Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019 (COVID-19): The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study
Hiroshi Mukae, Hiroshi Yotsuyanagi, Norio Ohmagari, Yohei Doi, Hiroki Sakaguchi, Takuhiro Sonoyama, Genki Ichihashi, Takao Sanaki, Keiko Baba, Yuko Tsuge, Takeki Uehara
Clinical Infectious Diseases, doi:10.1093/cid/ciac933
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 Omicron epidemic.
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>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 Omicron epidemic.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>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\u2005hours in the total score of predefined 12 COVID-19 symptoms. Safety '
'was assessed through adverse events.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>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\u2009&lt;\u20090.0001 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\u2005hours was significantly greater with ensitrelvir versus placebo in '
'several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse '
'events were mild in severity.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>Ensitrelvir treatment demonstrated a favorable antiviral efficacy '
'and potential clinical benefit with an acceptable safety profile.</jats:p>\n'
' </jats:sec>',
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