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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: RDV
* Drug: Placebo to Match RDV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 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: Remdesivir (RDV)<br>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<br>* Administered as an intravenous infusion<br>* Other names: Veklury®;|
| Placebo Comparator: Placebo<br>Participants will receive IV placebo to match (PTM) RDV on Days 1 to 3. | Drug: Placebo to Match RDV<br>* Administered as an intravenous infusion<br>|

What is the study measuring?
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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 |