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NCT05715528: OAKTREE

Study of Obeldesivir in Nonhospitalized Participants With COVID-19

Completed Phase 3 Results posted Last updated 24 December 2024
What this trial tests

Phase 3 trial testing Obeldesivir in COVID-19 in 2,011 participants. Completed in 23 January 2024.

Timeline
8 February 2023
Primary endpoint
28 November 2023
23 January 2024

Quick facts

Lead sponsorGilead Sciences
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment2,011
Start date8 February 2023
Primary completion28 November 2023
Estimated completion23 January 2024
Sites113 locations across Japan, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

Adults 12 to 64, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Coronavirus Disease 2019 (COVID-19) Symptom Alleviation by Day 29 Primary · First dose date up to 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

GroupValue95% CI
Obeldesivir5.95.4 – 6.1
Placebo6.05.8 – 6.3
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Primary · First dose date up to Day 5 plus 30 days

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.

GroupValue95% CI
Obeldesivir5.4
Placebo5.7
Percentage of Participants Experiencing Laboratory Abnormalities Primary · First dose date up to Day 5 plus 30 days

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.

Any grade
GroupValue95% CI
Obeldesivir77.5
Placebo78.5
Grade 3 or 4
GroupValue95% CI
Obeldesivir6.1
Placebo8.5
Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation Primary · First dose date up to Day 5 plus 30 days

Percentages were rounded off.

SAEs
GroupValue95% CI
Obeldesivir0.2
Placebo0.4
AEs leading to study drug discontinuation
GroupValue95% CI
Obeldesivir0.1
Placebo0
Time to COVID-19 Symptom Resolution by Day 29 Secondary · Day 1 up to 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.

GroupValue95% CI
Obeldesivir9.28.9 – 10.0
Placebo9.38.9 – 10.1
Percentage of Participants With Moderate Relapse of COVID-19 Symptoms by Day 29 Secondary · Up to 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.

GroupValue95% CI
Obeldesivir8.36.4 – 10.5
Placebo9.07.1 – 11.3
Percentage of Participants With COVID-19 Related Medically Attended Visits (MAVs) or All-cause Death by Day 29 Secondary · Up to 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.

GroupValue95% CI
Obeldesivir0.10.0 – 0.3
Placebo0.20.0 – 0.5
Percentage of Participants With COVID-19 Related Hospitalization or All-cause Death by Day 29 Secondary · Up to 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 reaso

GroupValue95% CI
Obeldesivir0
Placebo0
Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 Secondary · Day 5
GroupValue95% CI
Obeldesivir-2.69± 0.019
Placebo-2.71± 0.020
Time to Antigen Negativity Secondary · Day 1 up to Day 29

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.

GroupValue95% CI
Obeldesivir5.03.0 – 6.0
Placebo5.04.0 – 6.0
Percentage of Participants With Viral Antigen Rebound Secondary · Up to Day 29

Viral antigen rebound was defined as any positive SARS-CoV-2 rapid antigen test after antigen negativity. Percentages were rounded off.

GroupValue95% CI
Obeldesivir1.50.8 – 2.6
Placebo1.71.0 – 2.9
Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) Secondary · Day 1, 0.75 hour and 2 hours; Day 3, Predose and 0.75 hour; Day 5, Predose and 0.75 hour
Day 1 (0.75 h)
GroupValue95% CI
Obeldesivir2528.97± 5633.223
Day 1 (2 h)
GroupValue95% CI
Obeldesivir2390.68± 4763.877
Day 3 (Predose)
GroupValue95% CI
Obeldesivir1103.79± 6500.997
Day 3 (0.75 h)
GroupValue95% CI
Obeldesivir3339.59± 11353.578
Day 5 (Predose)
GroupValue95% CI
Obeldesivir2599.61± 29678.065
Day 5 (0.75 h)
GroupValue95% CI
Obeldesivir4595.37± 30772.089

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events and All-Cause Mortality: Up to 35 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Obeldesivir
Serious: 2/979 (0%)
Deaths: 0/1005
Placebo
Serious: 4/976 (0%)
Deaths: 0/1006

Serious adverse events (6 terms)

ReactionSystemObeldesivirPlacebo
Gastroenteritis bacterialInfections and infestations
Transient ischaemic attackNervous system disorders
Abortion spontaneousPregnancy, puerperium and perinatal conditions
Ectopic pregnancyPregnancy, puerperium and perinatal conditions
Bipolar disorderPsychiatric disorders
HypertensionVascular disorders

Most-reported serious reactions: Gastroenteritis bacterial, Transient ischaemic attack, Abortion spontaneous, Ectopic pregnancy, Bipolar disorder, Hypertension.

Data from ClinicalTrials.gov NCT05715528 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys.
    Mackman RL, Kalla RV, Babusis D, Pitts J, et al · · 2023 · cited 50× · PMID 37596939 · DOI 10.1021/acs.jmedchem.3c00750
  2. COVID-19 therapeutics.
    Focosi D, Franchini M, Maggi F, Shoham S. · · 2024 · cited 32× · PMID 38771027 · DOI 10.1128/cmr.00119-23
  3. Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses.
    Meyerowitz EA, Li Y. · · 2024 · cited 13× · PMID 37949817 · DOI 10.1093/cid/ciad685
  4. Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.
    Hurwitz SJ, De R, LeCher JC, Downs-Bowen JA, et al · · 2024 · cited 4× · PMID 38675992 · DOI 10.3390/v16040651
  5. Efficacy and safety of obeldesivir in low-risk, non-hospitalised patients with COVID-19 (OAKTREE): a phase 3, randomised, double-blind, placebo-controlled study.
    Ogbuagu O, Goldman JD, Gottlieb RL, Singh U, et al · · 2025 · cited 3× · PMID 40675167 · DOI 10.1016/s1473-3099(25)00238-5
  6. Anti-SARS-CoV-2 prodrug ATV006 has broad-spectrum antiviral activity against human and animal coronaviruses.
    Xu T, Li K, Huang S, Ivanov KI, et al · · 2025 · cited 2× · PMID 40487635 · DOI 10.1016/j.apsb.2025.02.028
  7. Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys.
    Pitts J, Zamora JLR, Manhas S, Aeschbacher T, et al · · 2025 · cited 1× · PMID 40645925 · DOI 10.1038/s41467-025-61595-3
  8. SARS-CoV-2 resistance analyses from the Phase 3 OAKTREE study of obeldesivir in low-risk nonhospitalized participants with COVID-19.
    Rodriguez L, Hu Y, Li J, Han D, et al · · 2026 · PMID 41475511 · DOI 10.1016/j.antiviral.2025.106339

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05715528.

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