strategies and treatments for respiratory infections & viral emergencies (strive): shionogi protease inhibitor (ensitrelvir)

Conditions: COVID-19

Summary: treatments are needed to improve outcomes among patients hospitalized for covid-19, including direct-acting antiviral (daa) agents to mitigate the pathology driven by ongoing viral replication. this trial will evaluate s-217622 (ensitrelvir), an anti-sars-cov2 3c-like protease inhibitor (pi) developed by shionogi \&; co. ltd. the study design is a randomized, placebo-controlled, multi-center international clinical trial that will evaluate the clinical efficacy of ensitrelvir when given in addition to standard of care (soc) for inpatients with covid-19. the soc will be determined by local established guidelines and may include additional daa (e.g., remdesivir) and immunomodulatory treatment strategies. certain soc treatments will be pre-specified prior to randomization.


Eligibility criteria:
inclusion criteria: * age ≥18 years. * informed consent for trial participation. * hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection. * confirmation of sars-cov2 infection by nucleic acid test (nat) or equivalent non- nat test \[list of approved tests is in the pim\] collected within the prior 14 days. * onset of symptoms attributable to sars-cov2 infection occurred within 14 days before randomization. * hospitalized for the management of covid-19, with signs and/or symptoms suggestive of lower respiratory tract infection. exclusion criteria: * the patient is expected to be discharged from the hospital within the next 24 hours. * medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization. * use of a strong cyp3a inducer within 14 days prior to enrollment * moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization. * patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life. * expected inability or unwillingness to participate in study procedures. * in the opinion of the investigator, participation in a trial is not in the best interest of the patient. * allergy to investigational agent or vehicle * use of a concomitant medication that is contraindicated due to a drug-drug interaction with s-217622 * moderate to severe hepatic impairment (i.e., child-pugh class b or c) or acute liver failure. * known estimated glomerular filtration rate (egrf) \&lt;30 ml/min/1.73m 2 * continuous renal replacement therapy or chronic dialysis * current pregnancy * current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent. * women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent. * men who are unwilling to abstain from sexual intercourse with women of child- bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent. * inability to take investigational agent in tablet form by mouth.