.4%)

PSYCHIATRIC DISORDERS 0 2 (0.7%) 2 (0.3%) 1 (0.2%) 0 1 (<0.1%) RENAL AND URINARY DISORDERS 2 (0.6%) 3 (1.0%) 5 (0.8%) 6 (1.0%) 6 (1.0%) 12 (1.0%)

NEPHROLITHIASIS 0 1 (0.3%) 1 (0.2%) 4 (0.6%) 0 4 (0.3%) REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.3%) 0 1 (0.2%) 0 3 (0.5%) 3 (0.2%) RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 1 (0.3%) 1 (0.3%) 2 (0.3%) 15 (2.4%) 10 (1.6%) 25 (2.0%)

CHRONIC OBSTRUCTIVE PULMONARY DISEASE 0 0 0 7 (1.1%) 3 (0.5%) 10 (0.8%) DYSPNOEA 0 1 (0.3%) 1 (0.2%) 1 (0.2%) 3 (0.5%) 4 (0.3%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS 1 (0.3%) 0 1 (0.2%) 1 (0.2%) 0 1 (<0.1%) SURGICAL AND MEDICAL PROCEDURES 0 0 0 1 (0.2%) 0 1 (<0.1%) VASCULAR DISORDERS 3 (1.0%) 1 (0.3%) 4 (0.6%) 5 (0.8%) 4 (0.6%) 9 (0.7%) Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on the N in the column headings. Table summary includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study. For frequency counts by preferred term, multiple occurrences of the same AE in an individual are counted only once. Table includes specific preferred terms for AEs that occurred in ≥0.5% of participants in any treatment group. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks; SAE, serious adverse event.



eTable 15. Adverse Events Leading to Death During the First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total No. (%) deaths 4 (1.3%) 3 (1.0%) 7 (1.1%) 7 (1.1%) 5 (0.8%) 12 (1.0%) CARDIAC DISORDERS

Total No. (%) of patients with applicable AE 2 (0.6%) 1 (0.3%) 3 (0.5%) 2 (0.3%) 0 2 (0.2%) CARDIAC ARREST 0 1 (0.3%) 1 (0.2%) 1 (0.2%) 0 1 (<0.1%) ACUTE MYOCARDIAL INFARCTION 0 0 0 1 (0.2%) 0 1 (<0.1%) MYOCARDIAL INFARCTION 1 (0.3%) 0 1 (0.2%) 0 0 0 VENTRICULAR FIBRILLATION 1 (0.3%) 0 1 (0.2%) 0 0 0

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 1 (0.2%) 0 1 (<0.1%) DEATH 1 (0.3%) 0 1 (0.2%) 1 (0.2%) 0 1 (<0.1%)


Total No. (%) of patients with applicable AE 0 1 (0.3%) 1 (0.2%) 1 (0.2%) 0 1 (<0.1%) PNEUMONIA 0 0 0 1 (0.2%) 0 1 (<0.1%) STAPHYLOCOCCAL SEPSIS 0 1 (0.3%) 1 (0.2%) 0 0 0


Total No. (%) of patients with applicable AE 0 1 (0.3%) 1 (0.2%) 1 (0.2%) 0 1 (<0.1%) BRAIN HERNIATION 0 0 0 1 (0.2%) 0 1 (<0.1%) INTERNAL INJURY 0 1 (0.3%) 1 (0.2%) 0 0 0

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 4 (0.6%) 6 (0.5%) GASTRIC CANCER 0 0 0 1 (0.2%) 0 1 (<0.1%) LUNG NEOPLASM MALIGNANT 0 0 0 0 1 (0.2%) 1 (<0.1%) MALIGNANT PLEURAL EFFUSION 0 0 0 0 1 (0.2%) 1 (<0.1%) METASTASES TO CENTRAL NERVOUS SYSTEM 0 0 0 0 1 (0.2%) 1 (<0.1%) OVARIAN CANCER METASTATIC 0 0 0 0 1 (0.2%) 1 (<0.1%) PROSTATE CANCER 0 0 0 1 (0.2%) 0 1 (<0.1%) PROSTATE CANCER METASTATIC 0 0 0 0 1 (0.2%) 1 (<0.1%) SMALL INTESTINE CARCINOMA METASTATIC 1 (0.3%) 0 1 (0.2%) 0 0 0




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)


