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
Mukae et al.
, Efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19: the phase 2b part of a..
, Clinical Infectious Diseases, doi:10.1093/cid/ciac933, jRCT2031210350
RCT 428 COVID-19 patients in Japan showing faster viral clearance and improved recovery with ensitrelvir.
relative improvement in symptom score, 9.2% better, RR 0.91, p = 0.28, treatment mean 5.42 (±3.7) n=116, control mean 4.92 (±3.25) n=111, 250mg, Table 2.
relative improvement in symptom score, 17.3% better, RR 0.83, p = 0.04, treatment mean 5.95 (±4.02) n=114, control mean 4.92 (±3.25) n=111, 125mg, Table 2.
time to viral-, 32.4% lower, relative time 0.68, p < 0.001, treatment 113, control 108, relative time to first negative viral titer, 250mg, Figure 3.
time to viral-, 44.2% lower, relative time 0.56, p < 0.001, treatment 113, control 108, relative time to first negative viral titer, 125mg, Figure 3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mukae et al., 7 Dec 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Japan, peer-reviewed, 11 authors, study period 2 January, 2022 - 9 February, 2022, trial jRCT2031210350
Abstract: Clinical Infectious Diseases
Efficacy and safety of ensitrelvir in patients with mild-tomoderate COVID-19: the phase 2b part of a randomized,
placebo-controlled, phase 2/3 study
Hiroshi Mukae1, Hiroshi Yotsuyanagi2, Norio Ohmagari3, Yohei Doi4,5, Hiroki Sakaguchi6,
Takuhiro Sonoyama6, Genki Ichihashi6, Takao Sanaki7, Keiko Baba7, Yuko Tsuge6, Takeki
Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical
Sciences, Nagasaki, Japan; 2The Institute of Medical Science, The University of Tokyo, Tokyo,
Japan; 3Disease Control and Prevention Center, National Center for Global Health and Medicine,
Tokyo, Japan; 4Division of Infectious Diseases, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania, USA; 5Departments of Microbiology and Infectious Diseases, Fujita
Health University School of Medicine, Toyoake, Japan; 6Drug Development and Regulatory
Science Division, Shionogi & Co., Ltd., Osaka, Japan; 7Pharmaceutical Research Division,
Shionogi & Co., Ltd., Toyonaka, Japan
Background. This phase 2b part of a randomized phase 2/3 study assessed the efficacy and
safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the
*Corresponding author: Takeki Uehara Drug Development and Regulatory Science Division,
Shionogi & Co., Ltd. Address: 8F, Nissay Yodoyabashi East, 3-3-13 Imabashi, Chuo-ku, Osaka
541-0042, Japan Email: email@example.com
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases
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Methods. Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg
(375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The
co-primary endpoints were the change from baseline in the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up
to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed
through adverse events.
Results. A total of 341 patients (ensitrelvir 125 mg group, 114; ensitrelvir 250 mg group, 116;
and placebo group, 111; male, 53.5%–64.9%; mean age, 35.3–37.3 years) were included in the
efficacy analyses. The change from baseline in the SARS-CoV-2 titer on day 4 was significantly
greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10
50% tissue-culture infectious dose/mL, P<0.0001 for both). The total score of the 12 COVID-19
symptoms did not show a significant difference between the ensitrelvir groups and placebo
group. The time-weighted average change from baseline up to 120 hours was significantly
greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and
respiratory symptoms. Most adverse events were mild in severity.
Conclusions. Ensitrelvir treatment demonstrated a..
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