Newswise — Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, today announced the addition of a new agent to the ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial. This phase 2 study, which is being led by the ACTG, will evaluate the combination of the two monoclonal antibodies BRII-196 and BRII-198 to treat early COVID-19. ACTIV-2 includes both phase 2 and phase 3 evaluations of multiple promising investigational agents for treating early, symptomatic COVID-19 in a single trial. For information about enrolling in the trial, please visit the study website.
BRII-196 and BRII-198 (developed by Brii Biosciences) were derived from antibodies made by people who had recovered from COVID-19. Because BRII-196 and BRII-198 target two different parts of SARS-CoV-2 (the virus that causes COVID-19), the hope is that the combination therapy will improve treatment efficacy and reduce the likelihood that the virus will develop resistance to the treatment.
“We are excited to add BRII-196 and BRII-198 to ACTIV-2 and to investigate combination monoclonal antibody treatment,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles (UCLA). “While we are thrilled that vaccines to prevent COVID-19 are becoming available, we will continue to need treatments for those who develop COVID-19. Our goal is to increase our understanding of the best ways to treat early COVID-19.”
Participants will be randomized to receive either BRII-196 and BRII-198 (1000 mg each, administered as two separate infusions as a one-time dose) or placebo. As in all ACTIV-2 phase 2 studies, BRII-196 and BRII-198 will be evaluated to determine safety, antiviral activity, and ability to reduce the duration of COVID-19 symptoms over 28 days. Researchers will also assess the correlation between changes in viral shedding and clinical outcomes, leading to a better understanding of whether effective medications can reduce or halt the transmission of SARS-CoV-2 to others.
ACTIV-2 has progressed on an unprecedented timeline. The ACTG received approval to develop an adaptive master platform trial for outpatients in May 2020 and enrolled the first participant less than 15 weeks later. Following intensive efforts to set up outpatient treatment sites, there are now 88 active U.S. sites, which are enrolling briskly. Thus far, ACTIV-2 has completed a phase 2 study of bamlanivimab (also a monoclonal antibody) and is evaluating several additional agents for potential inclusion (infusions, intramuscular injections, inhaled agents, and oral agents).
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 is also receiving support from Operation Warp Speed, the U.S. government’s multi-agency effort to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.
To qualify for ACTIV-2, participants must have tested positive for SARS-CoV-2 in the outpatient setting and started experiencing symptoms within 10 days of enrolling. All participants eligible to participate in the study of BRII-196 and BRII-198 will have a risk factor that puts them at higher risk of progressing to severe COVID-19, including being age 60 or older, being a current smoker, or having one of the following conditions: chronic lung, kidney, or liver disease; obesity; hypertension; cardiovascular disease; diabetes; or current cancer or immunosuppression.
The ACTG is committed to enrolling individuals most impacted by COVID-19. To date, nearly a third of ACTIV-2 participants have been Latinx and the ACTG has launched initiatives to increase inclusion of people of color, including establishing research sites in locations where Black, Latinx, Asian, and Native American individuals receive care.
The study of BRII-196 and BRII-198 is led by Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center and Teresa H. Evering, M.D., M.S., Weill Cornell Medicine. 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 supported by Dr. Currier and ACTG Co-Chair Joseph J. Eron, M.D., University of North Carolina.
“COVID-19 continues to have a devastating effect on people around the world,” said Dr. Daar. “It has especially impacted communities of color, who are disproportionately acquiring, being hospitalized with, and dying from COVID-19. We are doing everything in our power to enroll participants from these communities to ensure that the treatments are safe and effective for the populations most impacted by the disease.”
ACTIV-2 is a randomized, blinded, controlled adaptive platform that allows promising investigational agents to be added and removed over the course of the study, in order to efficiently test a variety of new agents against placebo within the same trial infrastructure. For more information about ACTIV-2, please visit the study website or www.actgnetwork.org.
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