Ensitrelvir COVID-19 post-exposure prophylaxis in household contacts

Abstract

Background: Ensitrelvir, an oral severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3C-like protease inhibitor, is approved in Japan for mild-to-moderate coronavirus disease-2019 (COVID-19) treatment. No antivirals are approved for post-exposure prophylaxis in household contacts (HHCs) of index patients (IPs) with COVID-19.

Methods: this double-blind, placebo-controlled trial randomized 1:1 HHCs with negative local SARS-CoV-2 test, to ensitrelvir (day 1: 375 mg, days 2–5: 125 mg) or placebo within 72 hours of symptom onset in COVID-19–positive IPs. The primary endpoint was the proportion of HHCs in the modified intention-to-treat (mITT) population who developed COVID-19 (central laboratory–confirmed positive reverse transcriptase–polymerase chain reaction and ≥1 of 14 prespecified COVID-19 symptoms lasting for ≥48 hours) by day 10.

Results: in the mITT population (ensitrelvir: n=1,030; placebo: n=1,011), mean age was 42.4 years, 71.1% were randomized <48 hours of IP symptom onset, and 37.0% had ≥1 risk factor for severe COVID-19. The proportion of HHCs developing COVID-19 was lower with ensitrelvir (2.9%) than placebo (9.0%; risk ratio 0.33; 95% confidence interval [CI]: 0.22, 0.49). In those with risk factors, the proportion was lower with ensitrelvir (2.4%) than placebo (9.9%; risk ratio: 0.24; 95% CI: 0.12, 0.49). The proportions with treatment emergent adverse events (TEAEs; 15.1% vs 15.5%, respectively) and serious TEAEs (0.2% each) were similar; no COVID-19–related hospitalizations or fatalities were reported.

Conclusions: Ensitrelvir administration to HHCs within 72 hours of symptom onset in IPs was effective in preventing COVID-19.

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Identifiers

ORCID for Tristan W. Clark: orcid.org/0000-0001-6026-5295

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