Total No. (%) of patients with applicable AE 0 0 0 0 1 (0.2%) 1 (<0.1%) CEREBRAL HAEMORRHAGE 0 0 0 0 1 (0.2%) 1 (<0.1%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

Total No. (%) of patients with applicable AE 0 0 0 1 (0.2%) 0 1 (<0.1%) PNEUMONIA ASPIRATION 0 0 0 1 (0.2%) 0 1 (<0.1%)

Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on N in the column headings. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 16. Adverse Events Leading to Treatment Discontinuation, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Ocular, Study Eye Total No. (%) of patients with study eye AE leading to treatment discontinuation 4 (1.3%) 0 4 (0.6%) 7 (1.1%) 8 (1.3%) 15 (1.2%) Overall total number of applicable AEs 4 0 4 7 9 16 EYE DISORDERS

Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 3 (0.5%) 5 (0.8%) 8 (0.6%) Overall total number of applicable AEs 1 0 1 3 6 9 VITRITIS 0 0 0 1 (0.2%) 1 (0.2%) 2 (0.2%) CHOROIDAL NEOVASCULARIZATION 0 0 0 0 1 (0.2%) 1 (<0.1%) IRIDOCYCLITIS 0 0 0 0 1 (0.2%) 1 (<0.1%) IRITIS 0 0 0 0 1 (0.2%) 1 (<0.1%) OPTIC ISCHAEMIC NEUROPATHY 0 0 0 0 1 (0.2%) 1 (<0.1%) RETINAL ARTERY OCCLUSION 0 0 0 0 1 (0.2%) 1 (<0.1%) ULCERATIVE KERATITIS 1 (0.3%) 0 1 (0.2%) 0 0 0 UVEITIC GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) VISUAL ACUITY REDUCED 0 0 0 1 (0.2%) 0 1 (<0.1%)


Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 3 (0.5%) 2 (0.3%) 5 (0.4%) Overall total number of applicable AEs 1 0 1 3 2 5 ENDOPHTHALMITIS 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%) OPHTHALMIC HERPES ZOSTER 1 (0.3%) 0 1 (0.2%) 0 0 0


Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 0 0 0 Overall total number of applicable AEs 1 0 1 0 0 0 CORNEAL ABRASION 1 (0.3%) 0 1 (0.2%) 0 0 0

INVESTIGATIONS Total No. (%) of patients with applicable AE 0 0 0 1 (0.2%) 1 (0.2%) 2 (0.2%) Overall total number of applicable AEs 0 0 0 1 1 2 INTRAOCULAR PRESSURE INCREASED 0 0 0 1 (0.2%) 1 (0.2%) 2 (0.2%)





q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 0 0 0 Overall total number of applicable AEs 1 0 1 0 0 0 IIIRD NERVE PARALYSIS 1 (0.3%) 0 1 (0.2%) 0 0 0

Ocular, Fellow Eye Total No. (%) of patients with fellow eye AE leading to treatment discontinuation 0 0 0 0 1 (0.2%) 1 (<0.1%) Overall total number of applicable AEs 0 0 0 0 1 1 EYE DISORDERS

Total No. (%) of patients with applicable AE 0 0 0 0 1 (0.2%) 1 (<0.1%) Overall total number of applicable AEs 0 0 0 0 1 1 OPTIC ISCHAEMIC NEUROPATHY 0 0 0 0 1 (0.2%) 1 (<0.1%)

Non-Ocular Total No. (%) of patients with non-ocular AE leading to treatment discontinuation 9 (2.9%) 3 (1.0%)

12 (1.9%) 10 (1.6%) 10 (1.6%) 20 (1.6%)

Overall total number of applicable AEs 9 3 12 12 13 25 GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

Total No. (%) of patients with applicable AE 0 0 0 1 (0.2%) 0 1 (<0.1%) Overall total number of applicable AEs 0 0 0 1 0 1 ASTHENIA 0 0 0 1 (0.2%) 0 1 (<0.1%)

HEPATOBILIARY DISORDERS Total No. (%) of patients with applicable AE 0 0 0 1 (0.2%) 0 1 (<0.1%) Overall total number of applicable AEs 0 0 0 1 0 1 HEPATIC FAILURE 0 0 0 1 (0.2%) 0 1 (<0.1%)


