Los Angeles, Calif. - The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the addition of two monoclonal antibodies, BMS-986414 and BMS-986413, to the COVID-19 outpatient treatment study, ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial. BMS-986414 and BMS-986413 will be administered as subcutaneous injections (shots) given at one visit. ACTIV-2 includes both phase 2 and phase 3 evaluations of multiple investigational agents for treating early COVID-19 in a single trial. For information about enrolling in the trial, please visit the study website.
"Given that prevention and treatment will continue to be an important part of ending the COVID-19 pandemic, it is key that we identify and develop a variety of treatment options," said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). "ACTIV-2 is studying a number of different therapeutic approaches, including infusions, shots, pills, and inhalants, in an effort to ensure that everyone who gets COVID-19 has a treatment option that works for them."
BMS-986414 and BMS-986413 (developed by a partnership between Rockefeller University and Bristol Myers Squibb) were derived from antibodies from two individuals who had recovered from COVID-19. Because they target two different parts of SARS-CoV-2 (the virus that causes COVID-19), the hope is that the combination therapy will improve efficacy, cover multiple variants, and reduce the likelihood that the virus will develop resistance to the treatment.
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. Participants who enroll in ACTIV-2 will be randomly assigned to receive BMS-986414 and BMS-986413, another ACTIV-2 agent, or placebo. Other agents currently being evaluated in phase 2 include:
- SAB-185 (SAB Biotherapeutics): a polyclonal antibody infusion
- SNG001 (Synairgen): an inhaled formulation of beta interferon
- Camostat (Sagent Pharmaceuticals): an orally administered serine protease inhibitor
ACTIV-2 also currently includes a phase 3 study of BRII-196 plus BRII-198 (Brii Biosciences), two separately administered monoclonal antibody infusions. In addition, ACTIV-2 has completed enrollment for phase 2 studies evaluating AZD7442 (AstraZeneca), a combination of two monoclonal antibodies, as both a 15-minute infusion and an intramuscular injection, and has completed a phase 2 study of BRII-196 plus BRII-198.
To qualify for ACTIV-2, participants must have tested positive for SARS-CoV-2 in the outpatient setting within 10 days and started experiencing symptoms within eight days of enrolling.
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.
"In the lab, BMS-986414 and BMS-986413 have demonstrated activity against a broad range of SARS-CoV-2 variants, which is increasingly important as these variants continue to spread around the world," said Katya Corado M.D., Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of BMS-986414 and BMS-986413 in ACTIV-2. "This is the first subcutaneous injection that we've studied in ACTIV-2 and if it is effective, it will provide a treatment option for people with COVID-19 that is easier to administer and that we expect will increase access to antibody therapy."
ACTIV-2 is led by Kara W. 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 Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center (vice-chairs) and supported by Dr. Currier and Joseph J. Eron, M.D., UNC, (ACTG Co-Chair, and co-lead investigator of BMS-986414 and BMS-986413).
About the ACTG
Founded in 1987, the AIDS Clinical Trials Group (ACTG) was the world's first HIV research network. The ACTG conducts groundbreaking studies to improve the treatment of HIV and its complications, including tuberculosis and viral hepatitis; reduce new infections and HIV-related illness; and advance new approaches to prevent, treat, and ultimately cure HIV in adults and children. ACTG investigators and research units in 15 countries serve as major resources for HIV/AIDS research, treatment, care, and training/education in their communities. ACTG studies have helped establish current paradigms for managing HIV disease, and have informed HIV treatment guidelines, resulting in dramatic decreases in HIV-related mortality worldwide.