Muscular Dystrophy and Other Clinical Trials Adapting to Life With COVID-19

In a Facebook Live event hosted by the Muscular Dystrophy Association (MDA), experts discussed the effect that the COVID-19 pandemic has had on research efforts in muscular dystrophy, as well as the ongoing development of a potential COVID-19 vaccine.

Clinical trials are a critical part of understanding human disease and testing potential therapies. In particular, some current trials may pave the way for substantial improvements in treating muscular dystrophy and similar disorders.

“I think for many of our inherited diseases of nerve and muscle, we’re at this sort of transitional point where we’re really talking the actual possibility of potentially transformational therapies in the next few years,” Jeffrey Statland, MD, said at the MDA event. “So we’re very committed to trying to get these studies to move forward.”

Statland, a professor of neurology at the University of Kansas Medical Center, is involved in several research efforts related to muscular dystrophy, including as co-principal investigator on ReSolve (NCT03458832). This observational natural history study aims to speed potential treatments for facioscapulohumeral muscular dystrophy (FSHD) by developing tools — new outcome measures and biomarkers — for use in future trials.

“Neuromuscular clinical trials are still taking place, but as you can imagine, COVID has affected our ability to do the neuromuscular clinical trials in many of the same ways that it’s impacted our lives,” Statland said.

Specifically, the pandemic has limited personal contact and interaction, and put an emphasis on avoiding all but essential travel. Studies, however, traditionally rely on patient visits to hospitals or clinics for testing that evaluates a candidate therapy or approach.

Investigators need to adapt trial protocols to overcome such obstacles.

Statland described as an example the process of making changes to ReSolve, a study involving 220 people across the U.S. and a number in Europe, once it became clear that COVID-19 would be an ongoing crisis.

“We got all of our site [investigators] on a phone call, we discussed it with the National Institutes of Health, who was sponsoring us and our study statistician. We made the decision to collect questionnaires that people can do from home, to do them just like we would normally do.

“We decided to expand our visit windows, because we thought the most important thing was keeping people in our study. So, for example, a 12-month visit could occur anywhere from nine months to 15 months.”

Other adaptations made to ReSolve include a “pilot project to get remote assessments,” like two-way video evaluations of how quickly a person could walk or get up from a chair and turn, and by using small devices that capture motion.

“Our thought was to do this to prepare for a future” where clinical trials might “suddenly need to … substitute a home visit for one that would’ve been done in person,” he said.

Ensuring the safety of everyone taking part in trials and the collection of “quality data” were key concerns in ReSolve’s move away from in-person visits and toward assessments that can be performed remotely.

Statland sees this move as something of a “silver lining” to the way the pandemic has disrupted clinical trials.

“They say adversity breeds innovation, and I think that’s really been true here as well,” he said. “I’m quite optimistic about this move toward remote assessments, and this idea of decentralized clinical trials. We’ve really been discussing it for almost a decade.”

Such changes, he added, “would be a major benefit in rare diseases,” where the ability to go to a study center multiple times during a trial is often a limitation.

“So, [if] we could decentralize this, allow people to join from home, I think more people could potentially be able to participate in studies, in the trial process,” he added.

The necessary tools allowing for such changes while protecting the integrity of trial data still need to be validated — that is, shown to be reliable and consistent, he added.

ReSolve is currently enrolling FSHD patients in the U.S.; information on study locations can be found here.

Statland stressed that safety policies related to the pandemic vary from place-to-place, and anyone interested in participating in a clinical study should check those in effect at their preferred or selected site.

The race for a COVID-19 vaccine

While the ongoing pandemic has hindered clinical trials in various ways, it also opened opportunities for research that aims to combat the disease. A major focus of ongoing biomedical research is into vaccines that can protect against COVID-19.

Almost 200 potential vaccines are under development worldwide. One furthest along is BNT162b2, by BioNTech and Pfizer, which is being tested in a large Phase 2b/3 clinical trial in the U.S. and elsewhere (NCT04368728). This placebo-controlled trial reportedly will enroll “up to 44,000” healthy adults; details on locations and contacts can be found here.

Vaccine development can often take a decade or more, so the speed with which potential COVID-19 vaccines such as BNT162b2 have advanced is unprecedented.

BNT162b2 is a messenger RNA (mRNA) vaccine, which is part of what has allowed the vaccine to be so quickly developed. Most vaccines require all or part of the virus itself, meaning that the virus needs to be grown in large quantities to produce the vaccine.

In contrast, mRNA vaccines work by delivering a portion of the virus’s genetic code to a person’s cells. Then, those cells make the viral protein, which is recognized by the immune system to induce anti-viral immunity.

Practically, this means that an mRNA vaccine can be made without actually producing the virus — all that is required is knowing the genetic code.

“After researchers in China published the code for the new coronavirus in early January … Our collaborators at BioNTech, a German company, were able to start work on [the vaccine] without having to obtain and grow the virus,” said David L. Swerdlow, MD, COVID vaccine global medical team leader at Pfizer, and an infectious disease-trained physician and epidemiologist.

“So, it’s safer, quicker, and faster to make an mRNA vaccine than other types of vaccines,” he added.

In addition to the vaccine’s biology, substantial logistical steps have been necessary to bring vaccines to development with such speed.

“We’ve been doing things simultaneously, instead of one step at a time,” Swerdlow said.

As an example, Pfizer in a Phase 1 clinical trial (NCT04380701) evaluated four different vaccine candidates at once — of these, BNT162b2 was determined to be the most promising, for both efficacy and safety, and was chosen to move ahead.

Notably, Pfizer will also work with the U.S. Food and Drug Administration to assess whether more tests are necessary to determine if people on immunosuppressants could safely be given this vaccine, Swerdlow said.

He added that companies are already gearing up to manufacture and distribute their vaccines, even before receiving regulatory approval.

“Companies are willing to take the chance that, if the vaccine is successful [in trials], they will be able to start delivering the vaccine almost immediately. If the vaccine is not successful, they will have lost a good deal of money, but given the circumstances, it is worth the risk,” Swerdlow said.

He recommended that people be sure get the flu shot this year, helping to “prevent as many cases of the flu as possible.”

More information on Pfizer’s vaccine clinical trial, including information on participating, can be found at www.covidvaccinestudy.com.