Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild-to-Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial

Yotsuyanagi et al., medRxiv, doi:10.1101/2023.07.11.23292264, SCORPIO-SR, jRCT2031210350

Jul 2023

Source PDF All Studies Meta AnalysisMeta

RCT 1,821 COVID-19 outpatients in Japan, Vietnam, and South Korea, showing improved viral clearance and improved recovery (significant for patients treated within 3 days of onset) with ensitrelvir. Only 2 hospitalizations were reported, with no deaths.

Important missing comments or errors? Let us know.

risk of hospitalization, 0.8% higher, RR 1.01, p = 1.00, treatment 1 of 595 (0.2%), control 1 of 600 (0.2%), 250mg.

risk of hospitalization, 66.7% lower, RR 0.33, p = 0.50, treatment 0 of 603 (0.0%), control 1 of 600 (0.2%), NNT 600, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), 125mg.

recovery time, 11.4% lower, relative time 0.89, p = 0.30, treatment 577, control 572, 14 symptoms, randomized within 120 hours, 250mg.

recovery time, 10.1% lower, relative time 0.90, p = 0.46, treatment 582, control 572, 14 symptoms, randomized within 120 hours, 125mg.

recovery time, 17.9% lower, relative time 0.82, p = 0.05, treatment 330, control 321, 14 symptoms, randomized within 72 hours, 250mg.

recovery time, 19.0% lower, relative time 0.81, p = 0.03, treatment 336, control 321, 14 symptoms, randomized within 72 hours, 125mg.

recovery time, 13.3% lower, relative time 0.87, p = 0.35, treatment 577, control 572, 12 symptoms, randomized within 120 hours, 250mg.

recovery time, 9.7% lower, relative time 0.90, p = 0.76, treatment 582, control 572, 12 symptoms, randomized within 120 hours, 125mg.

recovery time, 13.3% lower, relative time 0.87, p = 0.08, treatment 330, control 321, 12 symptoms, randomized within 72 hours, 250mg.

recovery time, 15.9% lower, relative time 0.84, p = 0.07, treatment 336, control 321, 12 symptoms, randomized within 72 hours, 125mg.

relative change in viral load, 48.8% better, RR 0.51, p < 0.001, treatment 579, control 589, randomized within 120 hours, 250mg.

relative change in viral load, 48.8% better, RR 0.51, p < 0.001, treatment 592, control 589, randomized within 120 hours, 125mg.

relative change in viral load, 59.4% better, RR 0.41, p < 0.001, treatment 330, control 321, randomized within 72 hours, 250mg.

relative change in viral load, 59.3% better, RR 0.41, p < 0.001, treatment 336, control 321, randomized within 72 hours, 125mg.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Yotsuyanagi et al., 13 Jul 2023, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, preprint, mean age 35.7, 13 authors, study period 10 February, 2022 - 10 July, 2022, trial jRCT2031210350 (SCORPIO-SR).

Contact: takeki.uehara@shionogi.co.jp.

All Studies All Outcomes Submit Updates or Corrections

This Paper Ensitrelvir All

Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild-to-Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial

M.D Hiroshi Yotsuyanagi, M.D Norio Ohmagari, M.D Yohei Doi, M.D Masaya Yamato, M.D Nguyen Hoang Bac, M.D Bong Ki Cha, M.S Takumi Imamura, M.D Takuhiro Sonoyama, Genki Ichihashi, Ph.D Takao Sanaki, M.S Yuko Tsuge, Ph.D Takeki Uehara, M.D Hiroshi Mukae

