Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor (Ensitrelvir)

Inclusion Criteria:

• Age ≥18 years.

• Informed consent for trial participation.

• Hospital admission (or boarding in an emergency department or other area awaitinghospital 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 beforerandomization.

• Hospitalized for the management of COVID-19, with signs and/or symptoms suggestiveof 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 itsmanifestations) 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 andlife 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 bestinterest of the patient.

• Allergy to investigational agent or vehicle

• Use of a concomitant medication that is contraindicated due to a drug-druginteraction with S-217622

• Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liverfailure.

• Known estimated glomerular filtration rate (eGRF) <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 thelast dose of investigational agent.

• Women of child-bearing potential who are unwilling to abstain from sexualintercourse with men or practice appropriate contraception through 30 days from thelast 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 doseof the investigational agent.

• Inability to take investigational agent in tablet form by mouth.