NIH Trials Enrolling People Hospitalized with COVID-19
December 17, 2020
A scanning electron micrograph shows an apopototic cell (colored red) heavily infected with SARS-CoV-2 virus particles (colored yellow)
A scanning electron micrograph shows an apopototic cell (colored red) heavily infected with SARS-CoV-2 virus particles (colored yellow)
Two randomized, controlled Phase 3 clinical trials have begun evaluating investigational monoclonal antibodies for their safety and efficacy in treating people hospitalized with COVID-19. The trials are part of the ACTIV-3 master protocol, which has an adaptive design allowing investigators to add new sub-studies of additional investigational agents. ACTIV-3 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
One sub-study is evaluating VIR-7831, a monoclonal antibody developed through a partnership between GlaxoSmithKline (Brentford, United Kingdom) and Vir Biotechnology, Inc. (San Francisco). The other sub-study is evaluating the combination of BRII-196 and BRII-198, two neutralizing monoclonal antibodies manufactured by Brii Biosciences (Durham, N.C. and Beijing). Antibodies are infection-fighting proteins naturally made by the immune system. Antibodies can prevent viruses from infecting cells, sometimes by binding to the surface of the viruses. Synthetic versions of these antibodies, prepared in a laboratory, are known as monoclonal antibodies.
Participants in the new ACTIV-3 sub-studies will share a control group and be randomized 1:1:1 to receive either a saline placebo control, VIR-7831 or the Brii combination. Initially, researchers will enroll approximately 450 volunteers (150 per group) who have been hospitalized with mild-to-moderate COVID-19 with fewer than 13 days of symptoms. After five days, the participants’ medical condition will be assessed on two 7-point ordinal scales, each ranging from being able to undertake usual activities with minimal or no symptoms, to death.
If both VIR-7831 and the Brii combination appear to be safe and effective, based on the ordinal outcomes assessed at five days, enrollment in the trial will be expanded. An additional 1,050 participants will be enrolled and randomized to the three groups, for a total of 1,500 participants enrolled by the trial’s conclusion. These additional enrollments may include participants with more severe illness, so that researchers can evaluate the primary endpoint of sustained recovery. Participants will have met this endpoint when they have been discharged from the hospital and lived at home for 14 consecutive days, prior to 90 days of follow-up.
Prior to the addition of these therapeutics to the trial, ACTIV-3 previously tested a different monoclonal antibody known as LY-CoV555, developed by Eli Lilly and Company (Indianapolis). Following a recommendation from the Data and Safety Monitoring Board (DSMB) for this trial, ACTIV-3 investigators recently closed the sub-study, based on the low likelihood that the intervention would be of clinical value to the hospitalized patients in the study.
ACTIV-3 is part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines.
The VIR/GSK sub-study also is receiving funding support through Operation Warp Speed, the U.S. government’s multi-agency effort to develop, manufacture and distribute medical countermeasures for COVID-19. The Brii sub-study is supported by funding from NIAID.
People interested in learning more about the trial can visit clinicaltrials.gov and search identifier NCT04501978.