A randomized controlled trial of an intravenous SARS-CoV-2 protease inhibitor PF-07304814 for hospitalized COVID-19 patients

Background Antiviral treatment options for hospitalized COVID-19 patients are limited. Methods We conducted a phase 2/3, randomized, placebo-controlled clinical trial of PF-07304814, an intravenous SARS-CoV-2 protease inhibitor. From September-December 2021, adults hospitalized for COVID-19 were randomized to continuous intravenous infusion of PF-07304814 (250 mg/24 hours) or placebo for 120-hours (or hospital discharge). The primary outcome was time to sustained recovery through day 90. The primary safety outcome through day 28 was a composite of death, serious adverse events, organ failure, thromboembolic events (pre-specified as events of special interest), serious infections, and grade 3/4 adverse events. Results We randomized 58 participants (32 PF-07304814; 26 placebo). After three participants experienced serious adverse events (SAEs), two related to thromboembolic events and one to acute abdominal pain, the trial was put on hold by regulators and thereafter administratively closed. The composite safety outcome through day 28 occurred in 17/32 (53%) participants assigned PF-07304814 and 11/26 (42%) participants assigned placebo (hazard ratio (HR) 1.20, 95% CI 0.56–2.57; p = 0.64). The estimated cumulative incidence of sustained recovery at day 90 was 75% for PF-07304814 and 50% for placebo participants (sHR 1.41; 95% CI: 0.71–2.80). In the PF-07304814 arm, 4 (12.5%) experienced a thromboembolic event; all died by day 90. In the placebo arm, 2 (7.7%) experienced a thromboembolic event (HR 1.46, 95% CI 0.27–7.95); both survived to the end of follow-up. Conclusion The risk/benefit of PF-07304814 could not be established due to early termination of enrollment. Rates of thromboembolic events with PF-07304814 were not statistically different than placebo. Trial Registration TICO ClinicalTrials.gov number, NCT04501978, Registration date: August 6, 2020. Keypoints The safety and efficacy of an intravenous SARS-CoV-2 protease inhibitor PF-07304814 could not be established in this randomized controlled trial of 58 participants. These results provide preliminary data for testing other protease inhibitors and antiviral medications in hospitalized COVID-19 patients.