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 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) <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.