Development of Human Gene Therapy Protocols at the University of Florida
Pre-clinical and Phase I Clinical Protocol Development
Phase I trials are primarily done to determine safety, that is, insure that the dose used in clinical applications is not toxic or have side effects that would preclude the therapy’s use in human patients. If correctly designed, a Phase I trial can also yield information about how effective the therapy will be.
The typical US regulatory plan is to initially request an informal meeting (pre-preIND) with pharmacology and toxicology reviewers in the FDA Office of Cellular, Tissue, and Gene Therapies to discuss the toxicology and biodistribution plans for animal studies. These proposed studies can be modified prior to their initiation based on comments received from FDA.
A preclinical study protocol will be issued according to the Quality Assurance Unit (QAU) procedure for the toxicology and biodistribution studies. The study director will be responsible for executing the preclinical studies according to the study protocol and in compliance with GLP regulations. QAU will select random phases of the study protocol for audit or inspection to ensure compliance with the protocol and written standard operating procedures (SOPs). QAU will audit the raw data/observations and the final report(s) to ensure the final report accurately reflects the raw data. The testing laboratory has established written procedures for operation, cleaning and maintenance of equipment involved in the preclinical studies. Critical equipment has been calibrated by approved vendors and is recalibrated according to an established schedule. Methods that will be utilized to process, analyze and evaluate samples collected during the preclinical studies will be executed according to written procedures. Personnel responsible for these methods will be properly trained and this training will be documented. Data generated by these methods will be recorded, analyzed and reported according to written procedures. QAU oversight of these activities will ensure accurate and reliable preclinical toxicology and biodistribution study data as well as assurance that the reports will be acceptable to regulatory authorities.
Once data from GLP studies is obtained, a formal pre-IND meeting will be requested from FDA. A pre-IND information package will be submitted that will include data from the preclinical studies, the proposed clinical protocol, and vector manufacturing and testing information. FDA will then be able to provide the investigator with informed suggestions that can be used to prepare for IND submission. In addition to the IND, a submission will be prepared and submitted to the NIH Office of Biotechnology Activities (NIH/OBA) for review by the Recombinant DNA Advisory Committee (RAC). The submission will consist of the proposed clinical protocol and consent and responses to a number of questions provided in Appendix M of the NIH Guidelines for Research Involving Recombinant DNA Molecules, among other items. Any comments received from the RAC can then be incorporated into the protocol and consent submitted as part of the IND. Once all governing agencies are agreed upon the safety of the study, the investigator may begin enrolling human subjects.
More details and clinical trial information coming soon. Please go to clinicaltrials.gov for specifics on gene therapy trials currently enrolling participants.