Total No. (%) of patients with applicable AE 0 0 0 0 2 (0.3%) 2 (0.2%) Overall total number of applicable AEs 0 0 0 0 5 5 FALL 0 0 0 0 1 (0.2%) 1 (<0.1%) HIP FRACTURE 0 0 0 0 1 (0.2%) 1 (<0.1%) LOWER LIMB FRACTURE 0 0 0 0 1 (0.2%) 1 (<0.1%) ROAD TRAFFIC ACCIDENT 0 0 0 0 1 (0.2%) 1 (<0.1%) UPPER LIMB FRACTURE 0 0 0 0 1 (0.2%) 1 (<0.1%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

AND POLYPS) Total No. (%) of patients with applicable AE 6 (1.9%) 2 (0.7%) 8 (1.3%) 6 (1.0%) 6 (1.0%) 12 (1.0%) Overall total number of applicable AEs 6 2 8 6 6 12 PLASMA CELL MYELOMA 1 (0.3%) 1 (0.3%) 2 (0.3%) 0 0 0 B-CELL LYMPHOMA 0 0 0 0 1 (0.2%) 1 (<0.1%) BASAL CELL CARCINOMA 1 (0.3%) 0 1 (0.2%) 0 0 0 BREAST CANCER 0 0 0 1 (0.2%) 0 1 (<0.1%) INVASIVE DUCTAL BREAST CARCINOMA 1 (0.3%) 0 1 (0.2%) 0 0 0 LUNG ADENOCARCINOMA 0 0 0 0 1 (0.2%) 1 (<0.1%) LUNG NEOPLASM MALIGNANT 0 0 0 0 1 (0.2%) 1 (<0.1%) MALIGNANT MELANOMA STAGE IV 1 (0.3%) 0 1 (0.2%) 0 0 0 METASTASES TO CENTRAL NERVOUS SYSTEM 0 0 0 0 1 (0.2%) 1 (<0.1%) MYELODYSPLASTIC SYNDROME 0 0 0 0 1 (0.2%) 1 (<0.1%) MYXOFIBROSARCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) NEOPLASM MALIGNANT 0 0 0 0 1 (0.2%) 1 (<0.1%) NEUROENDOCRINE CARCINOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) NON−SMALL CELL LUNG CANCER METASTATIC 0 1 (0.3%) 1 (0.2%) 0 0 0 OESOPHAGEAL CANCER METASTATIC 0 0 0 1 (0.2%) 0 1 (<0.1%) OVARIAN CANCER 1 (0.3%) 0 1 (0.2%) 0 0 0 PANCREATIC CARCINOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) PROSTATE CANCER 1 (0.3%) 0 1 (0.2%) 0 0 0 WALDENSTROM’S MACROGLOBULINAEMIA 0 0 0 1 (0.2%) 0 1 (<0.1%)


Total No. (%) of patients with applicable AE 2 (0.6%) 1 (0.3%) 3 (0.5%) 3 (0.5%) 2 (0.3%) 5 (0.4%) Overall total number of applicable AEs 2 1 3 4 2 6 DEMENTIA 1 (0.3%) 1 (0.3%) 2 (0.3%) 0 1 (0.2%) 1 (<0.1%) AMYOTROPHIC LATERAL SCLEROSIS 0 0 0 1 (0.2%) 0 1 (<0.1%) CEREBROVASCULAR ACCIDENT 1 (0.3%) 0 1 (0.2%) 0 0 0 DEMENTIA ALZHEIMER'S TYPE 0 0 0 0 1 (0.2%) 1 (<0.1%) DIZZINESS 0 0 0 1 (0.2%) 0 1 (<0.1%) MEMORY IMPAIRMENT 0 0 0 1 (0.2%) 0 1 (<0.1%) TREMOR 0 0 0 1 (0.2%) 0 1 (<0.1%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

Total No. (%) of patients with applicable AE 1 (0.3%) 0 1 (0.2%) 0 0 0




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Overall total number of applicable AEs 1 0 1 0 0 0 SKIN NECROSIS 1 (0.3%) 0 1 (0.2%) 0 0 0

Investigator text for AEs coded using MedDRA version 20.0. Percentages are based on N in the column headings. For frequency counts by preferred term, multiple occurrences of the same AE in an individual are counted only once. For frequency counts of "Total number of events" rows, multiple occurrences of the same AE in an individual are counted separately. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks.



