FDA Releases Guidance on CGT Early-Stage Trials
Because cellular and gene therapy products can have more severe effects than other types of drug products, potentially leading to organ failure, tumors or death, sponsors should include these as primary safety objectives when designing early-phase clinical trials, the FDA says.
The trial should assess the nature and frequency of potential adverse events and how they relate to dose, the final guidance says. A year or more of follow-up is appropriate for each subject. For CGT products that remain active in the body indefinitely or where there is concern that cells might transform, migrate or cause ectopic tissue to develop, monitoring should continue for many years, the FDA says.
The agency says clinical trials on pediatric patients are possible, but sponsors need to consider how they will incorporate additional safeguards. If a company plans to conduct a pediatric trial when no prior safety or efficacy data in adults exists, it must explain why adult studies are unethical or infeasible, the FDA says. The agency notes, for example, a disease that has a swift downward course in children, but is milder and easily managed when it afflicts adults.
On dosing, the guidance points out that in cases where there is no previous human experience with a specific CGT product, treating subjects simultaneously could represent an unreasonable risk. Instead, treatments should be staggered to limit the number of subjects who might be exposed to such risk.
The FDA suggests using control groups when the natural history of the disease is not well-characterized or when the severity of the study participants’ disease may vary widely. For some CTG products, use of an intrasubject control — such as an injection of the investigation product into one limb and a control agent into another — may be useful in assessing localized effects, the agency says.
The guidance also offers recommendations pm cohort size, patient-specific products and operator training. And it includes tips on general preclinical program design, including animal species, model selection and proof-of-concept studies.
Sponsors are urged to communicate early and frequently with CBER’s Office of Cellular, Tissue and Gene Therapies due to the pace at which these products are evolving.
The guidance finalizes a draft version initially released in 2012. Read it at www.fdanews.com/06-15-CGTproducts.pdf. — John Bechtel