Clinical trial NCT05605093: Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor (Ensitrelvir)
Official title: Strategies and Treatments for Respiratory Infections & Viral Emergencies (STRIVE): Shionogi Protease Inhibitor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-11-04
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (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.

Primary outcomes:
measure: Days to Recovery Scale assessed over 60 days (DRS-60)
timeFrame: 60 days post-intervention
Secondary outcomes:
measure: mortality
timeFrame: 60 days post-treatment
measure: a 3-category ordinal outcome
timeFrame: 60 days post-treatment
measure: time to recovery
timeFrame: 60 days post-treatment
measure: proportion of participants who died or required new invasive mechanical ventilation
timeFrame: 60 days post-treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham University Hospital (Site 213-002)
state: Alabama
city: Tucson
country: United States
facility: Banner University Medical Center Tucson (Site 206-004)
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Healthcare System (Site 074-009)
state: Arizona
city: Fresno
country: United States
facility: UCSF Fresno (Site 203-005)
state: California
city: Loma Linda
country: United States
facility: VA Loma Linda Healthcare System (Site 074-017)
state: California
city: Long Beach
country: United States
facility: MemorialCare Health System (Site 066-003
state: California
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System (Site 074-026)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Site 208-002)
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (Site 203-002)
state: California
city: Mather
country: United States
facility: VA Northern California Health Care System (Site 074-023)
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian (Site 080-026)
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Palo Alto Health Care System (VAPAHCS) (Site 074-005)
state: California
city: Sacramento
country: United States
facility: UC Davis Health (Site 203-004)
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System (Site 074-016)
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital and Trauma Center (Site 213-007)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mount Zion (203-007)
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC (Site 074-002)
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (Site 203-001)
state: California
city: Stanford
country: United States
facility: Stanford University Hospital & Clinics (Site 203-003)
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation (Site 066-002)
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center (Site 074-010)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital (Site 204-001)
state: Colorado
city: Denver
country: United States
facility: Public Health Institute at Denver Health (Site 017-004)
state: Colorado
city: New Haven
country: United States
facility: Yale University (Site 025-001)
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institute/MedStar Washington Hospital Center (Site 009-021)
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Medical Center (Site 009-004)
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida - Gainesville (Site 201-004)
state: Florida
city: Miami
country: United States
facility: Miami VA Healthcare System (Site 074-003)
state: Florida
city: Orlando
country: United States
facility: Orlando VA Medical Center (Site 074-032)
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital (032-001)
state: Florida
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County (Site 080-046)
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago (Site 008-012)
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital (Site 080-049)
state: Illinois
city: Fort Wayne
country: United States
facility: Lutheran Medical Group (Site 301-010)
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Hospital (Site 080-044)
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky (Site 210-004)
state: Kentucky
city: Bethesda
country: United States
facility: NIH Clinical Center (Site 080-043)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (202-002)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Site 202-001)
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center (Site 201-001)
state: Massachusetts
city: Worcester
country: United States
facility: UMass Chan Medical School (Site 080-007)
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System (Site 074-028)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System (Site 014-001)
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital (Site 205-005)
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin Healthcare Research Institute (Site 027-001)
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center (Site 112-001)
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic (Site 054-001)
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center (Site 202-005)
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine (Site 003-001)
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center (Site 080-045)
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center (301-024)
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital (Site 019-001)
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack Meridian Health (Site 301-030)
state: New Jersey
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center (028-001)
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Hospital (Site 213-008)
state: New Mexico
city: Santa Fe
country: United States
facility: CHRISTUS - St. Vincent (Site 080-051)
state: New Mexico
city: Bronx
country: United States
facility: Lincoln Medical Center (Site 003-016)
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Hospital (Site 206-001)
