The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), continues to invest resources into novel monoclonal antibody-based investigational products targeting COVID-19 via the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program in this case ACTIV-2, a master protocol designed for evaluating multiple investigational agents compared to placebo in adults with mild to moderate COVID-19. This study, led by the NIAID-funded trial site network known as AIDS Clinical Trials Group (ACTG) and supported by a top contract research organization (CRO) PPD will enroll patients around the world. The Phase 2/3 study initiated and investigates a combination of two monoclonal antibodies including BRII-196 and BRII-198 targeting SARS-CoV-2. These products are developed by a company based out of the People Republic of China called Brii Biosciences. The company’s founder, a prominent pharmaceutical executive based in Research Triangle, is active in public health circles around the globe.
The ACTIV-2 study began on Aug. 4, 2020, with an evaluation of LY-CoV555, an investigational monoclonal antibody discovered by AbCellera Biologics (Vancouver, British Columbia) in collaboration with NIAID’s Vaccine Research Center. LY-CoV555 was developed further and manufactured by Eli Lilly and Company (Indianapolis, Indiana), in partnership with AbCellera. On Nov. 10, 2020, LY-CoV555, also known as bamlanivimab, was granted Emergency Use Authorization by the U.S. Food and Drug Administration for treating mild-to-moderate COVID-19 in adults and children over 12 years old who are at high risk for progressing to severe COVID-19 and/or hospitalization. With the initiation of the BRII-196 and BRII-198 experimental monoclonal antibodies in the ACTIV-2 study, the LY-COV555 sub-study will close to enrollment.
What are BRII-196 and BRII-198?
BRII-196 and BRII-198 are investigational, neutralizing monoclonal antibodies manufactured by Brii Biosciences (Durham, North Carolina, and Beijing). Antibodies are infection-fighting proteins naturally made by the immune system that can bind to viruses and prevent them from infecting cells. BRII-196 and BRII-198 are synthetic versions of antibodies produced naturally by humans. Data on each antibody from Phase I trials that are currently ongoing support the doses being used in the ACTIV-2 trial.
The ACTIV-2 study design allows researchers to observe the therapeutics’ efficacy in a small group of volunteers and then administer it to a larger group if the antibody appears safe and effective. The trial will initially enroll 220 participants with mild or moderate COVID-19, who are at risk for disease progression. Half of the participants (110) will receive BRII-196 and BRII-198 through intravenous infusions, while the remaining half will receive placebo infusions. Participants are assigned at random to one of the treatment groups, and the trial is blinded, so neither participants nor investigators will know who is receiving the antibody therapy. Participants will attend a series of clinic or at-home visits by clinicians to track their condition and will be followed for a total of 72 weeks.
An independent Data and Safety Monitoring Board (DSMB) overseeing the trial will review the data collected at 28 days. They will monitor data to see if the therapy is safe, can reduce the duration of COVID-19 symptoms, and can eliminate the presence of viral RNA in the body. If there are no serious safety concerns and the results seem promising, the trial will transition to Phase 3 to enroll approximately 622 additional outpatient volunteers, for a total of 842 trial participants. These new participants will be randomized to receive the therapeutic or a placebo.
The primary objective of the Phase 3 trial is to determine if the therapy prevents either hospitalization or death by 28 days after study entry.
The study team for ACTIV-2 is led by protocol chairs Kara W. Chew, M.D., M.S., of the University of California, Los Angeles (UCLA), and Davey Smith, M.D., MAS, of the University of California, San Diego. Eric S. Daar, M.D., of UCLA, and David Wohl, M.D., of the University of North Carolina at Chapel Hill (UNC), serve as protocol vice-chairs. The ACTG network is led by chair Judith Currier, M.D. (UCLA) and vice-chair Joseph Eron, M.D., of UNC. The study of BRII-196 and BRII-198 is led by Eric S. Daar, M.D., of the Harbor-UCLA Medical Center and Teresa H. Evering, M.D., M.S., of Weill Cornell Medical Center, New York City.
Based in China, Brii Biosciences is a company that focuses on serving patients and improving public health in China. Founded in 2018 the company focuses on accelerating innovation and optimizing access to the latest medicine for Chinese patients according to its LinkedIn page. The company is headquartered in China with offices in Shanghai, Beijing, San Francisco and Durham, NC, in the Research Triangle. The company has raised approximately $260 million in venture capital funding.
Dr. Zhi Hong founded the company in 2018; he spent 11 years as Senior Vice President at GlaxoSmithKline, heading the Infectious Diseases Therapy Area Unit. Dr. Hong was widely credited as the key architect of GSK’s comeback and success in the HIV and infectious disease medicine discovery and development. Dr. Hong was an active deal maker helping revitalize ViiV Healthcare’s (a joint venture between GSK, Pfizer and Shionogi) HIV business. Hong is an active public health advocate with the US/EU governments and philanthropic organizations such as the Gates Foundation and Wellcome Trust.