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

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2023, 1, 14]], 'date-time': '2023-01-14T11:14:42Z', 'timestamp': 1673694882703}, 'posted': {'date-parts': [[2022, 5, 17]]}, 'group-title': 'Infectious Diseases (except HIV/AIDS)', 'reference-count': 15, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2022, 5, 17]]}, 'abstract': '<jats:title>ABSTRACT</jats:title><jats:p>For the treatment of coronavirus disease 2019 ' '(COVID-19), antiviral agents that can achieve rapid severe acute respiratory syndrome ' 'coronavirus 2 (SARS-CoV-2) reduction are warranted. This double-blind, phase 2a part of a ' 'phase 2/3 study assessed the efficacy and safety 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. Sixty-nine patients enrolled from 56 sites were randomized ' '(1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg ' 'daily or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. ' 'The primary outcome was change from baseline in SARS-CoV-2 viral titer. A total of 16, 14, ' 'and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, ' 'respectively, were included in the intention-to-treat population (mean age: 38.8, 40.4, and ' '38.0 years, respectively). 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. Ensitrelvir treatment demonstrated rapid ' 'SARS-CoV-2 clearance and was well tolerated in patients with mild-to-moderate COVID-19 or ' 'asymptomatic SARS-CoV-2 infection (Japan Registry of Clinical Trials identifier: ' 'jRCT2031210350).</jats:p>', 'DOI': '10.1101/2022.05.17.22275027', 'type': 'posted-content', 'created': {'date-parts': [[2022, 5, 23]], 'date-time': '2022-05-23T18:33:08Z', 'timestamp': 1653330788000}, 'source': 'Crossref', 'is-referenced-by-count': 3, 'title': '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', 'prefix': '10.1101', 'author': [ {'given': 'Hiroshi', 'family': 'Mukae', 'sequence': 'first', 'affiliation': []}, {'given': 'Hiroshi', 'family': 'Yotsuyanagi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Norio', 'family': 'Ohmagari', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yohei', 'family': 'Doi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Takumi', 'family': 'Imamura', 'sequence': 'additional', 'affiliation': []}, {'given': 'Takuhiro', 'family': 'Sonoyama', 'sequence': 'additional', 'affiliation': []}, {'given': 'Takahiro', 'family': 'Fukuhara', 'sequence': 'additional', 'affiliation': []}, {'given': 'Genki', 'family': 'Ichihashi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Takao', 'family': 'Sanaki', 'sequence': 'additional', 'affiliation': []}, {'given': 'Keiko', 'family': 'Baba', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yosuke', 'family': 'Takeda', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yuko', 'family': 'Tsuge', 'sequence': 'additional', 'affiliation': []}, {'given': 'Takeki', 'family': 'Uehara', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2022052309232260000_2022.05.17.22275027v1.1', 'doi-asserted-by': 'crossref', 'first-page': '655', 'DOI': '10.7326/M20-6976', 'article-title': 'The proportion of SARS-CoV-2 infections that are asymptomatic: a ' 'systematic review', 'volume': '174', 'year': '2021', 'journal-title': 'Ann Intern Med'}, { 'key': '2022052309232260000_2022.05.17.22275027v1.2', 'doi-asserted-by': 'crossref', 'first-page': 'e1003', 'DOI': '10.1016/S2214-109X(20)30264-3', 'article-title': 'Global, regional, and national estimates of the population at increased ' 'risk of severe COVID-19 due to underlying health conditions in 2020: a ' 'modelling study', 'volume': '8', 'year': '2020', 'journal-title': 'Lancet Glob Health'}, { 'key': '2022052309232260000_2022.05.17.22275027v1.3', 'doi-asserted-by': 'publisher', 'DOI': '10.2807/1560-7917.ES.2020.25.32.2001483'}, { 'key': '2022052309232260000_2022.05.17.22275027v1.4', 'doi-asserted-by': 'crossref', 'first-page': '886', 'DOI': '10.1016/j.cmi.2021.02.014', 'article-title': 'Prolonged SARS-CoV-2 cell culture replication in respiratory samples ' 'from patients with severe COVID-19', 'volume': '27', 'year': '2021', 'journal-title': 'Clin Microbiol Infect'}, { 'key': '2022052309232260000_2022.05.17.22275027v1.5', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41467-020-20568-4'}, { 'key': '2022052309232260000_2022.05.17.22275027v1.6', 'doi-asserted-by': 'crossref', 'first-page': '1059', 'DOI': '10.15585/mmwr.mm7031e2', 'article-title': 'Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine ' 'breakthrough infections, associated with large public gatherings - 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