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Weiler campus (Site 206-003)
state: New York
city: Bronx
country: United States
facility: James J. Peters VAMC (Site 023-003)
state: New York
city: Brooklyn
country: United States
facility: NYU Brooklyn (301-033)
state: New York
city: Flushing
country: United States
facility: New York Presbyterian Queens (003-005)
state: New York
city: Long Island City
country: United States
facility: Mount Sinai Queens (Site 081-105)
state: New York
city: Mineola
country: United States
facility: NYU Long Island (301-034)
state: New York
city: New York
country: United States
facility: New York University Tisch Hospital (Site 301-013)
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center (Site 301-012)
state: New York
city: New York
country: United States
facility: NYC Health + Hospital Harlem (Site 003-003)
state: New York
city: New York
country: United States
facility: Weill Cornell Clinical Research Unit (065-001)
state: New York
city: Potsdam
country: United States
facility: St. Lawrence Health System (Site 301-029)
state: New York
city: Durham
country: United States
facility: Duke University Hospital (Site 301-006)
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health (Site 210-001)
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center (Site 207-003)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation (Site 207-001)
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center (Site 207-004)
state: Ohio
city: Portland
country: United States
facility: Portland VA Health Care System (074-024)
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center (Site 209-002)
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital (Site 080-036)
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital (Site 080-039)
state: Rhode Island
city: Warwick
country: United States
facility: Kent County Memorial Hospital (080-048)
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center (Site 074-015)
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina (Site 210-002)
state: South Carolina
city: Rapid City
country: United States
facility: Monument Health Rapid City Hospital (Site 213-005)
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 212-001)
state: Tennessee
city: Abilene
country: United States
facility: Hendrick Medical Center (Site 080-014)
state: Texas
city: Corpus Christi
country: United States
facility: CHRISTUS Spohn Shoreline Hospital (Site 080-001)
state: Texas
city: Dallas
country: United States
facility: Baylor, Scott and White Health (301-003)
state: Texas
city: Dallas
country: United States
facility: Parkland Health and Hospital Systems (Site 084-002)
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center (Site 084-001)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital (Site 301-028)
state: Texas
city: Houston
country: United States
facility: MEDVAMC (Site 074-006)
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center (Site 203-006)
state: Texas
city: Longview
country: United States
facility: CHRISTUS Good Shepherd Medical Center (Site 080-031)
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio (Site 009-022)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center (Site 211-001)
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health (Site 211-002)
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System, University Hospital (Site 210-003)
state: Virginia
city: Salem
country: United States
facility: Salem VA Medical Center (Site 074-014)
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center (208-001)
state: Washington
city: Spokane
country: United States
facility: Providence (Sacred Heart) (Site 213-004)
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Medicine
state: West Virginia
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital (074-030)
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital (052-001)
state: Wisconsin
city: La Plata
country: Argentina
facility: Instituto Medico Platense (Site 611-025)
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Sanatorio Allende (Site 611-030)
state: Cordoba
city: Villa Regina
country: Argentina
facility: Clínica Central S.A. (611-028)
state: Rio Negro
city: Rosario
country: Argentina
facility: Sanatorio Británico S.A. (611-027)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: CEMIC (Site 611-021)
city: Cordoba
country: Argentina
facility: Hospital Rawson (Site 611-012)
city: Santa Fe
country: Argentina
facility: Sanatorio Medico de Diagnostico y Tratamiento (611-029)
city: Liverpool
country: Australia
facility: South Western Sydney Local Health District, Liverpool (Site 612-063)
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital (Site 612-002)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital (Site 612-058)
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health (612-020)
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital (Site 612-017)
state: Victoria
city: Caxias Do Sul
country: Brazil
facility: Fundação Universidade Caxias do Sul Hospital Geral (649-218)
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre (649-101)
state: RS
city: Criciuma
country: Brazil
facility: Sociedade Literária e Caritativa Santo Agostinho - Hospital São José (Site 649-204)
state: SC
city: Florianopolis
country: Brazil
facility: Hospital Nereu Ramos (Site 649-210)
state: SC
city: Joinville
country: Brazil
facility: Unimed Joinville Cooperativa de Trabalho Médico (Site 649-202)
state: SC
city: Marília
country: Brazil
facility: Associação Beneficente Hospital Universitário - Universidade de Marília (Site 649-212)
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emílio Ribas - IIER (Site 649-001)
state: SP
city: Sao Paulo
country: Brazil
facility: Real e Benemérita Associação Portuguesa de Beneficência de São Paulo (Site 649-201
state: SP
city: Sao Paulo
country: Brazil
facility: Associação Beneficente Síria - HCor (Site 649-203)