eTable 17. Ocular and Non-Ocular Adverse Events of Special Interest, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Ocular, Study Eye Total No. (%) of patients with study eye AE of special interest 9 (2.9%) 5 (1.6%)

14 (2.3%) 38 (6.1%)

31 (5.0%) 69 (5.5%)

Overall total number of applicable AEs 9 6 15 63 49 112 Suspected transmission of an infectious agent by the study drug 0 0 0 0 0 0 AE from medication error 0 0 0 0 0 0 Sight-threatening AEs (All)

Total No. (%) of patients with applicable AE 9 (2.9%) 5 (1.6%)

14 (2.3%) 38 (6.1%)

31 (5.0%) 69 (5.5%)

Overall total number of applicable AEs 9 6 15 63 49 112

Causes a decrease of ≥30 letters in VA score lasting more than 1 hour

Total No. (%) of patients with applicable AE 7 (2.2%) 3 (1.0%)

10 (1.6%) 8 (1.3%)

13 (2.1%) 21 (1.7%)

Overall total number of applicable AEs 7 4 11 9 13 22 VISUAL ACUITY REDUCED 5 (1.6%) 3 (1.0%) 8 (1.3%) 6 (1.0%) 7 (1.1%) 13 (1.0%) CORNEAL ABRASION 0 0 0 2 (0.3%) 2 (0.3%) 4 (0.3%) CHOROIDAL NEOVASCULARISATION 0 0 0 0 1 (0.2%) 1 (<0.1%) OPTIC ISCHAEMIC NEUROPATHY 0 0 0 0 1 (0.2%) 1 (<0.1%) POSTERIOR CAPSULE OPACIFICATION 1 (0.3%) 0 1 (0.2%) 0 0 0 RETINAL ARTERY OCCLUSION 0 0 0 0 1 (0.2%) 1 (<0.1%) ULCERATIVE KERATITIS 1 (0.3%) 0 1 (0.2%) 0 0 0 VITREOUS FLOATERS 0 0 0 0 1 (0.2%) 1 (<0.1%)

Requires surgical intervention to prevent permanent loss of sight

Total No. (%) of patients with applicable AE 0 0 0 10 (1.6%) 6 (1.0%) 16 (1.3%) Overall total number of applicable AEs 0 0 0 16 11 27 INTRAOCULAR PRESSURE INCREASED 0 0 0 7 (1.1%) 4 (0.6%) 11 (0.9%) VISUAL ACUITY REDUCED TRANSIENTLY 0 0 0 3 (0.5%) 1 (0.2%) 4 (0.3%) BLINDNESS TRANSIENT 0 0 0 1 (0.2%) 1 (0.2%) 2 (0.2%) RETINAL TEAR 0 0 0 0 1 (0.2%) 1 (<0.1%)

Associated with severe intraocular inflammation

Total No. (%) of patients with applicable AE 0 0 0 4 (0.6%) 2 (0.3%) 6 (0.5%) Overall total number of applicable AEs 0 0 0 4 2 6




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

ENDOPHTHALMITIS 0 0 0 3 (0.5%) 2 (0.3%) 5 (0.4%) UVEITIC GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%)

In the opinion of the investigator, it may require medical intervention to prevent permanent loss of sight

Total No. (%) of patients with applicable AE 2 (0.6%) 2 (0.7%) 4 (0.6%) 20 (3.2%)

14 (2.2%) 34 (2.7%)

Overall total number of applicable AEs 2 2 4 34 23 57 INTRAOCULAR PRESSURE INCREASED 0 0 0 13 (2.1%)

11 (1.8%) 24 (1.9%)

NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 1 (0.3%) 0 1 (0.2%) 2 (0.3%) 1 (0.2%) 3 (0.2%) BLINDNESS TRANSIENT 0 0 0 3 (0.5%) 0 3 (0.2%) CHOROIDAL NEOVASCULARISATION 1 (0.3%) 1 (0.3%) 2 (0.3%) 0 1 (0.2%) 1 (<0.1%) BORDERLINE GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) OPEN ANGLE GLAUCOMA 0 0 0 1 (0.2%) 0 1 (<0.1%) RETINAL DETACHMENT 0 1 (0.3%) 1 (0.2%) 0 0 0 VISUAL ACUITY REDUCED 0 0 0 1 (0.2%) 0 1 (<0.1%) VISUAL ACUITY REDUCED TRANSIENTLY 0 0 0 0 1 (0.2%) 1 (<0.1%)

