The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which recently expanded its focus to include evaluating outpatient treatment for COVID-19, today announced that Teresa H. Evering, M.D., M.S., a co-lead investigator (with Eric S. Daar, M.D.) for BRII-196/BRII-198 in the ACTIV-2 study of Outpatient Monoclonal Antibodies and Other Therapies, will present data for the monoclonal antibody combination at the virtual IDWeek 2021 conference, taking place September 29 – October 3, 2021.
“As SARS-CoV-2, the virus that causes COVID-19, continues to spread, there remains a significant need to develop safe and effective therapeutics that prevent severe disease,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “This presentation demonstrates that BRII-196/BRII-198 was safe, well-tolerated, and demonstrated a significant reduction in the risk of hospitalization and death among adults with mild to moderate COVID-19 who were high risk of progressing to severe disease. We are excited to present data highlighting a new therapeutic with the potential to help attenuate the impact of this pandemic.”
BRII-196 and BRII-198 (developed by Brii Biosciences) were derived from antibodies isolated from people who had recovered from COVID-19. Administered as two separate infusions as a one-time dose, they target two different parts of SARS-CoV-2. In an interim analysis, the combination demonstrated a 78 percent reduction in the combined endpoint of hospitalization and death compared with placebo in 837 non-hospitalized participants with COVID-19 who were at high risk of clinical progression. In the ACTIV-2 arm receiving BRII-196/BRII-198, there were 12 hospitalizations and one death, compared to 45 hospitalizations and nine deaths in the arm receiving placebo [2.4 vs. 11.1 percent, relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001]. Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8 percent vs. 13.4 percent), with no severe infusion reactions or drug-related serious AEs. Notably, the clinical benefit was similar among participants who entered the study after having five or fewer days of symptoms and those who had experieinced symptoms for more than five days.
Between January and July 2021, ACTIV-2 enrolled participants from sites in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines who were randomized to receive either BRII-196/BRII-198 or placebo. The median participant age was 49 years; 51 percent of participants were female, 17 percent were Black, and 49 percent were Hispanic. In this interim analysis, 71 percent of participants had a day 28 visit and 97 percent had a day seven visit.
ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising therapies to be added and removed over the course of the study to efficiently test a variety of new agents against placebo within the same trial infrastructure. In addition to studying the safety and efficacy of investigational therapies, ACTIV-2 also aims to determine whether they can decrease viral shedding, thereby potentially preventing transmission of SARS-CoV-2.
ACTIV-2 is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG. ACTIV-2 is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from the Federal COVID Response – Therapeutics, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics. The phase 3 trial is a continuation of the phase 2 trial in which BRII-196/BRII-198 met study-defined safety and efficacy criteria.
ACTIV-2 is led by Kara Chew, M.D., M.S., UCLA and Davey Smith, M.D., University of California San Diego (protocol chairs) and David Alain Wohl, M.D., University of North Carolina (UNC) and Dr. Daar, Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs), and supported by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Co-Chair).
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