doi:10.1101/2023.07.11.23292264

IMPORTANCE Treatment options for coronavirus disease 2019 (COVID-19) that can be used irrespective of risk factors for severe disease are warranted. OBJECTIVE To assess the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19. DESIGN The phase 3 part of a phase 2/3, double-blind, randomized, placebo-controlled study conducted from February 10 to July 10, 2022. SETTING A multicenter study conducted at 92 institutions in Japan, Vietnam, and South Korea. PARTICIPANTS Patients (aged 12 to <70 years) with mild-to-moderate COVID-19 within 120 hours of positive viral testing. INTERVENTIONS Patients were randomized (1:1:1) to receive once-daily ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or placebo for 5 days. Among 1821 randomized patients, 1030 (347, 340, and 343 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were randomized in less than 72 hours of disease onset and assessed as the primary analysis population. MAIN OUTCOMES AND MEASURES The primary end point was the time to resolution of five COVID-19 symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness). Other end points included virologic efficacy and safety. RESULTS The mean age was 35.7, 35.3, and 34.7 years, and 193 (55.6%), 185 (54.4%), and 174 (50.7%) patients were men in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (intention-to-treat, primary analysis population). A significant difference (P=.04 with a Peto-Prentice generalized Wilcoxon test stratified by vaccination history) was observed in the primary end point between ensitrelvir 125 mg and placebo in the primary

References

Ancova, analysis of covariance; CI, confidence interval; COVID-19, coronavirus disease 2019; LS, least squares; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SE, standard error

Auvigne, Vaux, Strat, Severe hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants in France, EClinicalMedicine

Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -final report, N Engl J Med

Bernal, Da Silva, Musungaie, Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, N Engl J Med

Butler, Hobbs, Gbinigie, Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial, Lancet

Clinicaltrials, Gov, Evaluation of protease inhibition for COVID-19 in standard-risk patients (EPIC-SR)

Covid-19, RNA, ribonucleic acid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

Hammond, Leister-Tebbe, Gardner, Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19, N Engl J Med

Hammond, Leister-Tebbe, Gardner, Sustained alleviation and resolution of targeted COVID-19 symptoms with nirmatrelvir/ritonavir versus placebo, Open Forum Infect Dis, doi:10.1093/ofid/ofac492.994

Hyams, Challen, Marlow, Severity of Omicron (B.1.1.529) and Delta

Kawashima, Matsui, Adachi, Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally, Biochem Biophys Res Commun

Kopsidas, Karagiannidou, Kostaki, Global distribution, dispersal patterns, and trend of several Omicron subvariants of SARS-CoV-2 across the globe, Trop Med Infect Dis

Meng, Abdullahi, Ferreira, Altered TMPRSS2 usage by

Mukae, Yotsuyanagi, Ohmagari, A randomized phase 2/3 study of ensitrelvir, a novel oral SARS-CoV-2 3C-like protease inhibitor, in Japanese patients with mildto-moderate COVID-19 or asymptomatic SARS-CoV-2 infection: results of the phase 2a part, Antimicrob Agents Chemother

Mukae, Yotsuyanagi, Ohmagari, Efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19: the phase 2b part of a randomized, placebo-controlled, phase 2/3 study, Clin Infect Dis, doi:10.1093/cid/ciac933

Najjar-Debbiny, Gronich, Weber, Effectiveness of molnupiravir in high-risk patients: a propensity score matched analysis, Clin Infect Dis

Nyberg, Ferguson, Nash, Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study, Lancet

Sasaki, Tabata, Kishimoto, S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters, Sci Transl Med

Shimizu, Sonoyama, Fukuhara, Kuwata, Matsuo et al., Safety, tolerability, and pharmacokinetics of the novel antiviral agent ensitrelvir fumaric acid, a SARS-CoV-2 3CL protease inhibitor, in healthy adults, Antimicrob Agents Chemother

Takashita, Yamayoshi, Simon, Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants, N Engl J Med

Unoh, Uehara, Nakahara, Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19, J Med Chem

Uraki, Ito, Kiso, Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate, Lancet Infect Dis, doi:10.1016/S1473-3099(23)00070-1

Uraki, Kiso, Iida, Characterization and antiviral susceptibility of

Wolter, Jassat, Walaza, Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study, Lancet

Yamasoba, Kosugi, Kimura, Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to therapeutic monoclonal antibodies, Lancet Infect Dis

Yotsuyanagi, Ohmagari, Doi, A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (phase 3 part), Medicine (Baltimore)

Download Image

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

@CovidAnalysis

FAQ

Public domain CC0 1.0