NIH Launches Trial to Test Immune Modulator Drugs for COVID-19

NIH recently launched a Phase 3 clinical trial to evaluate the safety and efficacy of three immune modulator drugs in hospitalized COVID-19 patients. 

The trial, which is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, will enroll 2,100 hospitalized adults with moderate to severe COVID-19. It is called the ACTIV-1 Immune Modulators (IM) trial.

ACTIV selected three agents for the study from a pool of over 130 immune modulators. The three agents are Johnson & Johnson’s infliximab (REMICADE), Bristol Myers Squibb’s abatacept (ORENCIA), and Cenicriviroc (CVC), an investigational late-stage agent developed by AbbVie.

The agents were selected based on several factors, including their relevance to COVID-19, evidence for use against inflammatory reaction, and availability for large-scale clinical studies.

Overall, the trial will determine if therapeutics can restore balance to  overactive immune systems in COVID-19 patients and uncover different combination treatment regimens concerning illness severity, recovery speed, mortality, and hospital resource utilization, NIH said. 

“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,” Christopher P. Austin, MD, NCATS director said in a statement announcing the launch of the trial.

Some COVID-19 patients have experienced an immune response in which the immune system generates excessive amounts of proteins that trigger inflammation. This phenomenon known as cytokine storm can lead to acute respiratory distress syndrome, multiple organ failure, and other life-threatening complications for COVID-19 patients.

The clinical trial aims to determine where modulating the immune response can decrease the need for ventilators and shorten hospital stays, NIH explained in the statement.

While participating in the trial, patients will also receive remdesivir, the current standard of care treatment for COVID-19 patients. Additionally, convalescent plasma and dexamethasone will be allowed, following national guidelines, and patients will be randomly assigned to receive a placebo or one of the immune modulators as an add-on treatment. 

NCATS’ Clinical and Translational Science Awards (CTSA) Program and the Trial Innovation Network will play a key role in adding US study sites and enrolling patients.

The trial is expected to last approximately six months, with results available shortly after.

Notably, the trial uses an adaptive master protocol, which allows for coordinated and efficient evaluation of multiple investigational agents as they become available.

This enables flexibility to get rid of drugs that do not demonstrate effectiveness, identify those that do, and incorporate additional experimental agents into the trial, NIH explained.

“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 Francis S. Collins, MD, PhD, NIH director. “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.”

Back in April, NIH announced the ACTIV initiative, which aimed to develop a national research response to prioritize and speed the development of the most promising COVID-19 treatments and vaccines. 

ACTIV brings together partners from government, industry, academia, and non-profit organizations. 

NIH urged individuals interested in learning more about ACTIV to visit the ACTIV Therapeutics page.

The National Center for Advancing Translation Sciences (NCATS), part of NIH, will oversee the trial with funding support from the Biomedical Advanced Research and Development Authority (BARDA) of the HHS Office of the Assistant Secretary for Preparedness and Response. 
The trial is in support of the Trump Administration’s Operation Warp Speed, a public-private partnership to facilitate the development, manufacturing, and distribution of COVID-19 countermeasures, including vaccines, therapeutics, and diagnostics, between components of HHS.