Study of Obeldesivir in Nonhospitalized Participants With COVID-19 (OAKTREE)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-5245 for the Treatment of COVID-19 in Nonhospitalized Participants

The goal of this clinical study is to test if obeldesivir (GS-5245) is safe and effective for the treatment of coronavirus disease 2019 (COVID-19) in participants who have a standard risk of developing severe illness. This study will also measure how much obeldesivir gets into the blood and how long it takes for the body to get rid of it.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Obeldesivir; Drug: Obeldesivir Placebo

• Study Type: Interventional
• Enrollment (Actual): 2011
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kawasaki-Shi, Japan, 216-0006
    • Kanagawa Himawari Clinic
  • Musashino, Japan, 180-0022
    • Medical corporation Shirayurikai Swing Nozaki Clinic
  • Sapporo-Shi Toyohira-Ku, Japan, 062-0034
    • Nishioka Hospital
  • Shibuya-ku, Japan, 150-0013
    • Sato Clinic
  • Shinagawa-Ku, Japan, 140-8522
    • Tokyo Shinagawa Hospital Social Medical Corporation Association Tokyokyojuno-kai
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Emvenio Research
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Institute for Liver Health dba Arizona Clinical Trials
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health DBA Arizona Liver Health
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, MD
    • Banning, California, United States, 92220
      • Velocity Clinical Research, Banning (IP Delivery and Administering Location)
    • Colton, California, United States, 92324
      • Benchmark Research
    • Fullerton, California, United States, 92835
      • Ascada Research
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research
    • La Palma, California, United States, 90623
      • IMAX Clinical Trials, LLC
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Los Angeles, California, United States, 90057
      • L.A. Universal Research Center, Inc.
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • Northridge, California, United States, 91325
      • Valley Clinical Trials
    • Oxnard, California, United States, 93030
      • Fomat Medical Research
    • Redding, California, United States, 96001
      • Paradigm Clinical Research
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital
    • Santa Clarita, California, United States, 91351
      • Clearview Medical Research, LLC
    • Santa Monica, California, United States, 90404
      • Emvenio Research
    • Toluca Lake, California, United States, 91602
      • Med Partners, Inc. dba Premiere Medical Center of Burbank, Inc.
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Boynton Beach, Florida, United States, 33436
      • Encore Medical Research of Boynton Beach LLC
    • Brandon, Florida, United States, 33511
      • Palm Harbor Dermatology d/b/a TrueBlue Clinical Research
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc
    • Coral Gables, Florida, United States, 33134
      • Prestige Clinical Research Center Inc
    • Cutler Bay, Florida, United States, 33157
      • Beautiful Minds Clinical Research Center
    • Doral, Florida, United States, 33122
      • Vital Care Research
    • Doral, Florida, United States, 33126
      • UHC Research, LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Proactive Clinical Research,LLC
    • Hialeah, Florida, United States, 33012
      • AGA Clinical Trials
    • Hialeah, Florida, United States, 33016
      • Doral Medical Research
    • Hialeah, Florida, United States, 33016
      • Best Quality Research, Inc.
    • Hialeah, Florida, United States, 33010
      • Qway Research LLC
    • Hialeah, Florida, United States, 33013
      • Research in Miami
    • Hialeah, Florida, United States, 33016
      • 3Sync, LLC
    • Hialeah Gardens, Florida, United States, 33016
      • Evolution Clinical Trials, Inc
    • Hollywood, Florida, United States, 33024
      • Innovative Health
    • Hollywood, Florida, United States, 33201
      • Encore Medical Research, LLC
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute, LLC
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami, Florida, United States, 33135
      • Global Health Clinical Trials Corp
    • Miami, Florida, United States, 33176
      • Entrust Clinical Research
    • Miami, Florida, United States, 33144
      • Nuren Medical & Research Center
    • Miami, Florida, United States, 33155
      • Florida International Medical Research
    • Miami, Florida, United States, 33144
      • Continental Clinical Research
    • Miami, Florida, United States, 33144
      • Clinical Trial Services, Corp
    • Miami, Florida, United States, 33155
      • Bioclinical Research Alliance Inc.
    • Miami, Florida, United States, 33175
      • ProLive Medical Research, Corp
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group, LLC
    • Miami, Florida, United States, 33122
      • Advance Clinical Research Group