Ocular, Fellow Eye Total No. (%) of patients with fellow eye AE of special interest 5 (1.6%) 2 (0.7%) 7 (1.1%) 10 (1.6%)

11 (1.8%) 21 (1.7%)

Overall total number of applicable AEs 6 2 8 10 11 21 Suspected transmission of an infectious agent by the study drug 0 0 0 0 0 0 AE from medication error 0 0 0 0 0 0 Sight-threatening AEs (All)


11 (1.8%) 21 (1.7%)

Overall total number of applicable AEs 6 2 8 10 11 21

Causes a decrease of ≥30 letters in VA score lasting more than 1 hour


10 (1.6%) 19 (1.5%)

Overall total number of applicable AEs 5 2 7 9 10 19 VISUAL ACUITY REDUCED 4 (1.3%) 2 (0.7%) 6 (1.0%) 7 (1.1%) 7 (1.1%) 14 (1.1%) DRY AGE-RELATED MACULAR DEGENERATION 0 0 0 2 (0.3%) 1 (0.2%) 3 (0.2%) FOREIGN BODY IN EYE 0 0 0 0 1 (0.2%) 1 (<0.1%) NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 0 0 0 0 1 (0.2%) 1 (<0.1%)

Requires surgical intervention to prevent permanent loss of sight

Total No. (%) of patients with 1 (0.3%) 0 1 (0.2%) 0 0 0




q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

applicable AE Overall total number of applicable AEs 1 0 1 0 0 0 GLAUCOMA 1 (0.3%) 0 1 (0.2%) 0 0 0

Associated with severe intraocular inflammation 0 0 0 0 0 0 In the opinion of the investigator, it may require medical intervention to prevent permanent loss of sight

Total No. (%) of patients with applicable AE 0 0 0 1 (0.2%) 1 (0.2%) 2 (0.2%) Overall total number of applicable AEs 0 0 0 1 1 2 CHOROIDAL NEOVASCULARIZATION 0 0 0 1 (0.2%) 0 1 (<0.1%) NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 0 0 0 0 1 (0.2%) 1 (<0.1%)

Non-Ocular Total No. (%) of patients with applicable AE 0 0 0 0 0 0 Overall total number of applicable AEs 0 0 0 0 0 0 Elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice 0 0 0 0 0 0 Suspected transmission of an infectious agent by the study drug 0 0 0 0 0 0 AE from medication error 0 0 0 0 0 0 Investigator text for AEs is coded using MedDRA version 20.0. Sight-threatening AEs (All) include the following categories: decrease ≥30 letters, surgical intervention, severe inflammation, may require medical intervention. Per the protocol, all sight-threatening AEs of special interest are considered serious adverse events. Table summary includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks; VA, visual acuity.



eTable 18. Increased Intraocular Pressure in the Study Eye and Fellow Eye, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg

q4w

(n=312) q6w

(n=307) Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Study Eye Any post-baseline pre-dose incidence of IOP ≥30 mm Hg

1/311 (0.3%)

0/307 (0%) 1/618 (0.2%) 5/623(0.8%)

3/625 (0.5%) 8/1248 (0.6%)

Any post-baseline post-dose incidence of IOP ≥30 mm Hg

1/311 (0.3%)

1/307 (0.3%) 2/618 (0.3%)

52/625 (8.3%)

35/626 (5.6%)

87/1251 (7.0%)

With ≥2 times post-baseline post-dose incidence of IOP ≥30 mm Hg a 0/307 (0%)

0/305 (0%) 0/612 (0%)

23/616 (3.7%)

12/614 (2%)

35/1230 (2.8%)

Incidence of AE of IOP increased 4 (1.3%) 6 (2.0%) 10 (1.6%) 83 (13.3%)

58 (9.3%) 141 (11.3%)

Incidence of SAE of IOP increased 1 (0.3%) 0 1 (0.2%) 20 (3.2%)

16 (2.6%) 36 (2.9%)

Total No. (%) of patients with same-day post-injection IOP AE 3 (1.0%) 6 (2.0%) 9 (1.5%) 95 (15.2%)

67 (10.7%) 162 (12.9%)

INTRAOCULAR PRESSURE INCREASED 3 (1.0%) 5 (1.6%) 8 (1.3%) 81 (12.9%)

