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

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.