Los Angeles, Calif. – The AIDS Clinical Trials Group (ACTG), the largest global HIV research network, which expanded its focus to conduct research into COVID-19, today announced the initiation of ACTIV-2d, a global, phase 3, multicenter trial to evaluate the impact of S-217622, an investigational oral COVID-19 antiviral agent. ACTIV-2d will evaluate the safety and efficacy of S-217622 as a once-daily treatment to reduce the duration of COVID-19 symptoms in non-hospitalized adults with early COVID-19.
S-217622, a selective inhibitor of the 3CL protease (an enzyme essential for the replication of SARS-CoV-2) was created through joint research between Hokkaido University and Shionogi & Co. Ltd. Recent results from a trial conducted in Japan and Korea demonstrated that patients treated with S-217622 showed a significant and rapid decrease in viral level and culturability after the third dose of S-217622 compared to placebo. Previous clinical trials also showed that S-217622 was well-tolerated, with few treatment-related discontinuations, and no serious adverse events or death. The most common adverse events were mild headache and transient reduction in HDL cholesterol. Additionally, S-217622 has recently demonstrated high in vitro antiviral activity against the Omicron subvariants (BA.4 and BA.5), with antiviral potency against other existing variants.
ACTIV-2d is a global phase 3, multicenter, randomized, double‑blind, 24‑week study evaluating whether S-217622 is able to reduce the time it takes for COVID-19 symptoms to resolve among participants who have tested positive for SARS-CoV-2 in the outpatient setting and started experiencing symptoms within five days of enrolling. The study will include people at lower and higher risk of progression to severe COVID-19.
“S-217622 has the potential to simplify COVID-19 treatment, as it is administered once a day without a boosting agent,” said Annie Luetkemeyer, M.D., University of California, San Francisco and a lead investigator of S-217622. “As COVID-19 remains a major global concern, we need to increase our treatment options. We are hopeful that S-217622 will be an important addition to the COVID-19 treatment toolkit.”
ACTIV-2d is being conducted with trial sites in countries in Europe, South America, North America, Africa, and Asia. Approximately 1,490 participants will be randomized in a 1:1 ratio receiving either S-217622 or placebo. Participants may take locally provided COVID-19 treatment after enrollment, as long as it is compatible with S-217622.
ACTIV-2d is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), which also funds the ACTG, and is sponsored by Shionogi. ACTIV-2d is part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, a public-private partnership program set up to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines. It also receives support from 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.
ACTIV-2d is led by Kara W. Chew, M.D., M.S., University of California, Los Angeles (UCLA), Dr. Luetkemeyer, and Davey Smith, M.D., University of California, San Diego (protocol co-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 is supported by Judith Currier, M.D., M.Sc., UCLA (ACTG Chair) and Joseph J. Eron, M.D., UNC, (ACTG Co-Chair).
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. More recently, the ACTG has expanded its focus to include the evaluation of outpatient treatments for COVID-19. 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.