Participating in a Clinical Trial

The drug-approval process takes many years to evaluate the safety and efficacy of potential new therapies. There are many considerations to discuss with your doctor and family when interested in joining a clinical trial.

The safety and well-being of patients are top priorities.

After many years of initial (preclinical) research, which includes laboratory, manufacturing, and animal studies, investigational new therapies may then be reviewed and authorized by the FDA for research studies in humans, known as clinical trials. Clinical trials include multiple phases and extensive review of data to—first and foremost—ensure the safety of patients.

*In gene therapy, typically phases 1 and 2 are combined.

*If approved by appropriate regulatory agency, research and monitoring of product on market will continue.

Results from clinical trials provide insights into the safety, effectiveness, and appropriateness of the gene therapy being studied.

Potential risks of gene therapy

Gene therapy research offers an exciting potential for the development of new therapies. But, as with any new treatment being researched, there are challenges and risks. To help identify these challenges and risks, gene therapies are studied in clinical trials under controlled conditions for several years. To better understand what research has uncovered to date and how that’s shaping the prospective future of gene therapy research, review the potential risks that are being actively investigated. Below is not a comprehensive list of risks and challenges.

Click on each potential challenge and risk to learn more:

The job of the immune system is to defend against pathogens, such as viruses, germs, and other “invaders,” from outside the body that could cause harm or sickness when inside the body. The challenge is that we are trying to use what is normally seen as an “invader” (a virus) by the body as a potential treatment. For this reason, it is possible that the vector (a modified virus) could be recognized as an invader and trigger an immune response. While this defense mechanism is normal and expected, it could cause the immune system to resist, or attempt to fight off, the gene therapy. This is because the immune system may see the vector, acting as the delivery vehicle for gene therapy, as something that isn’t supposed to be there. This may lead to immune responses in the body, such as:

  • Swelling of the liver, which, if not controlled, could lead to a decrease or loss of the factor protein made from investigational gene therapy. Treatment, such as a short course of steroids, may be required to calm the immune system.
  • The development of antibodies in response to AAV gene therapy, which could make someone ineligible for AAV gene therapy research and potential future treatments. This is because the antibodies would recognize the previously identified AAV gene therapy and escort it out of the body.
  • The development of antibodies against FVIII or FIX (also called inhibitors), which would limit the ability of gene therapy to work as desired.
  • Allergic reactions ranging from mild to severe.

After gene therapy, individuals are able to return to their previous treatment should their doctor deem it necessary. It is not known yet if someone will be able to receive a second dose of gene therapy.

  • While vectors tend to be specific in the cells they target, there is still a risk that vectors could find their way into unintended cells. This could damage those cells or cause inappropriate cell growth, leading to tumors or cancer. There have not been any cases of tumors or cancer reported as a result of hemophilia gene therapy, but researchers and regulators are closely monitoring for this potential risk.
  • After the gene therapy is administered, it may be removed (or shed) from the body in fluids such as urine, semen, or saliva through a process known as vector shedding. While rare, this could lead to the transmission of vector particles which could potentially cause infection in people who come into contact with these fluids. For example, condom use for contraception may be required for 9-10 months postinfusion, or longer for some patients.

An immune response could affect the liver:

  • Swelling of the liver, which, if not controlled, could lead to liver damage or a decrease or loss of the factor protein made from the investigational gene therapy. If needed, one approach to manage the immune system is the use of drugs that temporarily suppress the immune response, called immunosuppressive or immunomodulatory drugs, such as steroids.
    • The liver is the target for hemophilia gene therapy. Liver health will be monitored during and after receiving gene therapy.

Learn more about what to expect after a gene therapy clinical trial.

This is not intended to be a comprehensive list of challenges and risks. Studies are ongoing, and participants continue to be followed to measure safety and effectiveness of AAV gene therapies. Additional risks may be identified in the future. Discuss the possible risks of gene therapy with your doctor.

Participating in any clinical trial is a big decision.



To prepare for conversations with your healthcare team, take a few minutes to prepare a personalized discussion guide.