58 (9.3%) 139 (11.1%)

VISUAL ACUITY REDUCED TRANSIENTLY 0 1 (0.3%) 1 (0.2%) 9 (1.4%) 9 (1.4%) 18 (1.4%) BLINDNESS TRANSIENT 0 0 0 8 (1.3%) 7 (1.1%) 15 (1.2%) SUDDEN VISION LOSS 0 0 0 0 0 0

No. patients receiving treatment for same-day post-injection IOP AE

None 0 4 4 27 17 44 Medication 3 1 4 52 38 90 Procedure 0 1 1 20 19 39

Total No. of same-day post-injection IOP AEs 3 6 9 170 123 293

Event rate per 1000 injections 0.8 2.3 1.4 23.4 23.7 23.5 INTRAOCULAR PRESSURE INCREASED 3 (0.8) 5 (1.9) 8 (1.3) 142 (19.6)

105 (20.3) 247 (19.8)

BLINDNESS TRANSIENT 0 0 0 19 (2.6) 7 (1.4) 26 (2.1) VISUAL ACUITY REDUCED TRANSIENTLY 0 1 (0.4) 1 (0.2) 9 (1.2) 11 (2.1) 20 (1.6) SUDDEN VISION LOSS 0 0 0 0 0 0

No. treatments for same-day post-injection IOP AE



None 0 4 4 59 37 96 Medication 3 1 4 77 55 132 Procedure 0 1 1 36 34 70

Fellow Eye Any post-baseline incidence of IOP ≥30 mm Hg 0/311 (0%)

1/307 (0.3%) 1/618 (0.2%) 3/623 (0.5%)

2/624 (0.3%) 5/1247 (0.4%)

Baseline is the last available value taken on or before the day of randomization. Unscheduled post-baseline IOP measurements were included as pre-dose IOP. Patients with multiple incidents are counted once. Abbreviations: AE, adverse event; IOP, intraocular pressure; q4w, every 4 weeks; q6w, every 6 weeks; SAE, serious adverse event. a Denominator included patients with at least 2 post-baseline post-dose IOP.



eTable 19. Neovascular Age-Related Macular Degeneration in the Study and Fellow Eyes, First 48 Weeks, Chroma and Spectri Pooled Sham Lampalizumab 10 mg MedDRA System Organ Class: MedDRA Preferred Term

q4w (n=312)

q6w (n=307)

Pooled (n=619)

q4w (n=626)

q6w (n=626)

Pooled (N=1252)

Study Eye Total No. (%) of patients with applicable AE 5 (1.6%) 2 (0.7%) 7 (1.1%)

12 (1.9%)

12 (1.9%) 24 (1.9%)

NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 3 (1.0%) 1 (0.3%) 4 (0.6%) 6 (1.0%) 9 (1.4%) 15 (1.2%) CHOROIDAL NEOVASCULARISATION 2 (0.6%) 1 (0.3%) 3 (0.5%) 6 (1.0%) 3 (0.5%) 9 (0.7%) RETINAL NEOVASCULARISATION 0 0 0 0 0 0 Fellow Eye Total No. (%) of patients with applicable AE 3 (1.0%) 5 (1.6%) 8 (1.3%)

10 (1.6%)

11 (1.8%) 21 (1.7%)

NEOVASCULAR AGE-RELATED MACULAR DEGENERATION 1 (0.3%) 1 (0.3%) 2 (0.3%) 4 (0.6%) 7 (1.1%) 11 (0.9%) CHOROIDAL NEOVASCULARISATION 2 (0.6%) 4 (1.3%) 6 (1.0%) 6 (1.0%) 4 (0.6%) 10 (0.8%) RETINAL NEOVASCULARISATION 0 0 0 0 0 0 Investigator text for AEs is coded using MedDRA version 20.0. Table summary includes AEs that started or worsened (for existing condition) on or after the date of first study treatment and occurred during the first 48 weeks of the study. Ocular AEs with missing eye attribution are tabulated in both study eye and fellow eye summaries. Abbreviations: AE, adverse event; MedDRA, Medical Dictionary for Regulatory Activities; q4w, every 4 weeks; q6w, every 6 weeks.



eFigure 1. Adjusted Mean Geographic Atrophy Area Change From Baseline to Week 48: (A) Chroma: overall; (B) Spectri: overall; (C) Chroma: CFI+; (D) Spectri CFI+; (E) Chroma CFI−; (F) Spectri CFI−.

