Eligibility for Gene Therapy Clinical Trials

FAQs > What Screenings May Be Required?

What Screenings May Be Required?

What screenings may be required for an investigational gene therapy clinical trial for hemophilia?

Multiple investigational gene therapy clinical trials for hemophilia are currently underway, and each one is different. Before beginning a clinical trial, potential participants are screened to determine who is eligible (inclusion criteria) or ineligible (exclusion criteria). Because clinical trials differ, they typically have different screenings. That means if you are not eligible for one clinical trial, you may still be eligible for another.

Common screenings for a hemophilia gene therapy clinical trial may include:

Age (eg, 18 years or older)

Severity of hemophilia

Factor inhibitor status

Overall health history, including health of the liver

Overall health history
(ie, health of the liver)

Pre-existing neutralizing
antibodies (NAbs)

These are just some of the screenings a gene therapy clinical trial for hemophilia may review. Every clinical trial is different, so you should talk to your doctor and healthcare team if you are considering participating in one to make sure you understand it.

To learn about the screening for a particular clinical trial, be sure to visit ClinicalTrials.gov.

What Screenings May Be Required?
NEXT LEVEL

Let’s take a closer look at some common screenings briefly described above.

Age

In general in both cases, adeno-associated virus (AAV) gene therapy clinical trials for hemophilia have only allowed adult enrollment. Often, clinical trials will start enrollment for an adult population before enrolling adolescents or children. An additional consideration in gene therapy research is that a younger person’s liver may still be growing. It is unknown if the effect of the new functional gene delivered through gene therapy could be reduced as the liver continues to grow.

Disease severity

In hemophilia, disease severity is classified by the amount of endogenous (naturally occurring) clotting factor activity in the body. To date, most clinical trials have restricted enrollment to only those people who have less than or equal to 1-2% clotting factor activity.

Factor inhibitors

The presence of inhibitors or having a history of inhibitor activity may exclude people from participating in a gene therapy trial for hemophilia, but every clinical trial is different. Talk to your doctor about which one may be right for you.

Overall health

Each clinical trial may have different enrollment criteria as they relate to other medical conditions, including HIV, active Hepatitis C infection, and overall health of the liver.

Neutralizing antibodies

A common screening specific to gene therapy clinical trials for hemophilia is for pre-existing neutralizing antibodies, commonly called NAbs. NAbs indicate prior exposure to the AAV used in gene therapy, and if present, you may not be eligible for the clinical trial.

Learn More About NAbs
ADVANCED

NAbs’ role in the eligibility criteria

AAVs occur naturally in the environment, so there is a chance that a person may have previously been exposed to a specific AAV and their immune system created anitbodies to fight it off. The immune system does a great job at protecting us from these outside “invaders” such as bacteria and viruses—and that’s a good thing! The challenge in gene therapy research is that viruses like AAVs, which are normally seen as "invaders" by the body's immune system, are being used as potential vectors (delivery vehicles).

Our bodies are clever and will “remember” this prior exposure by keeping those NAbs around to defend against that same virus again in the future.

In this scenario, the NAbs could recognize the AAV vector being used for gene therapy and destroy it before it’s able to deliver the new functional gene to the target cells. Scientists in the gene therapy research field are working hard to overcome this challenge.

Someone who has pre-existing NAbs for a specific AAV may not be eligible to participate in a gene therapy clinical trial that uses that specific AAV vector. Pre-existing NAbs and their effect on eligibility may be different from one trial to another because different types of AAV vectors are being used in different trials. To determine if NAbs may affect your eligibility, clinical trials commonly include an AAV-neutralizing antibody test as part of the screening process for enrollment.

You can learn more about the eligibility criteria for specific gene therapy clinical trials for hemophilia and the type of vector being used in each trial at ClinicalTrials.gov.

What should I evaluate in clinical trials