Study of Obeldesivir in Nonhospitalized Participants With COVID-19

Study Overview
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Brief Summary
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The goal of this clinical study is to test if obeldesivir (formerly 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.

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 Nonhospitalized Participants

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: 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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 64 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: Triple


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>* Tablet administered orally without regard to food.<br>* Other names: GS-5245;|
| Placebo Comparator: Obeldesivir Placebo<br>Participants will receive obeldesivir placebo twice daily for 5 days. | Drug: Obeldesivir Placebo<br>* Tablet 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 |
| --- | --- | --- |
| Time to Coronavirus Disease 2019 (COVID-19) Symptom Alleviation by Day 29 |  | First dose date up to Day 29 | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to COVID-19 Symptom Resolution by Day 29 |  | Day 1 up to 29 | 
| Proportion of Participants with COVID-19 related Medically Attended Visits (MAVs) or All-cause Death by Day 29 |  | Up to Day 29 | 
| Proportion of Participants with Moderate Relapse of COVID-19 Symptoms by Day 29 |  | Up to Day 29 | 
| Proportion of Participants with COVID-19 related Hospitalization or All-cause Death by Day 29 |  | Up to Day 29 | 
| Change from Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 |  | Baseline, Day 5 | 
| Time to Antigen Negativity |  | Day 1 up to Day 29 | 
| Proportion of Participants with Viral Antigen Rebound |  | First dose date up to Day 29 | 
| Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) |  | Day 1, Day 3, 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, Day 3, 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, Day 3, and Day 5 | 
| PK Parameter: Cmax of GS-441524 | Cmax is defined as the maximum observed plasma concentration of drug | Day 1, Day 3, and Day 5 | 
| Proportion of Participants with Relapse of COVID-19 Symptoms by Day 29 |  | Up to Day 29 |