Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial
Issued Date
2025-06-15
Resource Type
ISSN
10584838
eISSN
15376591
Scopus ID
2-s2.0-105011246829
Pubmed ID
39960062
Journal Title
Clinical Infectious Diseases
Volume
80
Issue
6
Start Page
1235
End Page
1244
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Infectious Diseases Vol.80 No.6 (2025) , 1235-1244
Suggested Citation
Luetkemeyer A.F., Chew K.W., Lacey S., Hughes M.D., Harrison L.J., Daar E.S., Eron J., Fletcher C.V., Greninger A.L., Hessinger D., Li J.Z., Mailhot D., Wohl D., Chayakulkeeree M., Mendoza J.L.A., Elistratova P., Makinde O., Morgan G., Portsmouth S., Uehara T., Smith D., Currier J.S. Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial. Clinical Infectious Diseases Vol.80 No.6 (2025) , 1235-1244. 1244. doi:10.1093/cid/ciaf029 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/111427
Title
Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial
Author's Affiliation
Harvard Medical School
University of Washington
University of California, San Diego
The University of North Carolina at Chapel Hill
UCSF School of Medicine
David Geffen School of Medicine at UCLA
University of Nebraska Medical Center
National Institute of Allergy and Infectious Diseases (NIAID)
Harbor-UCLA Medical Center
Siriraj Hospital
Shionogi & Co., Ltd.
Center for Biostatistics in AIDS Research
IPS Centro Científico Asistencial
University of Washington
University of California, San Diego
The University of North Carolina at Chapel Hill
UCSF School of Medicine
David Geffen School of Medicine at UCLA
University of Nebraska Medical Center
National Institute of Allergy and Infectious Diseases (NIAID)
Harbor-UCLA Medical Center
Siriraj Hospital
Shionogi & Co., Ltd.
Center for Biostatistics in AIDS Research
IPS Centro Científico Asistencial
Corresponding Author(s)
Other Contributor(s)
Abstract
Background Ensitrelvir, a severe acute respiratory syndrome coronavirus-2 main protease inhibitor, has demonstrated clinical and virologic efficacy in previous studies. Methods In this global phase 3 trial, nonhospitalized adults with mild-to-moderate coronavirus disease 2019 (COVID-19) and symptom onset within 5 days were randomized (1:1) to receive once-daily ensitrelvir (375 mg day 1, 125 mg days 2-5) or blinded matching placebo. The primary endpoint was the restricted mean time to sustained (≥2 days) resolution of 15 COVID-19 symptoms, recorded in participant daily diaries, through day 29 in participants starting treatment within 3 days after symptom onset. Virologic efficacy and safety were assessed. Results Of 2093 participants, 1888 started treatment within 3 days after symptom onset. Mean time to symptom resolution was 12.5 and 13.1 days with ensitrelvir and placebo, respectively (difference, -0.6 days; 95% confidence interval, -1.38 to 0.19; P =. 14). On day 4, ensitrelvir reduced least-squares mean RNA by 0.72 log10 copies/mL more than placebo (95% confidence interval, 0.55-0.90). Among those with positive viral cultures at enrollment, 274/287 (95.5%) ensitrelvir-treated versus 210/280 (75.0%) placebo-treated participants had negative cultures on day 4. RNA rebound was similar (<1.5%) between groups. The proportion of participants with ≥1 adverse event was similar with ensitrelvir (61.5%) and placebo (60.6%). No treatment-related serious adverse events or deaths occurred. Three (0.3%) ensitrelvir-treated and 1 (0.1%) placebo-treated participants had COVID-19-related hospitalizations by day 29. Conclusions Despite the evidence of antiviral activity with ensitrelvir, this trial did not demonstrate a significant difference in time to sustained symptom resolution.