NIH begins large clinical trial to test immune modulators
for treatment of COVID-19
The National Institutes of Health (NIH) has launched an adaptive Phase 3 clinical trial to evaluate the safety and efficacy of three immune modulator drugs in hospitalized adults with COVID-19. Some COVID-19 patients experience an immune response in which the immune system unleashes excessive amounts of proteins that trigger inflammation — called a “cytokine storm” — that can lead to acute respiratory distress syndrome, multiple organ failure and other life-threatening complications. The clinical trial aims to determine if modulating that immune response can reduce the need for ventilators and shorten hospital stays. Part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, the trial, known as ACTIV-1 Immune Modulators (ACTIV-1 IM), will determine if the therapeutics are able to restore balance to an overactive immune system.
Abatacept, cenicriviroc and infliximab
ACTIV-1 IM is a randomized, placebo-controlled trial that uses an adaptive master protocol. One of the hallmarks of master protocols is that they allow coordinated and efficient evaluation of multiple investigational agents as they become available. This enables maximum flexibility to swiftly weed out drugs that do not demonstrate effectiveness, identify those that do in a short time frame, and rapidly incorporate additional experimental agents into the trial. The ACTIV public-private partnership selected three agents for the study from a pool of over 130 immune modulators initially reviewed based on several factors, including their relevance to COVID-19, strong evidence for use against inflammatory reaction and cytokine storm, and availability for large-scale clinical studies. The initial agents are infliximab (Remicade® – J&J; abatacept (Orencia®), developed by BMS; and cenicriviroc (CVC), an investigational late-stage agent developed by AbbVie. “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. “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.”
Up to 2,160 patients to be enrolled in the US and in Latin America
All participants in the trial will receive remdesivir, convalescent plasma and dexamethasone will be allowed at the discretion of the site investigator and in accordance with national guidelines. They will be randomly assigned to receive a placebo or one of the immune modulators as an add-on treatment. The trial will study the different combination treatment regimens with respect to illness severity, recovery speed, mortality and hospital resource utilization. The trial expects to enroll approximately 2,160 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). Enrollment is now open, and the trial is expected to last approximately six months. Results will be available shortly after the trial is completed, or possibly sooner if analysis conducted during the trial indicates that one or more of the drugs is beneficial. To ensure that the trial is being conducted in a safe and effective manner, an independent data and safety monitoring board will oversee the trial and conduct periodic reviews of the accumulating data.