Washington University School of Medicine (WUSM) in St. Louis now leads a Phase 3 clinical trial, funded by the National Institutes of Health (NIH), testing the potential of three inflammatory disease-drugs in a bid to address and treat the cytokine storm associated with the novel coronavirus as well as shorten hospital stays and reduce the need for dependence on ventilators to augment breathing.
SARS-CoV-2 has been associated with autoimmune disease-like conditions once a patient is done with the viral infection. For months after, an individual’s immune system can produce immune proteins at the already vanquished virus, writes Julia Evangelou Strait for the WUSM St. Louis News Hub. This reaction can lead to dangerous conditions such as the cytokine storm, which can add to acute respiratory distress syndrome (ADDS) and multiple organ failure, and ultimately death.
William G. Powderly, MD, protocol chair of the international trial and also the J. William Campbell Professor of Medicine and director of the Institute of Clinical and Translational Sciences, commented on this situation, noting, “In severe COVID-19 infection, we think the virus triggers an abnormal immune response, which drives inflammation in the lungs and is the major reason people end up needing ventilators and sometimes dying.”
Dr. Powderly continued, “The viral infection can trigger the need for hospitalization, but the illness that we see in such patients is predominantly an aberrant immune response. About ten days after the initial infection—around the time many people with severe illness are hospitalized—many don’t have the virus anymore, so any antiviral drug can’t do much at this point. We think adding an immune modulator drug may be helpful, and this is designed to determine whether such drugs can benefit patients with severe illness.”
Now, WUSM St. Louis leads a clinical trial enrolling a target of 2,000 patients hospitalized with moderate to severe SARS-CoV-2 around the United States and Latin America. Patients will receive the standard of care treatment (SoC), including remdesivir, which was approved via emergency use authorization as it reduced in one study hospitalization duration from 14 days to 11 days. In addition to SoC, the study team will assign either a placebo or one of three anti-inflammatory drugs.
Sponsored by NIH and part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative and is coordinated by the National Center for Advancing Translational Sciences (NCATS), part of NIH. It’s expected to run for six months and will involve eligible and consenting patients at Barnes-Jewish Hospital.
Note that this study is based on an adaptive master protocol design affording the investigators the flexibility to investigate up to five drugs at one time; they can also stop or proceed with certain drugs based on evidence in the trial. Those drugs that don’t show promise can be terminated upon the appropriate evidence.
Moreover, the standard of care can transform based on evidence.
The study team will use the following study drugs:
- Infliximab (Remicade/Janssen Research & Development LLC—one of the Janssen Pharmaceutical Companies of Johnson & Johnson).
- Abatacept (Orencia/Bristol Myers Squibb).
- Cenicriviroc (the investigational drug under development by AbbVie).
All three of these drugs were designed to curb the immune system and reduce inflammation. While Infliximab has been approved by the FDA to treat several chronic inflammatory conditions (e.g., rheumatoid arthritis and Crohn’s disease), Abatacept is also FDA approved for similar conditions, while the AbbVie drug is still under study for liver inflammation trigger by fat buildup in the liver and has been evaluated for HIV infection.
What is ACTIV?
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative is a public-private partnership, with funding provided by Operation Warp Speed through the Biomedical Advanced Research and Development Authority of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. Although a critically important centralizing and organizing entity to support COVID-19 clinical trials, TrialSite also observed ways it could diversify its leadership and core participation.