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All Studies   Meta Analysis    Recent:   

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

May 2022  
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0 0.5 1 1.5 2+ Change in viral titer, 250mg 45% primary Improvement Relative Risk Change in viral titer, 125mg 36% primary Time to viral-, 125mg 45% Time to viral-, 250mg 44% Viral clearance, 250mg, da.. 54% Viral clearance, 125mg, da.. -10% Viral clearance, 250mg.. (b) 80% Viral clearance, 125mg.. (b) 54% Viral clearance, 250mg.. (c) 54% Viral clearance, 125mg.. (c) 90% Viral clearance, 250mg.. (d) 80% Viral clearance, 125mg.. (d) 63% Viral clearance, 250mg.. (e) 9% Viral clearance, 125mg.. (e) -10% Ensitrelvir  Mukae et al.  EARLY TREATMENT  DB RCT Is early treatment with ensitrelvir beneficial for COVID-19? Double-blind RCT 69 patients in Japan (September 2021 - January 2022) Improved viral clearance with ensitrelvir (p=0.0025) c19early.org Mukae et al., medRxiv, May 2022 Favors ensitrelvir Favors control
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).
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.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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 PaperEnsitrelvirAll
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
All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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On day 4, the change from baseline in SARS-CoV-2 viral titer ' '(log<jats:sub>10</jats:sub> 50% tissue culture infectious dose/mL) in patients with positive ' 'viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard ' 'deviation], −2.42 [1.42]; <jats:italic>P</jats:italic> = 0.0712) and 250 mg (−2.81 [1.21]; ' '<jats:italic>P</jats:italic> = 0.0083) versus placebo (−1.54 [0.74]), and ensitrelvir ' 'treatment reduced SARS-CoV-2 RNA by −1.4 to −1.5 log<jats:sub>10</jats:sub> copies/mL versus ' 'placebo. All adverse events were mild to moderate. 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