The National Institutes of Health (NIH) along with their National Institutes of Child Health and Human Development (NICHD) and the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental health are sponsoring the IMPAACT 2032 study, focusing on the effects of remdesivir (Gilead) in pregnant women who have been prescribed the drug to treat COVID-19. Conducted at 17 trial site locations in both the United States and Puerto Rico, the study sponsors seek to better understand how pregnant women metabolize the drug and whether there are any potential side effects. The trail site and investigational network conducting the study is funded by the NIH—the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network. Interestingly, although the World Health Organization (WHO) Solidarity study has concluded remdesivir shows no benefit and some studies raise health considerations, federal dollars continue to get allocated to investigate this drug. In the USA and around much of the world, remdesivir is heavily used for patients hospitalized with COVID-19. Physicians currently lack evidence for the safety and efficacy of remdesivir for treating pregnant women with COVID-19. As pregnancy may influence the drug’s effects, this study compares the use of the drug in pregnant women and non-pregnant women of reproductive age who happened to be hospitalized with the coronavirus.
The Study Drug
Originally developed to treat Ebola and Marburg virus infections, remdesivir was shown in a NIAID-funded clinical trial to accelerate recovery in patients with advanced COVID-19 disease. Remdesivir has since been approved by the U.S. Food and Drug Administration for the treatment of COVID-19 in adults and children over age 12 years. Gilead received considerable support early on by NIAID and the ACTT-1 clinical trials, first leading to emergency use authorization (EUA) then formal FDA approval. The company has since generated nearly $3 billion in revenue in the first several months of sales.
Based on the results of the Solidarity trial, the WHO recommends against the use of remdesivir. Prominent intensive care doctors in Europe also feel remdesivir should not be used under any circumstances. The Solidarity trial involved over 7,000 patients hospitalized with COVID-19. Gilead had countered these findings, challenging the quality of the WHO-based study. TrialSite can attest that on a number of cases in hospital settings the drug appears to reduce duration of disease by at least a few days. The NIAID-based study concluded that the drug cut down hospitalization from 15 days down to 11 days. TrialSite reported in January that the University of Cincinnati study did lead investigators toward some safety concerns. Led by Bingfang Yan, researchers suggest using caution when using the drug moving forward. The study suggests that remdesivir may be used too extensively in the hospital setting involving COVID-19 patients. Why? The UC-led study uncovered that remdesivir stops activity associated with CES-2, an enzyme required for breakdown of a number of medications in the intestine, liver and kidney.
The FDA label for remdesivir (VEKLURY) confirms that the drug can lead to more levels of liver enzymes that could represent problems.
Why study on pregnant women?
Although it has not been approved specifically for use in pregnancy, remdesivir can be prescribed to pregnant women if their physicians believe the drug may benefit them. However, physicians currently lack scientific evidence for the safety and efficacy of remdesivir for treating pregnant women with COVID-19. Because pregnancy may influence a drug’s effects, IMPAACT 2032 will compare remdesivir use in pregnant and non-pregnant women of reproductive age who are hospitalized with COVID-19.
The study will evaluate remdesivir’s pharmacokinetics—how a drug is absorbed, moves through the body and is broken down and eliminated in pregnant women and nonpregnant women of childbearing potential who receive it as part of clinical care. For women who received the drug within five days of delivery, samples from the plasma and umbilical cord will be analyzed for insight into remdesivir’s pharmacokinetics in the placenta. Breast milk will also be tested for remdesivir among women who are lactating. Researchers will also document potential side effects and adverse events that could occur with use of the drug.
“Pregnant women with COVID-19 are at high risk for hospitalization, for intensive care admission and for needing ventilator support,” said Diana W. Bianchi, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “There is an urgent need to identify effective treatments for this population and to determine whether drugs prescribed for other adults are appropriate for use in pregnancy.”
This Phase 1 clinical trial (NCT04582266) focuses on an investigation into the pharmacokinetic (PK) properties and safety of remdesivir administered to pregnant and non-pregnant women with COVID-19. The Phase 1 prospective, open label, non-randomized opportunistic PK study in pregnant and non-pregnant women of childbearing potential hospitalized and received Remdesivir treatment of COVID-19.
Who is leading this Study?
Mark Mirochnick, MD, Study Chair, Department of Pediatrics, Boston University
Diana Clarke, PharmD, Study Chair, Pediatric Infectious Diseases, Boston Medical
Brookie Best, Pharm D, MAS, Study Chair, University of California, San Diego
Call to Action: TrialSite will monitor this Phase 1 safety-related study focusing on pregnant women taking remdesivir. Sign up for the daily newsletter for more updates.