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

• ClinicalTrials.gov Identifier: NCT05605093
• Recruitment Status: Recruiting
• First Posted: November 4, 2022
• Last Update Posted: May 26, 2023
• Sponsor: University of Minnesota
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): University of Minnesota

Tracking Information

• First Submitted Date: October 28, 2022
• First Posted Date: November 4, 2022
• Last Update Posted Date: May 26, 2023
• Actual Study Start Date: December 23, 2022
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 28, 2022)

Days to Recovery Scale assessed over 60 days (DRS-60) [ Time Frame: 60 days post-intervention ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 28, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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, 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Shionogi Protease Inhibitor (S-217622)
  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).
• Drug: placebo
  Placebo is an oral tablet administered once (3 tabs) on Day 0 and once (1 tab) daily on days 1-4, 5-day course.

Study Arms

• Experimental: S-217622 plus standard of care (SOC)
  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.
  Intervention: Drug: Shionogi Protease Inhibitor (S-217622)
• Placebo Comparator: placebo plus standard of care (SOC)
  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.
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 28, 2022): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

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) <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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: James Neaton, PhD; 612-626-9040; neato001@umn.edu

• Listed Location Countries: Japan, Singapore, Ukraine, United States

Administrative Information

• NCT Number: NCT05605093
• Other Study ID Numbers: S-217622
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Minnesota
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Minnesota
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Jens Lundgren, PhD; University of Copenhagen
• Study Chair: James Neaton, PhD; University of Minnesota

• PRS Account: University of Minnesota
• Verification Date: May 2023