A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-like Protease Inhibitor, in Japanese Patients With Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part

Mukae et al., medRxiv, doi:10.1101/2022.05.17.22275027, jRCT2031210350

May 2022

RCT 69 patients in in Japan, showing faster viral clearance with ensitrelvir. 5-day ensitrelvir (375mg on day 1 followed by 125 mg daily or 750mg on day 1 followed by 250mg daily).

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relative change in viral titer, 45.2% better, RR 0.55, p = 0.002, treatment mean 2.81 (±1.21) n=14, control mean 1.54 (±0.74) n=14, day 4, 250mg, primary outcome.

relative change in viral titer, 36.4% better, RR 0.64, p = 0.048, treatment mean 2.42 (±1.42) n=15, control mean 1.54 (±0.74) n=14, day 4, 125mg, primary outcome.

time to viral-, 44.8% lower, relative time 0.55, p = 0.02, treatment 15, control 14, 125mg.

time to viral-, 43.6% lower, relative time 0.56, p = 0.02, treatment 13, control 14, 250mg.

risk of no viral clearance, 54.2% lower, RR 0.46, p = 0.59, treatment 1 of 12 (8.3%), control 2 of 11 (18.2%), NNT 10, day 14, 250mg, Figure S1.

risk of no viral clearance, 10.0% higher, RR 1.10, p = 1.00, treatment 3 of 15 (20.0%), control 2 of 11 (18.2%), day 14, 125mg, Figure S1.

risk of no viral clearance, 80.0% lower, RR 0.20, p = 0.48, treatment 0 of 13 (0.0%), control 2 of 13 (15.4%), NNT 6.5, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 9, 250mg, Figure S1.

risk of no viral clearance, 53.6% lower, RR 0.46, p = 0.60, treatment 1 of 14 (7.1%), control 2 of 13 (15.4%), NNT 12, day 9, 125mg, Figure S1.

risk of no viral clearance, 53.6% lower, RR 0.46, p = 0.38, treatment 2 of 14 (14.3%), control 4 of 13 (30.8%), NNT 6.1, day 6, 250mg, Figure S1.

risk of no viral clearance, 89.6% lower, RR 0.10, p = 0.03, treatment 0 of 15 (0.0%), control 4 of 13 (30.8%), NNT 3.2, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 6, 125mg, Figure S1.

risk of no viral clearance, 80.0% lower, RR 0.20, p = 0.006, treatment 2 of 14 (14.3%), control 10 of 14 (71.4%), NNT 1.8, day 4, 250mg, Figure S1.

risk of no viral clearance, 62.7% lower, RR 0.37, p = 0.03, treatment 4 of 15 (26.7%), control 10 of 14 (71.4%), NNT 2.2, day 4, 125mg, Figure S1.

risk of no viral clearance, 9.1% lower, RR 0.91, p = 1.00, treatment 10 of 14 (71.4%), control 11 of 14 (78.6%), NNT 14, day 2, 250mg, Figure S1.

risk of no viral clearance, 10.3% higher, RR 1.10, p = 0.65, treatment 13 of 15 (86.7%), control 11 of 14 (78.6%), day 2, 125mg, Figure S1.

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Mukae et al., 17 May 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Japan, preprint, 13 authors, study period 28 September, 2021 - 1 January, 2022, trial jRCT2031210350. Contact: takeki.uehara@shionogi.co.jp.

This Paper Ensitrelvir All

A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-like Protease Inhibitor, in Japanese Patients With Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part

Hiroshi Mukae, Hiroshi Yotsuyanagi, Norio Ohmagari, Yohei Doi, Takumi Imamura, Takuhiro Sonoyama, Takahiro Fukuhara, Genki Ichihashi, Takao Sanaki, Keiko Baba, Yosuke Takeda, Yuko Tsuge, Takeki Uehara

doi:10.1101/2022.05.17.22275027

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