In Advarra’s inaugural virtual symposium, panelists will shared tips on overcoming obstacles to optimize study startup and the impact of manufacturing challenges on a study startup. Representing industry and academic perspectives, these experts brought their unique gene therapy research experience to the conversation, exploring the challenges this field of research poses for research sites, sponsors, CROs, and study participants.

Following the presentation, panelists addressed questions submitted by the audience in a Q&A session. Due to time constraints we weren’t able to answer all questions live, so our experts have responded to some of the most popular topics in this 2-part blog. Click here to read part 1.

Q: Is there a standard or up-to-date resource for the safety practices for gene therapy conducting clinical trial sites?
A: There are general government guidelines (e.g., NIH Guidelines), but the best resource is utilizing an institutional biosafety committee (IBC) focused on review of gene therapy studies. The IBC can provide guidance based on the specific study and the site where the research takes place.

Q: Would a typical Phase I study with a single ascending dose (SAD) and multiple ascending dose (MAD) be considered for mRNA therapies?
A: Yes, this type of design is currently in use for some mRNA therapies. Because of the transient nature of mRNA, you can use traditional study design approaches such as a SAD/MAD study.

Q: Is there a currently approved mRNA vaccine?
A: There are no approved mRNA vaccines at this time.

Q: Is there a place for small molecule therapies in the age of gene therapy?
A: Yes, there are many gene therapies administered in conjunction with small molecules and monoclonal antibodies.

Q: How do you ensure you safely conduct study-related procedures in a patient care environment (for both staff and patients/participants)?
A: Undergo IBC review to ensure the risks are identified and adequately addressed.

Q: How can we predict a participant’s susceptibility to adverse symptoms in gene therapy and management?
A: This is part of the IBC’s risk assessment process and also why the IBC reviews the informed consent form (ICF). The IBC looks at the nature of the genetically modified investigational product, as well as the method of delivery and the participant population, and can then utilize that risk assessment to anticipate likely adverse events.

Ultimately this depends on the product being investigated and the targeted participant population. Prior to conducting clinical trials, the sponsor must conduct appropriate nonclinical trials to assess potential risk to humans. The inclusion/exclusion criteria should be written in a way to exclude individuals at greatest risk and ensure those most likely to benefit are included. If a gene therapy is only effective against a specific mutation, then participants should undergo genetic testing to ensure they have the mutation—otherwise they would only bear risk without the possibility for benefit.

Q: Can gene therapy be used for early disease diagnosis? Does genetic screening factor into gene therapy?
A: You wouldn’t use gene therapy for early disease diagnosis, but you might use genetic screening to identify people who are likely to develop a disease that could be treated or prevented through gene therapy. If you have people with a mutation who can be treated with gene therapy, the genetic screening would be an important component of the inclusion criteria.

Q: How should researchers create study standard operating procedures (SOPs) for the IBC when they are not the experts on the investigational product (and the sponsor doesn’t provide such SOPs)?
A: The IBC may be able to provide guidance (and possibly study-specific template SOPs) based on its review of the protocol, investigator’s brochure, and pharmacy manual (if available). Research sites can also contact the study sponsor for help and guidance—you might be surprised by the tools and resources sponsors can provide. Research staff should also consider communicating with internal departments and teams who have more experience in this space.

Q: How can we overcome public fears of genetic research to enable recruitment?
A: Success in early trials that shows a dramatic impact in improving patient outcomes and quality of life will help a lot. For example, in the symposium we discussed the little boy with mutations to the RPE65 gene, a condition that previously had no treatment—it was simply expected that patients would go blind by adolescence. This is thankfully no longer the case thanks to gene therapy research.

Education is also important here. Explaining to participants how the gene therapy will work and what risks are associated with it takes away a lot of frightening “unknowns.” Also, people may not know that many commonplace therapeutics are actually gene therapy products. Recognizing these “un-scary” gene therapy products are already part of regular medical practice can help make the “scarier” products seem less so.

Want to get the basics on gene therapy research and its rapid expansion in the clinical setting? Watch our webinar Preparing for Multisite Gene Therapy Studies.

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