Clinical trial NCT04292899: Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe Coronavirus Disease (COVID-19)
Official title: A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-03-03
Enrollment: 4891
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.


Eligibility criteria: Key Inclusion Criteria:

* Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (age ≥ 18), or willing and able to provide assent (age ≥ 12 to \< 18, where locally and nationally approved) prior to performing study procedures
* Aged ≥ 18 years (at all sites), or aged ≥ 12 and \< 18 years of age weighing ≥ 40 kg (where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC))
* Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization
* Currently hospitalized
* Peripheral capillary oxygen saturation (SpO2) ≤ 94% or requiring supplemental oxygen at screening

Key Exclusion Criteria:

* Participation in any other clinical trial of an experimental treatment for COVID-19
* Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited \< 24 hours prior to study drug dosing
* Evidence of multiorgan failure
* Mechanically ventilated \[including veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)\] ≥ 5 days, or any duration of veno-arterial (V-A) ECMO.
* Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN)
* Creatinine clearance \< 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976} and Schwartz Formula for participants \< 18 years of age

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 14
timeFrame: Day 14
Secondary outcomes:
measure: Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to last dose date (maximum: 10 days) plus 30 days
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 3340 E. La Palma Avenue
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Burlingame
country: United States
facility: Mills-Peninsula Medical Center
state: California
city: Castro Valley
country: United States
facility: Eden Medical Center
state: California
city: Downey
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 9333 Imperial Highway
state: California
city: Fontana
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 9961 Sierra Ave
state: California
city: Fortuna
country: United States
facility: St Joseph Hospital Eureka
state: California
city: Harbor City
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 25825 S. Vermont Ave.
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 6041 Cadillac Ave.
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 5601 De Soto Avenue
state: California
city: Mission Viejo
country: United States
facility: Mission Hospital Regional Medical Center
state: California
city: Moreno Valley
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 27300 Iris Avenue
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland Medical Center
state: California
city: Ontario
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 2295 S. Vineyard Avenue
state: California
city: Orange
country: United States
facility: The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange
state: California
city: Panorama City
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 13651 Willard Street
state: California
city: Riverside
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 10800 Magnolia Avenue
state: California
city: Roseville
country: United States
facility: Sutter Medical Center Sacramento, One Medical Plaza
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 4647 Zion Avenue
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Los Angeles Medical Center, 9455 Clairemont Mesa Blvd
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Oakland Medical Center, 1200 El Camino Real
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Infectious Disease Associates Medical Group
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Oakland Medical Center, 2425 Geary Blvd
state: California
city: San Jose
country: United States
facility: Kaiser Permanente Oakland Medical Center, 250 Hospital Parkway, Suite 850
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente Oakland Medical Center, 2500 Merced St
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Oakland Medical Center, 700 Lawrence Expressway
state: California
city: Santa Monica
country: United States
facility: Providence St. Johns Medical Center
state: California
city: Santa Rosa
country: United States
facility: Sutter Santa Rosa Regional Hospital
state: California
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Denver, University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: SCL Health St. Joseph Hospital, 1375 East 19th Ave
state: Colorado
city: Denver
country: United States
facility: SCL Health St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Lafayette
country: United States
facility: SCL Health St. Joseph Hospital, 200 Exempla Circle.
state: Colorado
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Honolulu
country: United States
facility: Kaiser Permanente Hawaii Moanalua Medical Center
state: Hawaii
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital and Harvard Medical School
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: The University of Michigan Hospitals and Health Systems
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin Healthcare
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Missoula
country: United States
facility: Providence St Patrick Hospital and International Heart Institute of MT Foundation
state: Montana
city: Lebanon
country: United States
facility: Darmouth-Hitchhock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hillsborough
country: United States
facility: Robert Wood Johnson University Hospital Somerset
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital Somerset, 1 RWJ Place
state: New Jersey
city: Newark
country: United States
facility: Robert Wood Johnson University Hospital Somerset, 201 Lyons Avenue
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: James J. Peters Veterans Administration Medical Center
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: Lagrangeville
country: United States
facility: Danbury Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: North Shore University Hospital, 270-05 76th Ave
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai, 350 East 17th Street
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai, 1000 10th Avenue
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai, 440 West 114th St.
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Hillsboro
country: United States
facility: Kaiser Sunnyside Medical Center, 2875 NW Stucki Ave
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Kaiser Sunnyside Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, 51 N. 31st Street
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Richland Hospital, 701 Grove Road
state: South Carolina
city: Dallas
country: United States
facility: The Liver Institute of Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center Amelia Court, HIV Research Clinic
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center Amelia Court, HIV Research Clinic, 5201 Harry Hines Blvd.
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center Amelia Court, HIV Research Clinic, 6201 Harry Hines Blvd
state: Texas
city: Fort Worth
country: United States
facility: Baylor University Medical Center, 1400 8th Ave
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Temple
country: United States
facility: Baylor University Medical Center, 2401 S. 31st St.
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Arlington
country: United States
facility: Virginia Hospital Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Richmond
country: United States
facility: VCU Health Medical Center
state: Virginia
city: Everett
country: United States
facility: Providence Regional Medical Center Everett
state: Washington
city: Kennewick
country: United States
facility: Kadlec Regional Medical Center
state: Washington
city: Olympia
country: United States
facility: Providence St. Peter Hospital
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Center for Comprehensive Care
state: Washington
city: Spokane
country: United States
facility: MultiCare Deaconess Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Tacoma General Hospital
state: Washington
city: Tacoma
country: United States
facility: St Joseph Medical Center
state: Washington
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Montpelier Cedex 5
country: France
facility: CHU de Montpellier-Hopital Gui de Chauliac
city: Nantes
country: France
facility: CHU de Nantes-Hotel Dieu
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik Infektiologie Pneumologie
city: Düsseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf, Klinik fur Gastroenterologie, Hepatologie und Infektiologie
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH Klinik fur Infektiologie, Tropenmedizin, Nephrologie und Rheumatologie
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TU Munchen, Klinik und Poliklinik Innere Medizin 2
city: München
country: Germany
facility: Klinik für Hämatologie, Onkologie, Immunologie
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus (RBK), Klinik Schillerhohe (KSH) und Dr. Margarete Fischer-Bosch-Institut fur klinische Pharmakologie (IKP)
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Bergamo
country: Italy
facility: UOC Malattie Infettive, ASST Papa Giovanni XXIII
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Cremona
country: Italy
facility: ASST di Cremona - Azienda Socio Sanitaria Territor
city: Milano
country: Italy
facility: UOC Malattie Infettive, IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Dipartimento di Malattie Infettive, Malattie Infettive I- Malattie Infettive III, AssT Fatebenefratelli Sacco Ospedale Luigi Sacco
city: Milan
country: Italy
facility: UO Malattie Infettive, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Padova PD
country: Italy
facility: UOC Medicina Di Laboratorio, Azienda Ospedaliera di Padova
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Pavia
country: Italy
facility: UOC Malattie Infettive I, Fondazione IRCCS Policlinio San Matteo
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto AUSL di Piacenza
city: Roma
country: Italy
facility: UOC Malattie Infettive ad Alta Intensita di Cure, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
city: Torino
country: Italy
facility: Clinica Universitaria Malattie Infettive, Ospedale Amedeo di Savoia
city: Kanagawa
country: Japan
facility: Yokohama Municipal Citizen's Hospital
city: Nagoya
country: Japan
facility: Nagoya City East Medical Center
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Bokutoh Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Medical Center
city: Seoul
country: Korea, Republic of
facility: National Medical Center
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centre - Location AMC
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: National Centre for Infectious Diseases, Tan Tock Seng Hospital
city: Alcalá De Henares
country: Spain
facility: Hospital Principe de Asturias
state: Madrid
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Bizkaia
country: Spain
facility: Hospital Universitario Cruces
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital, Ostra
city: Malmo
country: Sweden
facility: SUS (Skanes University Hospital)
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Genève 14
country: Switzerland
facility: Hopitaux Universitaires de Genève
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Locarno La Carità
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: Greater London
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospital
city: London
country: United Kingdom
facility: Northwick Park Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Trust
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Pennine Acute Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Goldman JD, Lye DCB, Hui DS, Marks KM, Bruno R, Montejano R, Spinner CD, Galli M, Ahn MY, Nahass RG, Chen YS, SenGupta D, Hyland RH, Osinusi AO, Cao H, Blair C, Wei X, Gaggar A, Brainard DM, Towner WJ, Munoz J, Mullane KM, Marty FM, Tashima KT, Diaz G, Subramanian A; GS-US-540-5773 Investigators. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med. 2020 Nov 5;383(19):1827-1837. doi: 10.1056/NEJMoa2015301. Epub 2020 May 27.
citation: Jacobson KB, Rao M, Bonilla H, Subramanian A, Hack I, Madrigal M, Singh U, Jagannathan P, Grant P. Patients With Uncomplicated Coronavirus Disease 2019 (COVID-19) Have Long-Term Persistent Symptoms and Functional Impairment Similar to Patients with Severe COVID-19: A Cautionary Tale During a Global Pandemic. Clin Infect Dis. 2021 Aug 2;73(3):e826-e829. doi: 10.1093/cid/ciab103.
citation: Olender SA, Perez KK, Go AS, Balani B, Price-Haywood EG, Shah NS, Wang S, Walunas TL, Swaminathan S, Slim J, Chin B, De Wit S, Ali SM, Soriano Viladomiu A, Robinson P, Gottlieb RL, Tsang TYO, Lee IH, Hu H, Haubrich RH, Chokkalingam AP, Lin L, Zhong L, Bekele BN, Mera-Giler R, Phulpin C, Edgar H, Gallant J, Diaz-Cuervo H, Smith LE, Osinusi AO, Brainard DM, Bernardino JI; GS-US-540-5773 and GS-US-540-5807 Investigators. Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care. Clin Infect Dis. 2021 Dec 6;73(11):e4166-e4174. doi: 10.1093/cid/ciaa1041.