Study of Obeldesivir in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness

Study Overview
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Brief Summary
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The goal of this clinical study is to test how well the study drug, obeldesivir (formerly GS-5245), works and how safe it is in treating coronavirus disease 2019 (COVID-19) in participants that have a higher risk of getting a serious illness.

Official Title
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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 Participants With High-Risk for Disease Progression

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Obeldesivir
* Drug: Obeldesivir Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by PCR or an approved alternative assay (eg. Rapid Antigen Test) ≤ 5 days before randomization. Serologic tests will not be accepted. Initial onset of COVID-19 signs/symptoms ≤ 5 days before randomization. Not currently hospitalized or requiring hospitalization. Presence of ≥ 1 risk factor (if unvaccinated) or ≥ 2 risk factors (if vaccinated at any point) for progression to severe disease. Key Exclusion Criteria: Anticipated use of COVID-19 therapies during the current COVID-19 illness. Received any direct acting antiviral drug against SARS-CoV-2 for the treatment of COVID-19 < 28 days or < 5 half-lives, whichever is longer, before randomization. Anticipated need for hospitalization < 48 hours after randomization. New oxygen requirement < 24 hours before randomization. Decompensated cirrhosis (Child-Pugh class B or C) or acute liver injury/failure. Undergoing dialysis, or history of moderate to severe renal impairment. Pregnant or breastfeeding (nursing). Unwilling to use protocol-mandated birth control. Received an approved, authorized or investigational COVID-19 vaccine (including booster dose) <120 days before randomization. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obeldesivir<br>Participants will receive obeldesivir 350 mg twice daily for 5 days. | Drug: Obeldesivir<br>* Tablets administered orally without regard to food.<br>* Other names: GS-5245;|
| Placebo Comparator: Placebo<br>Participants will receive placebo twice daily for 5 days. | Drug: Obeldesivir Placebo<br>* Placebo tablets administered orally without regard to food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Coronavirus Disease 2019 (COVID-19)- Related Hospitalizations or All-cause Death by Day 29 |  | First dose date up to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Of Participants With Treatment-Emergent Adverse Events |  | First dose date up to Day 5 plus 30 days | 
| Percentage of Participants Experiencing Laboratory Abnormalities |  | 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 |  | First dose date up to Day 5 plus 30 days | 
| Proportion of Participants With All-cause Hospitalization by Day 29 |  | First dose date up to Day 29 | 
| Proportion of Participants With COVID-19-related Medically Attended Visits (MAVs) or All-cause Death by Day 29 |  | First dose date up to Day 29 | 
| Proportion of Participants With COVID-19-related MAVs by Day 29 |  | First dose date up to Day 29 | 
| Proportion of Participants With All-cause Death by Day 29 |  | First dose date up to Day 29 | 
| Time to COVID-19 Symptom Alleviation by Day 15 |  | First dose date up to Day 15 | 
| Change from Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 |  | Baseline, Day 5 | 
| Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) |  | Day 1 and Day 5 | 
| Pharmacokinetic (PK) Parameter: AUCtau of GS-441524 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval | Day 1 and 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 |