The National Institutes of Health (NIH) today announced the launch of a Phase III clinical trial to determine the safety and efficacy for patients hospitalized with COVID-19 of three separate immune modulator drugs. The clinical trial aims to determine if modulating an excessive immune response can reduce the need for ventilators and shorten hospital stays.
Clinicians have observed that in some patients with COVID-19, the immune system becomes dysregulated, unleashing excessive amounts of proteins that trigger inflammation. Called a “cytokine storm,” this immune reaction can lead to serious life-threatening complications, including multiple organ failure and acute respiratory distress syndrome. The trial is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, and the trial, called ACTIV-1 Immune Modulators (IM), will examine the ability of therapeutic interventions to restore balance in the immune system.
“This is the fifth master protocol to be launched under the ACTIV partnership in an unprecedented timeframe, and focuses efforts on therapies that hold the greatest promise for treating COVID-19,” said NIH Director Francis S. Collins, M.D., Ph.D., in a press release. “Immune modulators provide another treatment modality in the ACTIV therapeutic toolkit to help manage the complex, multi-system conditions that can be caused by this very serious disease.”
The three drugs to be studied are infliximab (Remicade), from Janssen Research & Development, from Johnson & Johnson’s Janssen Pharmaceutical; abatacept (Orencia), from Bristol Myers Squibb BMS); and Cenicriviroc (CVC), an investigational late-stage agent developed by AbbVie. The candidates were chosen from a pool of more than 130 immune modulators selected for relevance to COVID-19, strong evidence for use against inflammatory reaction and cytokine storm, and availability for large-scale clinical studies.
ACTIV-1 IM is a randomized, placebo-controlled trial that uses an adaptive master protocol, which allows for the coordinated and efficient evaluation of multiple investigational agents as they become available. This trial design allows for the quick evaluation of drug to quickly eliminate those are aren’t effective and to introduce new experimental agents over the course of the study.
The trial seeks to enroll approximately 2,100 hospitalized adults with moderate to severe COVID-19 at medical facilities in the United States and Latin America. The National Center for Advancing Translational Sciences (NCATS), part of NIH, will coordinate and oversee the trial with funding support from the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, in support of the Trump administration’s Operation Warp Speed.
In the study, all participants will receive the drug remdesivir, the current standard of care for patients hospitalized with COVID-19. Additional treatments, either convalescent plasma or dexamethasone if administered via current guidelines, and at the discretion of the site investigator. Patients will either receive one of the treatments, or placebo, and the three drug combinations will be evaluated for illness severity, recovery speed, mortality, and hospital resource utilization. The trial, which is currently enrolling patients, is expected to last six months. NCATS’ Clinical and Translational Science Awards (CTSA) Program and the Trial Innovation Network will play a key role in adding U.S. study sites and enrolling patients, including those from communities disproportionately affected by COVID-19.
“The CTSA Program’s nimbleness and innovation in conducting clinical trials—along with the network’s extensive capacity and broad geographical reach—have positioned it to rapidly implement this important trial,” said NCATS Director Christopher P. Austin, M.D. “The innovative trial design will allow efficient evaluation of three different potential COVID-19 treatments concurrently, delivering new possible treatments for patients more quickly and valuable insights into the science of clinical translation.”