Planning a Gene Therapy Trial? Ask an Expert — and Pay Attention

It’s been 46 years since researchers Theodore Friedmann and Richard Roblin published a landmark paper in the journal Science that posed a provocative question: “Gene therapy for human genetic disease?” And while clinical trials for gene therapy drugs have become much more common in the past 20 years — more than 2,400 had been conducted through 2017 — the science is still a long way from mainstream.

So if you’re initiating or planning a gene therapy trial, here are two pieces of advice:

  1. Surround yourself with experts.
  2. Listen to what they have to say.

Whether those experts come from a CRO or a regulatory consultancy, their help will be critical in helping develop the trial, meet with the Institutional Biosafety Committee, establish a timeline, and manage expectations. Here’s why.

Timing is tight. The window for administering gene therapy treatments is often very small. Sensitive compounds need special handling, and if you pick an unreliable shipping vendor, your expensive product could be delayed on a tarmac and rendered useless. And if your drug is subject to review by the RAC — the federal government’s Recombinant DNA Advisory Committee — plan to submit all your materials eight weeks in advance of the committee’s next meeting. They’re held quarterly, so a misstep that causes you to miss the next session automatically costs you at least three months.

Patients are people, too. Patients in gene therapy trials are often in desperate situations, and these trials can be very burdensome — even terrifying — for patients and their families. Just the coaching and preparation involved in getting them to sign up can consume a lot of time and energy.

Attaining informed consent. You need to enlist regulatory experts and patient engagement pros to develop the proper informed consent, and possibly informed assent, language — an especially big challenge when working with children. In particular, the hazard communication in the consent template must be written so that it’s clear to patients and family members.

Finding patients and sites. Gene therapy trials typically target rare diseases, some so rare that it’s very difficult to find patients. That might mean taking the trial to where the patents are, no matter how far-flung a place that might be. It might require a long search for a site that meets Western standards for infrastructure and staffing. And you may need to get familiar with the language, laws, and ethical standards of unfamiliar countries.

Going to the globe’s remote corners can raise a host of other challenges. Patients may need a medical visa. Young patients and siblings relocating for the duration of the trial need to enroll in school. Family members may have trouble seeking work in-country to support themselves. Even clearing the family pet for the temporary move can be an undertaking. A big help, we’ve found, is hiring a cultural mediator to help the family acclimate.

Supporting the sites

Once we’ve moved past the planning and are surrounded by a team of experts, we need to support the site and the staff in every way possible. The facilities involved in this research typically require multimillion-dollar infrastructure, including a clean room with controlled airflow, where every reagent and piece of material entering and leaving is highly regulated. The staff is also highly specialized, the technology is complex — and as is often the case in gene therapy trials (and rare disease research in general), the study team can be very large.

The requirements get more specific depending on the condition under study. Suppose, for example, you’re dealing with a type of genetic muscular dystrophy. You might want a geneticist on the team to help identify patients and ultimately provide genetic confirmation of the disease. Depending on the method of drug delivery, you might need a surgeon to help deliver genes to the body, along with resident MRI guidance.

Or say you’re working with neonates. Anything and everything we can do to minimize the amount of blood drawn from children is essential to the success of the trial, so you have to work with specialty labs. Kids’ blood is clumpy, so you need a lab runner on site to make sure samples are processed and put through the centrifuge within an hour to avoid losing any samples.

There are many other special circumstances and considerations when planning a gene therapy trial. Engaging experts up front can save a lot of misdirected effort and expense, and put your study on a productive path. For more information, check out our white paper on Operationalizing Gene Therapy Trials.