    • Miami, Florida, United States, 33125
      • Med-Care Research, Corp
    • Miami, Florida, United States, 33125
      • Southern Clinical Research LLC
    • Miami, Florida, United States, 33126
      • Universal Medical and Research Center, LLC.
    • Miami, Florida, United States, 33135
      • Retreat Medical Research
    • Miami, Florida, United States, 33135
      • Verus Clinical Research, Corp
    • Miami, Florida, United States, 33144
      • Dynamic Medical Research, LLC
    • Miami, Florida, United States, 33155
      • Advanced Care and Clinical Trials, LLC
    • Miami, Florida, United States, 33155
      • Cordova Research Institute, Inc
    • Miami, Florida, United States, 33155
      • D&H National Research Centers, Inc
    • Miami, Florida, United States, 33166
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33175
      • Diverse Clinical Research, LLC
    • Miami, Florida, United States, 33175
      • P&S Research, LLC.
    • Miami, Florida, United States, 33176
      • Links Clinical Trials LLC
    • Miami, Florida, United States, 33176
      • Reed Medical Research Corp
    • Miami, Florida, United States, 33180
      • MedBio Trials LLC
    • Miami, Florida, United States, 33186
      • Clinical Site Partners, LLC dba Flourish Research
    • Miami, Florida, United States, 33186
      • Phoenix Research Center, LLC
    • Miami Lakes, Florida, United States, 33014
      • Palm Springs Community Health Center
    • Miami Lakes, Florida, United States, 33014
      • Essential Clinical Research
    • Miami Lakes, Florida, United States, 33016
      • Angels Clinical Research Institute
    • Miami Lakes, Florida, United States, 33016
      • Quality Research of South Florida
    • North Miami Beach, Florida, United States, 33169
      • Oceanic Research Group
    • Palm Springs, Florida, United States, 33406
      • Castillo Torres, MD PA
    • Pembroke Pines, Florida, United States, 33026
      • Family Clinical Trials, LLC
    • South Miami, Florida, United States, 33143
      • USPA Advance Concept Medical Research Group, LLC
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
    • Tampa, Florida, United States, 33615
      • Santos Research Center, CORP
    • Tampa, Florida, United States, 33614
      • Precision Research Center
    • Tampa, Florida, United States, 33614
      • Angels Clinical Research Institute
    • Weston, Florida, United States, 33331
      • Encore Medical Reseach of Weston, LLC
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners, LLC dba Flourish Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials, LLC
    • Atlanta, Georgia, United States, 30315
      • Emvenio Research
    • East Point, Georgia, United States, 30344
      • Covenant Pulmonary Critical Care Research Institute
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • New York
    • Bronx, New York, United States, 10456
      • Prime Global Research Inc
  • North Carolina
    • Denver, North Carolina, United States, 28037
      • Shelby Clinical Research, LLC
    • Greenville, North Carolina, United States, 27834
      • The Brody School of Medicine at East Carolina University
    • Shelby, North Carolina, United States, 28150
      • Carolina Research Center, Inc.
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research, LLC
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Clinovacare Medical Research Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • St Hope Foundation, Inc.
    • Brownsville, Texas, United States, 78520
      • PanAmerican Clinical Research
    • Denison, Texas, United States, 75020
      • Premier Pulmonary Critical Care and Sleep Medicine
    • Fort Worth, Texas, United States, 26134
      • Emvenio Research
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, INC.
    • Houston, Texas, United States, 77022
      • HDH Research Inc.
    • Laredo, Texas, United States, 78041
      • Milton Haber, MD
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research, LLC
    • Plano, Texas, United States, 75024
      • Village Health Partners
    • Plano, Texas, United States, 75093
      • North Texas Family Medicine
    • Plano, Texas, United States, 75025
      • Village Health Partners
    • Red Oak, Texas, United States, 75154
      • Epic Medical Research, LLC
    • San Antonio, Texas, United States, 78229
      • STAAMP Research LLC
    • Webster, Texas, United States, 77598
      • Tranquil Clinical Research
  • Utah
    • Bountiful, Utah, United States, 84010
      • Bountiful Internal Medicine
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • West Virginia
    • Kingwood, West Virginia, United States, 26537
      • Frontier Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed, ≤ 3 days before randomization, by polymerase chain reaction (PCR), rapid antigen test, or an approved alternative assay. Serologic tests will not be accepted.
• Willing and able to complete the coronavirus disease 19 (COVID-19) symptom questionnaire prior to first dose and daily throughout the study period.

