The National Institutes of Health has launched an adaptive phase 3 clinical trial to evaluate the safety and efficacy of three immune modulator drugs to help with cytokine storm in hospitalised adults with COVID-19.
Cytokine storm is an immune reaction that is seen in some COVID-19 patients where their immune system unleashes excessive amounts of proteins that trigger inflammation that can lead to acute respiratory distress syndrome, multiple organ failure and other life-threatening complications.
The trial, known as ACTIV-1 Immune Modulators (IM), aims to determine if modulating the immune reaction that leads to cytokine storm can reduce the need for ventilators and shorten hospital stays. The study will evaluate if the therapeutics are able to restore balance to an overactive immune system.
The ACTIV-1 IM trial is a part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative. The National Institute of Health (NIH) announced the ACTIV initiative in April 2020 to develop a national research response to prioritise and speed the development of the most promising COVID-19 treatments and vaccines.
The ACTIV-1 IM expects to enrol approximately 2,100 hospitalised adults with moderate to severe COVID-19 at medical facilities in the United States and Latin America.
“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, MD, PhD. “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,” he added.
Adaptive master protocols 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, said the researchers.
The team selected three IM agents for the study including infliximab (Remicade, Janssen); abatacept (Orencia, Bristol Myers Squibb) and cenicriviroc (Cvc, AbbVie).
All participants in the trial will receive remdesivir, as the current standard of care treatment of hospitalised patients with COVID-19. 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 utilisation. The enrollment is now open, and the trial is expected to last approximately six months.