STRIVE Trial 1: Shionogi Protease Inhibitor (S-217622)
The STRIVE Trial 1 generated high-quality data from more than 600 participants enrolled through a large international research network. The study provided important evidence that, despite demonstrating antiviral activity, ensitrelvir did not improve clinical outcomes for adults hospitalised with COVID-19 when added to standard of care. These findings contribute to the global evidence base for COVID-19 therapeutics and highlight the importance of large randomised clinical trials in identifying effective treatments for serious respiratory viral infections.
Outcomes among hospitalised patients infected with SARS-CoV-2, including and especially those with critical disease, remain poor. Given the ongoing clinical need for improved treatments for hospitalised patients and the evidence for ongoing viral replication in this cohort, new antiviral agents including direct-acting antiviral (DAA), are an important priority for additional investigation.
This COVID-19 treatment study is designed to evaluate the safety and efficacy of S-217622, an anti-SARS-CoV-2 3C-like protease inhibitor developed by Shionogi & Co. Ltd.S-217622 (ensitrelvir), when given in addition to standard of care in patients hospitalised for the medical management of COVID-19. By potentially reducing mortality and recovery times, the project aims to offer a new, effective treatment option, significantly impacting patient outcomes for hospitalised patients with COVID-19 symptoms. This large-scale study plans to recruit 1,500 participants at over 250 sites across more than 30 countries.
This is a phase III, randomised, double-blinded, placebo-controlled, multi-center international clinical trial. Randomization to S-217622 plus SOC or matched placebo plus SOC in a 1:1 allocation. Study investigational agent/placebo will be administered as oral tablets for five days. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4. The SOC will be determined by local established guidelines and may include additional DAA (e.g., remdesivir) and immunomodulatory treatment strategies. Certain SOC treatments will be pre-specified prior to randomization. An independent data and safety monitoring board will regularly review interim safety and efficacy data of this trial.
The STRIVE Trial 1 enrolled 602 participants across an international network of clinical sites. Results showed that while ensitrelvir demonstrated antiviral activity against SARS-CoV-2, it did not improve clinical recovery or other clinical outcomes when added to standard of care for hospitalised adults with COVID-19. No differences were observed in the primary safety outcome between the treatment and placebo groups. The study findings were published in Clinical Infectious Diseases in April 2026.
- International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
- University of Minnesota – Clinical and Translational Science Institute – Minnesota, USA
- Copenhagen HIV Program (CHIP) – Copenhagen, Denmark
- Medical Research Council (MRC) CTU at University College London (UCL) London, United Kingdom
- The Institute for Clinical Research at the Veterans Affairs Medical Center – Washington, D.C, USA
- Hennepin Medical Center - Minneapolis, Minnesota, USA
- Mount Sinai Medical Center, New York, New York, USA
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
- US Department of Veterans Affairs, USA
National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