• Initial onset of COVID-19 signs/symptoms ≤ 3 days before randomization with ≥ 2 of the following targeted symptoms, at moderate or higher severity, present at randomization.

  • Stuffy or runny nose.
  • Sore throat.
  • Shortness of breath (difficulty breathing).
  • Cough.
  • Low energy or tiredness.
  • Muscle or body aches.
  • Headache.
  • Chills or shivering.
  • Feeling hot or feverish.
• Not currently hospitalized or requiring hospitalization.

Key Exclusion Criteria:

• Any risk factors for progression to severe disease.
• Planning to receive a direct acting antiviral or monoclonal antibody against SARS-CoV-2 for the treatment of COVID-19.
• Received any direct acting antiviral drug or monoclonal antibody against SARS-CoV-2 for the treatment of COVID-19 < 28 days or < 5 half-lives, whichever is longer, before randomization.
• Received any convalescent COVID-19 plasma or other antibody-based anti-SARS-CoV-2 prophylaxis at any time prior to study entry.
• Received an COVID-19 vaccine (including booster dose) < 120 days before randomization.
• Self-reported COVID-19 diagnosis < 120 days before randomization.
• Anticipated need for hospitalization < 48 hours after randomization.
• New oxygen requirement < 24 hours before randomization.
• Known influenza, or any other suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study drug.
• Known history of chronic liver disease, limited to cirrhosis, nonalcoholic steatohepatitis, alcoholic liver disease, and autoimmune hepatitis.
• Undergoing dialysis, or known history of chronic kidney disease.
• Persistent symptoms from previous COVID-19 illness that may interfere with the evaluation of response to the study drug.
• Pregnant or breastfeeding.
• Unwilling to use protocol-mandated contraception.
• Any other factor, including inability to complete the patient-reported outcome (PRO) questionnaire for the primary endpoint, making the individual, in the opinion of the investigator, unsuitable to participate in the study.
• Concurrent participation/enrollment in a separate therapeutic clinical study.

