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

Study Overview
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Brief Summary
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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, 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 S-217622 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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Shionogi Protease Inhibitor (S-217622)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-217622 plus standard of care (SOC)<br>Study investigational agent (S-217622) will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4. | Drug: Shionogi Protease Inhibitor (S-217622)<br>* S-217622 is an oral anti-SARS-CoV2 PI that does not require ritonavir co-administration The dose is 375/125 (375 mg on Day 0, followed by 125 mg daily on Days 1-4).<br>|
| Placebo Comparator: placebo plus standard of care (SOC)<br>Study investigational placebo (S-217622) will be administered as oral tablets with dosing of 375mg (3 tabs) once on Day 0 and 125mg (1 tab) once daily on Days 1-4. All participants will receive the full 5-day course, including those who are discharged from hospitalization prior to Day 4. | Drug: placebo<br>* Placebo is an oral tablet administered once (3 tabs) on Day 0 and once (1 tab) daily on days 1-4, 5-day course.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to Recovery Scale assessed over 60 days (DRS-60) | DRS-60 is a version of the STRIVE clinical recovery scale (CRS) which combines time to recovery with non-recovered clinical state and death to an ordinal outcome.0 indicates best results, 60 represents recovered on Day 60, with not recovered by Day 60 coded as 61 and death (worst outcome) as 62. | 60 days post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | proportion of participants who died by Day 60 | 60 days post-treatment | 
| a 3-category ordinal outcome | the following categories: recovered (alive and at home at Day 60), alive and not recovered, and dead | 60 days post-treatment | 
| time to recovery |  | 60 days post-treatment | 
| proportion of participants who died or required new invasive mechanical ventilation |  | 60 days post-treatment |