state: SP
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sirio-Libanês (Site 649-217)
state: SP
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz (649-215)
state: SP
city: São Paulo
country: Brazil
facility: Hospital SEPACO (649-207)
state: SP
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital, Skejby (625-002)
state: N
city: Aalborg
country: Denmark
facility: Aalborg Hospital (Site 625-005)
city: Copenhagen
country: Denmark
facility: Rigshospitalet, CHIP (Site 625-006)
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital (Site 625-013)
city: Hellerup
country: Denmark
facility: Herlev/Gentofte Hospital (Site 625-012)
city: Hillerød
country: Denmark
facility: Nordsjaellands Hospital, Hillerod (Site 625-009)
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital, Department of Infections Diseases (Site 625-001)
city: Kolding
country: Denmark
facility: Kolding Sygehus, Medicinsk Afdeling (Site 625-011)
city: Odense
country: Denmark
facility: Odense University Hospital (Site 625-004)
city: Roskilde
country: Denmark
facility: Zealand University Hospital Roskilde (Site 625-010)
city: Tbilisi
country: Georgia
facility: AIDS and Clinical Immunology Research Center (Site 627-201)
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Medizinische Klinik I, Immunologische Ambulanz (622-010)
city: Cologne
country: Germany
facility: Klinik I für Innere Medizin der Universität zu Köln (Site 622-008)
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe Univ. Hosp., Infektionsambulanz CRS (622-001)
city: Athens
country: Greece
facility: Dept of Critical Care and Pulmonary Medicine, Evangelismos General Hospital (635-020)
state: Attica
city: Athens
country: Greece
facility: 1st Respiratory Medicine Dept, Athens University Medical School (635-015)
state: Attica
city: Athens
country: Greece
facility: 3rd Dept of Medicine, Medical School (635-022)
state: Attica
city: Athens
country: Greece
facility: Attikon University General Hospital (Site 635-009)
state: Attica
city: Alexandroupolis
country: Greece
facility: Democritus University of Thrace (635-021)
state: Evros
city: Toyoake
country: Japan
facility: Fujita Health University Hospital (Site 612-105)
state: Aichi
city: Shinjuku-Ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine (Site 612-101)
state: Tokyo
city: Osaka
country: Japan
facility: Rinku General Medical Center (Site 612-107)
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital (Site 612-904)
state: Gyeonggi
city: Seocho
country: Korea, Republic of
facility: Seoul St. Mary's Hospital (Site 612-903)
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center (612-901)
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital (Site 612-902)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Site 653-001)
state: Cdmx
city: Mexico City
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias Ismael Cosió Villegas (Site 653-002)
state: Cdmx
city: Oaxaca City
country: Mexico
facility: Hospital General Dr. Aurelio Valdivieso (Site 653-004)
state: OA
city: Abuja
country: Nigeria
facility: Institute of Human Virology-Nigeria (IHVN) (Site 612-601)
state: FCT
city: Lima
country: Peru
facility: Hospital Nacional Hipolito Unanue (651-008)
city: Lima
country: Peru
facility: Hospital Nacional Sergio E. Bernales (651-007)
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny (Site 625-302)
city: San Juan
country: Puerto Rico
facility: VA Caribbean Health Care (074-033)
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital (Site 612-201)
city: Durban
country: South Africa
facility: Durban International Clinical Research Site (WWH) (652-005)
state: KwaZulu-Natal
city: Pietermaritzburg
country: South Africa
facility: Greys Hospital (080-202)
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: University of Cape Town (UCT) Lung Institute (Site 080-201)
state: Western Cape
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (626-003)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar (626-025)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron (Site 626-033)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (626-004)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón (Site 626-001)
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos (Site 626-017)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz (Site 626-012)
city: Zurich
country: Switzerland
facility: University Hospital Zurich (Site 621-201)
city: Bangkok
country: Thailand
facility: Chulalongkorn University and The HIV-NAT (Site 613-001)
city: Khon Kaen
country: Thailand
facility: Khon Kaen University, Srinagarind Hospital (Site 613-003)
city: Entebbe
country: Uganda
facility: MRC/UVRI & LSHTM Uganda Research Unit (634-601)
city: Gulu
country: Uganda
facility: Gulu Regional Referral Hospital (634-603)
city: Kampala
country: Uganda
facility: St. Francis Hospital, Nsambya (Site 634-607)
city: Lira
country: Uganda
facility: Lira Regional Referral Hospital (634-605)
city: Masaka
country: Uganda
facility: Masaka Regional Referral Hospital (634-606)
city: Ivano-Frankivs'k
country: Ukraine
facility: Central City Clinical Hospital of Ivano-Frankivsk City Council (Site 627-302)
city: Kyiv
country: Ukraine
facility: Treatment and Diagnostic Center ADONIS Plus (627-304)
city: Zhytomyr
country: Ukraine
facility: Hospital #1 of Zhytomyr City Council (627-303)
city: London
country: United Kingdom
facility: Royal Free Hospital (634-006)
city: London
country: United Kingdom
facility: Guy's & St. Thomas' NHS Foundation Trust (Site 634-011)
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary (Site 634-007)
city: Harare
country: Zimbabwe
facility: Parirenyatwa General Hospital (Site 634-901)
Study officials:
affiliation: University of Minnesota
name: Cavan Reilly, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Jason Baker, MD
role: STUDY_CHAIR
References: