Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting

A Phase 3 Randomized, Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of COVID-19 in an Outpatient Setting

The primary objectives of this study are to evaluate the efficacy of remdesivir (RDV) in reducing the rate of of coronavirus disease 2019 (COVID-19) related hospitalization or all-cause death in non-hospitalized participants with early stage COVID-19 and to evaluate the safety of RDV administered in an outpatient setting.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: RDV; Drug: Placebo to Match RDV

• Study Type: Interventional
• Enrollment (Actual): 584
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, DK9000
    • Aalborg University Hospital
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
  • Odense, Denmark, DK5000
    • Odense University Hospital
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clinic
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospitals NHS Foundation Trust
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital
  • London, United Kingdom, NW1 6BN
    • University College Hospital
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Newcastle upon Tyne Hospitals NHS Foundation Trust
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • Arizona Clinical Trials
  • California
    • Eureka, California, United States, 95501
      • St Joseph Hospital Eureka
    • Fullerton, California, United States, 92385
      • St. Joseph Heritage Healthcare
    • Huntington Beach, California, United States, 92648
      • Elevated Health
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group
    • Los Angeles, California, United States, 90057
      • LA Universal Center, INC.
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Oakland, California, United States, 94611
      • Kaiser Permanente Northern California
    • Oxnard, California, United States, 93030
      • Fomat Medical Research
    • Sacramento, California, United States, 95817
      • UC Davis Health
    • Sacramento, California, United States, 95823
      • Kaiser Permanente Northern California, 6600 Bruceville Road
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Northern California, 2025 Morse Ave
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
    • San Francisco, California, United States, 94080
      • Kaiser Permanente Northern California, 1200 El Camino Real
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Northern California, 2425 Geary Blvd
    • San Jose, California, United States, 95119
      • Kaiser Permanente Northern California, 250 Hospital Parkway, Suite 850
    • San Leandro, California, United States, 94577
      • Kaiser Permanente Northern California, 2500 Merced St
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
    • Toluca Lake, California, United States, 91602
      • Premiere Medical Center of Burbank, Inc
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Northern California, 975 Sereno Drive
    • Whittier, California, United States, 90603
      • New Hope Research Development DBA HCD
  • Colorado
    • Denver, Colorado, United States, 80210
      • Centura Health Porter Place
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Nuvance Health
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • RecioMed Clinical Research Network
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Invesclinic
    • Fort Pierce, Florida, United States, 34982
      • Lawnwood Regional Medical Center
    • Hialeah Gardens, Florida, United States, 33016
      • Evolution Clinical Trials
    • Hollywood, Florida, United States, 33201
      • Encore Medical Research
    • Loxahatchee Groves, Florida, United States, 33470
      • Advanced Pulmonary Research Institute
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute
    • Miami, Florida, United States, 33144
      • Laguna Clinical Research Associates
    • Palm Springs, Florida, United States, 33406
      • CTMD Research, Inc
    • Palmetto Bay, Florida, United States, 33157
      • IMIC Inc
    • Pembroke Pines, Florida, United States, 33029
      • Luminous Clinical Research - South Florida Urgent Care
    • Tampa, Florida, United States, 33614
      • St. Josephs Comprehensive Research Institute
    • Vero Beach, Florida, United States, 32960
      • AIDS Research and Treatment Center of the Treasure Coast
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute PA
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials
    • Macon, Georgia, United States, 31210
      • Mercer University School of Medicine
  • Illinois
    • Burr Ridge, Illinois, United States, 60527
      • Infectious Disease Associates of Kansas City, P.C.Infectious Disease Associates of Kansas City, P.C.
    • Burr Ridge, Illinois, United States, 60527
      • Metro Infectious Disease Consultants
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Baltimore
    • Baltimore, Maryland, United States, 21201
      • Holy Cross Hospital, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • South Weymouth, Massachusetts, United States, 02190
      • South Shore Hospital
    • West Roxbury, Massachusetts, United States, 02132
      • VA Boston Healthcare System
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Flint, Michigan, United States, 48532
      • Onyx Research Institute
  • Mississippi
    • Gulfport, Mississippi, United States, 39501
      • Memorial Hospital of Gulfport
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Metro Infectious Disease Consultants
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AB Clinical Trials
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Axces Research Group
  • New York
    • Flushing, New York, United States, 11355
      • New York Presbyterian Hospital
    • New Hyde Park, New York, United States, 11040
      • Northwell Health
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Atrium Health Carolinas Medical Center
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital
  • Oklahoma
    • Tahlequah, Oklahoma, United States, 74464
      • Cherokee Nation WW Hastings Hospital
  • Oregon
    • Portland, Oregon, United States, 92775
      • Providence St. Vincent Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Avera Research Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Health Science Center
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Bellaire, Texas, United States, 77401
      • UT Physicians
    • College Station, Texas, United States, 77845
      • Baylor University Medical Center, 700 Scott and White Dr.
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Forney, Texas, United States, 75126
      • Care United Research, LLC
    • Harlingen, Texas, United States, 78550
      • VIP Trials
    • Houston, Texas, United States, 77030
      • University of Texas
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, INC
    • Irving, Texas, United States, 75061
      • Baylor University Medical Center, 1901 North McArthur Blvd
    • Laredo, Texas, United States, 78041
      • Laguna Clinical Research Associates
    • Longview, Texas, United States, 75605
      • Diagnostic Clinic of Longview - Center for Clinical Research
    • San Antonio, Texas, United States, 78229
      • STAAMP Research
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice
    • Waco, Texas, United States, 76708
      • Baylor University Medical Center, 2201 MacArthur Dr., Suite 100
    • Waxahachie, Texas, United States, 75165
      • ClinPoint Trials
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Healthcare
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Virginia Commonwealth University
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Center Everett
    • Port Orchard, Washington, United States, 98366
      • Sound Medical Research
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Wisconsin Corporation for Biomedical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Willing and able to provide written informed consent, (individuals ≥ 18 years of age) or assent (individuals ≥ 12 and < 18 years of age) prior to performing study procedures. Individuals age ≥ 18 years may be enrolled with the consent of a legal representative where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC). For individuals ≥ 12 and < 18 years of age, a parent or legal guardian must be willing and able to provide written informed consent prior to performing study procedures

• Either:

  • Age ≥ 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 IRB or IEC with at least 1 pre-existing risk factor for progression to hospitalization (chronic lung disease, hypertension, cardiovascular or cerebrovascular disease, diabetes, obesity (body mass index ≥ 30), immunocompromised, chronic mild or moderate kidney disease, chronic liver disease, current cancer, or sickle cell disease)
  • Or aged ≥ 60 years
• Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection confirmed by molecular diagnosis (nucleic acid (polymerase chain reaction (PCR) or antigen testing) ≤ 4 days prior to screening
• Presence of ≥ 1 symptom(s) consistent with COVID-19 for ≤ 7 days prior to randomization
• Not currently requiring hospitalization (hospitalization defined as ≥ 24 hours of acute care)

Key Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment and prevention for COVID-19
• Prior hospitalization for COVID-19
• Treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 or administration of any SARS-CoV-2 (or COVID-19) vaccine
• Requiring oxygen supplementation

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remdesivir (RDV); Participants will receive a single dose of intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.	Drug: RDV; Administered as an intravenous infusion; Other Names: Veklury®; GS-5734™
Placebo Comparator: Placebo; Participants will receive IV placebo to match (PTM) RDV on Days 1 to 3.	Drug: Placebo to Match RDV; Administered as an intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization (Defined as at Least 24 Hours of Acute Care) or All-Cause Death by Day 28	The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.	Randomization up to Day 28
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.	First dose date up to last dose date (maximum: 3 days) plus 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With COVID-19 Related Medical Visits Attended in Person by the Participant and a Health Care Professional (MAVs) or All-Cause Death by Day 28	The composite outcome of COVID-19 related MAVs or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.	Randomization up to Day 28
Percentage of Participants Who Died by Day 28		Randomization up to Day 28
Percentage of Participants With COVID-19 Related Hospitalization at Day 28	COVID-19 related hospitalization is defined as at least 24 hours of acute care derived by COVID-19 related hospitalization reported by the site. The percentage of the outcome and the corresponding 95% confidence interval were from Kaplan-Meier estimate.	Randomization up to Day 28
Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14	The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.	Randomization up to Day 14
Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14	The composite outcome of COVID-19 related MAVs or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.	Randomization up to Day 14
Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7	The time-weighted average change from baseline to study Day 7 (DAVG7) in SARS-CoV-2 viral load is defined as the time-weighted average between the first postbaseline value through the last available value up to Day 7 minus the baseline value in SARS-CoV-2 viral load (log10 copies/mL). DAVG7 is calculated using the trapezoidal rule and the area under the curve (AUC). For participants with data through days prior to Day 7, the time-weighted average change used data up to last available timepoint. If there was no postbaseline data, the participant was excluded from the analysis.	Baseline up to Day 7
Time to Alleviation (Mild or Absent) of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted Influenza Patient-Reported Outcome Plus Questionnaire (FLU-PRO Plus)	The COVID-19-adapted FLU-PRO Plus is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild). Time to alleviation of baseline COVID-19 symptoms is defined (in days) as: First Date of the two consecutive dates achieving alleviation - First dose Date + 1. If a participant had not achieved symptom alleviation at last FLU-PRO Plus assessment or early discontinuation of study, the participant was censored at last FLU-PRO Plus assessment date.	First Dose Date up to Day 14
Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire	The worsening after alleviation of baseline COVID-19 symptoms is defined as for a participant who has achieved alleviation of baseline COVID-19 symptoms, if symptom scored as 2 or higher at baseline is scored as 2 or higher postbaseline after achieved alleviation, or symptoms scored as 1 at baseline are scored as 1 or higher postbaseline after achieved alleviation. The COVID-19-adapted FLU-PRO Plus was used. It is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild).	First dose date up to Day 28
Percentage of Participants Who Required Oxygen Supplementation by Day 28		Randomization up to Day 28

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Actual): May 6, 2021
• Study Completion (Actual): May 6, 2021

Study Registration Dates

• First Submitted: August 5, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Remdesivir
• Other Study ID Numbers: GS-US-540-9012; 2020-003510-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No