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: Obeldesivir; Participants will receive obeldesivir 350 mg twice daily for 5 days.	Drug: Obeldesivir; Tablet administered orally without regard to food.; Other Names: GS-5245
Placebo Comparator: Obeldesivir Placebo; Participants will receive obeldesivir placebo twice daily for 5 days.	Drug: Obeldesivir Placebo; Tablet administered orally without regard to food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Coronavirus Disease 2019 (COVID-19) Symptom Alleviation by Day 29	The time to alleviation of targeted COVID-19 symptoms by Day 29 for participants with symptom alleviation, was calculated as symptom alleviation date/time minus first dose date/time. For participants who completed Day 29 of the study or discontinued from the study before Day 29 without symptom alleviation (censored) and without inter-current events, time was calculated as last date/time on which symptom alleviation was assessed minus the first dose date/time or Day 28, whichever occurred first. Symptom alleviation was defined as, all targeted symptoms scored moderate or severe at baseline were scored as mild/none and all targeted symptoms scored mild/none at baseline were scored as none, for at least 48 consecutive hours. Targeted symptoms included: stuffy or runny nose, sore throat, shortness of breath, cough, low energy or tiredness, muscle or body aches, headache, chills or shivering and feeling hot or feverish. Kaplan-Meier (KM) estimates were used in outcome measure analysis.	First dose date up to Day 29
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	TEAEs were defined as 1 or both of the following: 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.; Any AEs leading to premature discontinuation of study drug. Percentages were rounded off.	First dose date up to Day 5 plus 30 days
Percentage of Participants Experiencing Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. Percentages were rounded off.	First dose date up to Day 5 plus 30 days
Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation	Percentages were rounded off.	First dose date up to Day 5 plus 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to COVID-19 Symptom Resolution by Day 29	COVID-19 symptom resolution was defined as all targeted symptoms scored as none for at least 48 consecutive hours. The first day of the 48 consecutive hours was considered the date of symptom resolution. The time to COVID-19 symptom resolution was the time (expressed as days) from the first dose date/time to the date/time of symptom resolution. KM estimates were used in the outcome measure analysis.	Day 1 up to 29
Percentage of Participants With Moderate Relapse of COVID-19 Symptoms by Day 29	COVID-19 moderate symptom relapse was defined as having at least 1 symptom being moderate or severe OR at least 2 mild symptoms OR a hospitalization for COVID-19 or death, observed on a day during COVID-19 symptom relapse. Percentages were rounded off.	Up to Day 29
Percentage of Participants With COVID-19 Related Medically Attended Visits (MAVs) or All-cause Death by Day 29	Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified. KM estimates were used in the outcome measure analysis. Percentages were rounded off.	Up to Day 29
Percentage of Participants With COVID-19 Related Hospitalization or All-cause Death by Day 29	COVID-19-related hospitalization was defined as ≥ 24 hours of acute care for a reason related to COVID-19, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This included specialized acute medical care units within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution. The date and duration (if there was 1 day difference between the start date and end date) of hospital admission, and primary reason for hospitalization (including if the hospitalization was related to COVID-19) was to be recorded. Percentages were rounded off.	Up to Day 29
Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5		Day 5
Time to Antigen Negativity	Time to antigen negativity was defined (in days) as the number of days to the first date of 2 consecutive dates achieving a negative result. Antigen negativity was defined as 2 consecutive negative SARS-CoV-2 rapid antigen test (regardless if there was missing data in between), or negative test at last available sample for participants who completed or discontinued from the study after at least 1 positive antigen test.	Day 1 up to Day 29
Percentage of Participants With Viral Antigen Rebound	Viral antigen rebound was defined as any positive SARS-CoV-2 rapid antigen test after antigen negativity. Percentages were rounded off.	Up to Day 29
Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir)		Day 1, 0.75 hour and 2 hours; Day 3, Predose and 0.75 hour; Day 5, Predose and 0.75 hour
Pharmacokinetic (PK) Parameter: AUCtau,Steady-State of GS-441524	AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady-state.	Day 5
PK Parameter: Ctau of GS-441524	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Day 1 and Day 5
PK Parameter: Cmax of GS-441524	Cmax is defined as the maximum observed plasma concentration of drug.	Day 1 and Day 5
Percentage of Participants With Relapse of COVID-19 Symptoms by Day 29	Symptom relapse means at least 2 consecutive diary entries (regardless of missing data in between) where there was any symptom (regardless of severity) OR a hospitalization for COVID-19 or a death after short symptom recovery. Percentages were rounded off.	Up to Day 29

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2023
• Primary Completion (Actual): November 28, 2023
• Study Completion (Actual): January 23, 2024

Study Registration Dates

• First Submitted: February 3, 2023
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: GS-US-611-6549; jRCT2031230285 (Other Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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