COVID-19
Conditions
Brief summary
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.
Interventions
DRUGRDV
Administered as an intravenous infusion
DRUGPlacebo to Match RDV
Administered as an intravenous infusion
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Randomization up to 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. |
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | First dose date up to last dose date (maximum: 3 days) plus 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With COVID-19 Related Hospitalization at Day 28 | Randomization up to 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. |
| Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14 | Randomization up to 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. |
| Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14 | Randomization up to 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. |
| 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 | Randomization up to 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. |
| 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) | First Dose Date up to Day 14 | 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. |
| Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire | First dose date up to Day 28 | 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). |
| Percentage of Participants Who Required Oxygen Supplementation by Day 28 | Randomization up to Day 28 | — |
| Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7 | Baseline up 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. |
| Percentage of Participants Who Died by Day 28 | Randomization up to Day 28 | — |
Countries
Denmark, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and the United States. The first participant was screened on 18 September 2020. The last study visit occurred on 06 May 2021.
Pre-assignment details
630 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Remdesivir Participants received a single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3. | 279 |
| Placebo Participants received IV PTM RDV on Days 1 to 3. | 283 |
| Total | 562 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Investigator's Discretion | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Randomized and Never Treated | 13 | 9 |
| Overall Study | Withdrew Consent | 5 | 4 |
Baseline characteristics
| Characteristic | Total | Remdesivir | Placebo |
|---|---|---|---|
| Age, Continuous | 50 Years STANDARD_DEVIATION 15.1 | 50 Years STANDARD_DEVIATION 15.3 | 51 Years STANDARD_DEVIATION 14.8 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 235 Participants | 123 Participants | 112 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 304 Participants | 146 Participants | 158 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 23 Participants | 10 Participants | 13 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 36 Participants | 15 Participants | 21 Participants |
| Race/Ethnicity, Customized Race Asian | 13 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Black | 42 Participants | 20 Participants | 22 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 13 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 452 Participants | 228 Participants | 224 Participants |
| Region of Enrollment Denmark | 10 Participants | 5 Participants | 5 Participants |
| Region of Enrollment Spain | 17 Participants | 7 Participants | 10 Participants |
| Region of Enrollment United Kingdom | 4 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 531 Participants | 264 Participants | 267 Participants |
| Sex: Female, Male Female | 269 Participants | 131 Participants | 138 Participants |
| Sex: Female, Male Male | 293 Participants | 148 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 292 | 1 / 292 |
| other Total, other adverse events | 48 / 279 | 49 / 283 |
| serious Total, serious adverse events | 5 / 279 | 19 / 283 |
Outcome results
Primary
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.
Time frame: First dose date up to last dose date (maximum: 3 days) plus 30 days
Population: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | 42.3 percentage of participants |
| Placebo | Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | 46.3 percentage of participants |
Primary
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.
Time frame: Randomization up to Day 28
Population: Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | 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 | 0.7 percentage of participants |
| Placebo | 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 | 5.4 percentage of participants |
p-value: 0.007695% CI: [0.031, 0.586]Regression, Cox
Secondary
Percentage of Participants Who Died by Day 28
Time frame: Randomization up to Day 28
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants Who Died by Day 28 | 0 percentage of participants |
| Placebo | Percentage of Participants Who Died by Day 28 | 0 percentage of participants |
Secondary
Percentage of Participants Who Required Oxygen Supplementation by Day 28
Time frame: Randomization up to Day 28
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants Who Required Oxygen Supplementation by Day 28 | 0.4 percentage of participants |
| Placebo | Percentage of Participants Who Required Oxygen Supplementation by Day 28 | 1.8 percentage of participants |
p-value: 0.2163Fisher Exact
Secondary
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.
Time frame: Randomization up to Day 28
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants With COVID-19 Related Hospitalization at Day 28 | 0.7 percentage of participants |
| Placebo | Percentage of Participants With COVID-19 Related Hospitalization at Day 28 | 5.4 percentage of participants |
Secondary
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.
Time frame: Randomization up to Day 14
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14 | 0.7 percentage of participants |
| Placebo | Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14 | 5.4 percentage of participants |
p-value: 0.007695% CI: [0.031, 0.586]Regression, Cox
Secondary
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.
Time frame: Randomization up to Day 14
Population: Participants in the modified Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14 | 0.8 percentage of participants |
| Placebo | Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14 | 8.0 percentage of participants |
p-value: 0.001995% CI: [0.023, 0.43]Regression, Cox
Secondary
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.
Time frame: Randomization up to Day 28
Population: Modified Full Analysis Set included all participants who were randomized into the study, and received at least 1 dose of study treatment, and enrolled under protocol amendment 2 or later.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | 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 | 1.7 percentage of participants |
| Placebo | 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 | 8.5 percentage of participants |
p-value: 0.002495% CI: [0.065, 0.555]Regression, Cox
Secondary
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).
Time frame: First dose date up to Day 28
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir | Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire | 30.4 percentage of participants |
| Placebo | Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire | 13.3 percentage of participants |
Secondary
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.
Time frame: First Dose Date up to Day 14
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir | 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) | NA days |
| Placebo | 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) | NA days |
p-value: 0.298795% CI: [0.733, 2.693]Log Rank
Secondary
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.
Time frame: Baseline up to Day 7
Population: Participants in the Virology Analysis Set (all the participants who were randomized into the study, received at least 1 dose of study treatment, and had positive SARS-CoV-2 viral load at baseline) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remdesivir | Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7 | -1.24 log10 copies/ mililiter (mL) | Standard Deviation 1.123 |
| Placebo | Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7 | -1.14 log10 copies/ mililiter (mL) | Standard Deviation 1.099 |
p-value: 0.431895% CI: [-0.1, 0.24]ANCOVA