Two COVID-19 Clinical Trials Seek to Enroll Pregnant Women

Bar and her colleagues officially launched the trials in May, running one for patients hospitalized with COVID-19 and one specifically for COVID-19 patients on ventilators. While no expecting mothers have enrolled to date, their pregnancy would not preclude them from the trials—a first for a clinical study of COVID-19 treatments. The Scientist spoke with Bar about her decision to include pregnant women in her studies and the potential challenges of doing so more commonly in clinical research. 

The Scientist: What led you to do this study, and what exactly are you doing?

Katharine Bar: We thought, especially early in the epidemic, that convalescent plasma was a promising treatment modality for people who are sick with COVID-19. So the concept of convalescent plasma—that you can take [plasma containing] antibodies from people who have recovered from an infection and . . . you can give them . . . to another person who was earlier in their stages of disease and hasn’t made their own antibodies, and this can be helpful for treatment. That is a process that has been used in multiple infections over time. We can give [convalescent plasma] to people in what we believe is a safe way, much more quickly than we can go through the regulatory and research and development process that it takes to either get monoclonal antibodies or other antibody preparations up and going. 

That was the impetus for the studies initially. And I think it still follows. As of right now, there’s been a lot of convalescent plasma being given in a compassionate use framework. The Mayo Clinic has an expanded access program that many hospitals have participated in, and they’ve actually released safety data on more than 20,000 individuals who received COVID-19 convalescent plasma, so we do have a good sense that it is safe. . . . But whether it’s effective and in which populations it’s effective is not yet known. That’s why we wanted to do at Penn a little bit more of a rigorous approach. 

We have two studies. The first study is in mechanically ventilated participants, so quite sick people. And this is a single arm study where we’re giving plasma to all of the [50] individuals. But we designed it in a way that would be parallel to other trials running around the same time so that we can, through an arrangement with these other trials, compare our participants with matched individuals with COVID-19 who were placebo recipients for other trials. . . . The second trial is our own randomized controlled trial. And so within Penn, we’re hoping to enroll up to 80 participants: half the people get plasma and a half of them don’t. And then we compare whether plasma plus standard of care versus standard of care alone [in terms of] safety and efficacy. 

TS: Why did you think it was important to enroll pregnant women?

Ultimately, pregnant women suffer from having fewer drugs available to them, because we don’t test them upfront in the process of clinical trials.

KB: In my previous day job, we do a lot of HIV clinical trials. And I think in HIV, like most other large diseases, we recognize that there’s a disconnect between the full population of individuals who are affected by the disease process and those who are enrolled in clinical trials. And that’s for good reasons and bad reasons. . . . If we’re not sure about the safety, we don’t want to take unnecessary risks. And certainly, we’re concerned about pregnant women—there could be problems that the pregnant woman would uniquely face or that the fetus would face, and so we oftentimes don’t include pregnant women in research because we’re trying to protect pregnant women and their fetuses. But the downside of that is that then when these drugs do become developed and are demonstrated to be safe and effective, we don’t have good understanding of if they are also safe and effective for pregnant women. So ultimately, pregnant women suffer from having fewer drugs available to them, because we don’t test them upfront in the process of clinical trials. So it’s a little bit of a catch 22. 

We have an extremely long track record of safety of giving, not COVID-19 convalescent plasma, but just plasma in general, to lots of different groups, including pregnant women. So we give plasma—fresh frozen plasma or antibody preparations from plasma—we give it to pregnant women all the time [for blood loss], and so we have a good sense of what the safety of plasma is in this population. . . . It’s perhaps easier for a product like convalescent plasma than it is for others [such as a new drug] and so we should take advantage of this and sort of get the ball rolling in this regard. . . . To my knowledge, it’s the first COVID-19 therapeutic trial at Penn that is including pregnant women. 

TS: Was the regulatory approval process more challenging because you included pregnant women in your protocols for these trials?

There was a very strong desire from everyone involved to get this therapy up and going as fast as possible. So for instance, our FDA [Food and Drug Administration] approval and our IRB [institutional review board] process was very fast. We got expedited reviews for everything—basically as soon as we sent the protocols in, the IRB convened and reviewed our protocol [and] met with us within a couple of days. . . It was an incredibly expedited process. Part of that is because everything else was shut down and so they were able to dedicate time and energy to getting this moving quickly . . . [and also] because plasma has been shown to be safe in many contexts, as well as with COVID-19. But for pregnant women, we had to go through the full IRB review process. So it wasn’t that extraordinary of a level of regulatory or logistics, but everything was so fast paced for the primary trial process, that sort of going back to normal levels of convening the full IRB, giving them the appropriate amount of time to review everything, meeting their stipulations, resubmitting, etc.—that took a little extra time. So it was a two- to three-week delay to get pregnant women included in each of the protocols after we[started enrolling in the general population]. 

TS: How far are you along in enrollment in each of the two trials? 

We have about 25 participants in each. 

TS: And do you have any pregnant women?

We do not, in fact. Since we opened both of these studies, basically the beginning of May for mechanically ventilated and the middle of May for our randomized control hospitalized patients, we haven’t had any pregnant women who met enrollment criteria. So there are lots of COVID-positive pregnant women coming through the Penn system. But fortunately, in the past . . . month and a half, we haven’t had any that were substantially symptomatic from COVID pneumonia. . . . So that’s great. And I think that reflects [the fact that] numbers in general in our region are going down. 

TS: Can you speak a little bit more about the inclusion of pregnant women in clinical trials more broadly, even after the pandemic?

It is a burden for these trials, for regulatory and safety [reasons], to include pregnant women. And of course, any adverse event in a pregnant woman or for a fetus would be a really serious and negative outcome. But ultimately we have to deal with that in order to get to the place we want to be, which is where we understand what is safe and what is unsafe for pregnant women so we can more effectively treat that population, which is always going . . . to need to be treated for the same things that everyone else deals within society.