Paula M. Jacobs, Ph.D. SAIC Frederick Cancer Imaging Program/DCTD/NCI/NIH September 5, 2006 Phase 0...
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Transcript of Paula M. Jacobs, Ph.D. SAIC Frederick Cancer Imaging Program/DCTD/NCI/NIH September 5, 2006 Phase 0...
Paula M. Jacobs, Ph.D.SAIC Frederick
Cancer Imaging Program/DCTD/NCI/NIH September 5, 2006
Phase 0 Trials in Oncologic Drug Development
DCTD Phase 0 WorkshopDCTD Phase 0 Workshop
Nuts and Bolts:You Too Can Prepare an
IND
Overview of Early Development
Synthesize a number of new imaging drugs
Evaluate them in pre-clinical settings Pick the best ones to test in humans Learn to prepare them consistently Perform in vivo pharmacology and
toxicology in appropriate animal models Chose initial dose for human studies:
least risk Assemble the data and submit to FDA or
to your RDRC Obtain IRB approval Test in human subjects
Approach to Regulatory Requirements
Regulations are the same for Labeled therapeutic agents Functional imaging agents General imaging agents
Development strategy may differ with goal Basic information about a therapeutic Basic information about a tumor Imaging for evaluating response to
therapy
Investigational Clinical Trials
The sponsor must apply for permission to study drugs in humans From FDA for IND – traditional or
exploratory From the Radioactive Drugs Research
Committee (RDRC) at your institution From an IRB for either
“Sponsor” Individual physician Institution Industry
RDRC vs. IND
RDRC: for basic research only E.g., kinetics, distribution, dosimetry NOT safety or efficacy Pediatric studies restricted Only small doses and few patients Drug must have been in humans before
IND: not restricted to basic research Can study safety and efficacy (i.e., clinical trials) Can do basic research Pediatric studies less restricted
Types of IND
Three types of traditional INDs: An investigator initiated IND Emergency use IND (E-IND) Treatment IND
And a new type: Exploratory (“phase 0”, x-IND)
What’s the difference?
Traditional Single agent Plans for Phase 1, 2, 3 trials and NDA Extensive pre-clinical data needed to begin Dose escalation, therapeutic evaluation
Exploratory Multiple agents under one IND, go/no go Microdose, first in man studies No therapeutic intent Biodistribution, pharmacokinetics, safety Less pre-clinical data required Resubmit as Traditional IND if successful
FDA Guidance on the IND process with multiple links to other documentation: http://www.fda.gov/cder/regulatory/applicatio
ns/ind_page_1.htm
Comprehensive FDA Guidance Page http://www.fda.gov/cder/guidance/
guidance.htm
An “how-to” guide from the Biological Development Program at NCI-Frederick with multiple links http://wwwbdp.ncifcrf.gov/pdf/GuidetoRegSub
s.pdf
Schedule a pre-IND meeting
Where to get information
Talk to th
e FDA!
Nuts and Bolts of an IND
What data are needed What supporting information
is needed How is the application put
together What happens when it is
submitted
Information Required in INDs
Pharmacology/toxicology in animals
Dosimetry for radiopharmaceuticals
CMC: Chemistry, Manufacturing and Controls
Some of these data may be referenced from existing INDs or the literature
Clinical Information
Clinical Protocols and Investigator Information
Detailed protocol for clinical study
Qualifications of clinical investigators
Commitments To obtain informed consent To obtain review of the study by an
institutional review board (IRB) To adhere to the investigational new
drug regulations
IND Application
1. Form 1571 (Application)
2. Table of Contents of Application
3. Introductory Statement
4. General Investigational Plan
5. Investigators’ Brochure (multi-site)
6. Protocol Study Protocol Investigator Data – Form 1572, CV
IND Application
7. Chemistry, Manufacturing, and Control Data
8. Pharmacology and Toxicology Data
9. Previous Human Experience
10. Additional Information. Dosimetry Letter from IND or DMF-holder allowing
cross- reference to their files Site/NCI Data and Safety Monitoring Plan Cited literature
Practical Issues
Make it easy for multiple reviewers to find and understand the information – repeat information in different sections
Include all sections, even if empty Comprehensive Table of Contents and
TOC for any section more than a few pages
Consecutive page numbers for entire IND (can be numbered by section )
Include copies of all cited literature Don’t assume the reviewers will be
expert in your subject area
What happens next?
Submit 5-15 copies (ask FDA Division)
Wait 30 calendar days before beginning the first study on IND
The document goes to several reviewers
FDA reviews the IND first and foremost for risk to subjects – NOT for scientific interest
FDA may request changes Safety related in protocol Purity/safety related in CMC
FDA will call/fax with questions
The Next Speaker is:
Dr. Anthony Shields