Mixed effect model repeated measures analysis, overall and by biomarker group, adjusted for baseline GA area, subfoveal vs non-subfoveal location, and multifocal vs non-multifocal configuration; baseline best-corrected visual acuity category; and sex. The overall analysis included an additional covariate adjustment for biomarker group. Error bars are 95% CIs. Abbreviations: CFI, complement factor I; GA, geographic atrophy; q4w, every 4 weeks; q6w, every 6 weeks.



eFigure 2. Adjusted Mean Change in Geographic Atrophy (GA) Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Chroma and Spectri Pooled



A, Lampalizumab every 4 weeks (q4w) vs sham; B, lampalizumab every 6 weeks (q6w) vs sham. Sample sizes shown are the number of participants with data at week 48. The mean change from baseline was estimated from a mixed effects model repeated-measures analysis adjusted for baseline GA area, subfoveal vs nonsubfoveal location, and multifocal vs nonmultifocal configuration; complement factor I–profile biomarker status; baseline best-corrected visual acuity (BCVA) category; and sex; excluding baseline covariates not relevant for the particular subgroup. The pooled analysis included an additional covariate adjustment for study. Difference = lampalizumab minus sham pooled. Low-luminance deficit (LLD) = BCVA minus low-luminance visual acuity. DA indicates the number of disc areas



eFigure 3. Adjusted Mean Change in GA Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Lampalizumab q4w Versus Sham: (A) Chroma; (B) Spectri

The sample sizes shown in the table are the number of patients with data at week 48. Mean change from baseline was estimated from a mixed effect model repeated measures analysis adjusted for baseline GA area, subfoveal vs non-subfoveal location, and multifocal vs non-multifocal configuration; complement factor I (CFI)-profile biomarker status; baseline BCVA category; and sex; excluding baseline covariates not relevant for the particular subgroup. Difference = lampalizumab minus sham pooled. Low-luminance deficit (LLD) = BCVA minus low-luminance visual acuity (LLVA). Abbreviations: BCVA, best-corrected visual acuity; DA, disc areas; GA, geographic atrophy; q4w, every 4 weeks.



eFigure 4. Adjusted Mean Change in GA Area From Baseline to Week 48 in the Study Eye by Clinical Subgroup, Lampalizumab q6w Versus Sham: (A) Chroma; (B) Spectri

The sample sizes shown in the table are the number of patients with data at week 48. Mean change from baseline was estimated from a mixed effect model repeated measures analysis adjusted for baseline GA area, subfoveal vs non-subfoveal location, and multifocal vs non-multifocal configuration; complement factor I (CFI)-profile biomarker status; baseline BCVA category; and sex; excluding baseline covariates not relevant for the particular subgroup. Difference = lampalizumab minus sham pooled. Low-luminance deficit (LLD) = BCVA minus low-luminance visual acuity (LLVA). Abbreviations: BCVA, best-corrected visual acuity; DA, disc areas; GA, geographic atrophy; q6w, every 6 weeks.



eFigure 5. Mean Change in Best-Corrected Visual Acuity Over Time From Baseline to Week 48: (A) Chroma and Spectri pooled; (B) Chroma; (C) Spectri

Mixed effect model repeated measures analysis adjusted for baseline BCVA, baseline geographic atrophy lesion location, biomarker status, and sex. The pooled analysis included an additional covariate adjustment for study. Abbreviations: BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; q4w, every 4 weeks; q6w, every 6 weeks.

0 12 24 48

-10

-8

-6

-4

-2

0

2

Study Week

Sham Pooled

Lampalizumab q4w

Lampalizumab q6w

36

0 12 24 48

-10

-8

-6

-4

-2

0

2

Study Week

Sham Pooled

Lampalizumab q4w

Lampalizumab q6w

36

0 12 24 48

-10

-8

-6

-4

-2

0

2

Study Week

Sham Pooled

Lampalizumab q4w

Lampalizumab q6w

36



eFigure 6. Mean (A) Pre-Dose and (B) Post-Dose Intraocular Pressure (IOP) in mm Hg Over Time in the Study Eye, First 48 Weeks, Chroma and Spectri Pooled

A.

B.

Error bars indicate 95% CIs. Abbreviations: q4w, every 4 weeks; q6w, every 6 weeks.


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