COVID-19
Conditions
Brief summary
The primary objective of this study was to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale on Day 11.
Interventions
DRUGRemdesivir
Administered as an intravenous infusion
DRUGStandard of Care
Standard of Care Treatment for COVID-19 Infection
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 prior to performing study procedures (participants ≥ 18 years of age) or assent (participants ≥ 12 and \< 18 years of age) prior to performing study procedures. For participants ≥ 12 and \< 18 years of age, a parent or legal guardian willing and able to provide written informed consent prior to performing study procedures * Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 4 days before randomization * Currently hospitalized and requiring medical care for COVID-19 * Peripheral capillary oxygen saturation (SpO2) \> 94% on room air at screening * Radiographic evidence of pulmonary infiltrates Key
Exclusion criteria
* Participation in any other clinical trial of an experimental treatment for COVID-19 * Concurrent treatment or planned concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 * Requiring mechanical ventilation at screening * Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN) * Creatinine clearance \< 50 mL/min using the Cockcroft-Gault formula for participants ≥ 18 years of age {Cockcroft 1976} and Schwartz Formula for participants \< 18 years of age Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Day 11 | Clinical status was derived from death, hospital discharge, and ordinal scale as follows: score of 1 was used for all days on or after the date of death; score of 7 was used for all days on or after discharged alive date; last available assessment for missing value. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol remdesivir administration; 7. Not hospitalized. The odds ratio represents the odds of improvement in the ordinal scale for a RDV group relative to the SOC group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | First dose date up to last dose date (maximum: 10 days) plus 30 days | TEAEs were defined as the following: any AE with an onset date on or after the study treatment start date and no later than 30 days after permanent discontinuation of study treatment and/or any AE leading to premature discontinuation of study treatment. For participants randomized to the SOC group, all AEs reported on or after the protocol-specified Day 1 visit were considered as treatment emergent. |
Countries
China, France, Germany, Hong Kong, Italy, Japan, Netherlands, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Europe, and Asia. The first participant was screened on 15 March 2020. The last study visit occurred on 26 June 2020.
Pre-assignment details
1138 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Remdesivir for 5 Days Participants received continued SOC therapy together with IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2-5. | 191 |
| Part A: Remdesivir for 10 Days Participants received continued SOC therapy together with IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2-10. | 193 |
| Part A: SOC Therapy Participants received continued SOC therapy. | 200 |
| Part B: Extension Treatment, Remdesivir for 10 Days Participants received continued SOC therapy together with IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2-10. | 503 |
| Total | 1,087 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 4 | 12 |
| Overall Study | Lost to Follow-up | 8 | 12 | 12 | 48 |
| Overall Study | Non-Compliance with Study Drug | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 |
| Overall Study | Randomized but not Treated | 8 | 4 | 0 | 14 |
| Overall Study | Withdrew Consent | 2 | 2 | 5 | 6 |
Baseline characteristics
| Characteristic | Part A: Remdesivir for 10 Days | Part A: SOC Therapy | Part B: Extension Treatment, Remdesivir for 10 Days | Total | Part A: Remdesivir for 5 Days |
|---|---|---|---|---|---|
| Age, Customized Age, Categorical < 65 Years | 141 Participants | 142 Participants | 351 Participants | 776 Participants | 142 Participants |
| Age, Customized Age, Categorical >= 65 Years | 52 Participants | 58 Participants | 152 Participants | 311 Participants | 49 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 42 Participants | 34 Participants | 156 Participants | 257 Participants | 25 Participants |
| Race/Ethnicity, Customized Ethnicity Missing | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 144 Participants | 152 Participants | 325 Participants | 783 Participants | 162 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 7 Participants | 13 Participants | 22 Participants | 46 Participants | 4 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 1 Participants | 3 Participants | 6 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 31 Participants | 37 Participants | 61 Participants | 163 Participants | 34 Participants |
| Race/Ethnicity, Customized Race Black | 37 Participants | 27 Participants | 107 Participants | 206 Participants | 35 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 5 Participants | 7 Participants | 21 Participants | 38 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Other | 12 Participants | 15 Participants | 50 Participants | 82 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 107 Participants | 112 Participants | 260 Participants | 588 Participants | 109 Participants |
| Region of Enrollment France | 1 Participants | 0 Participants | 5 Participants | 8 Participants | 2 Participants |
| Region of Enrollment Germany | 6 Participants | 8 Participants | 13 Participants | 35 Participants | 8 Participants |
| Region of Enrollment Hong Kong | 11 Participants | 7 Participants | 1 Participants | 28 Participants | 9 Participants |
| Region of Enrollment Italy | 23 Participants | 26 Participants | 54 Participants | 133 Participants | 30 Participants |
| Region of Enrollment Japan | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 0 Participants |
| Region of Enrollment Netherlands | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Singapore | 6 Participants | 9 Participants | 14 Participants | 32 Participants | 3 Participants |
| Region of Enrollment South Korea | 4 Participants | 10 Participants | 16 Participants | 37 Participants | 7 Participants |
| Region of Enrollment Spain | 28 Participants | 31 Participants | 44 Participants | 140 Participants | 37 Participants |
| Region of Enrollment Sweden | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants |
| Region of Enrollment Switzerland | 5 Participants | 6 Participants | 3 Participants | 18 Participants | 4 Participants |
| Region of Enrollment Taiwan | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 9 Participants | 17 Participants | 27 Participants | 60 Participants | 7 Participants |
| Region of Enrollment United States | 99 Participants | 85 Participants | 318 Participants | 578 Participants | 76 Participants |
| Sex: Female, Male Female | 75 Participants | 75 Participants | 221 Participants | 448 Participants | 77 Participants |
| Sex: Female, Male Male | 118 Participants | 125 Participants | 282 Participants | 639 Participants | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 191 | 3 / 193 | 4 / 200 | 13 / 503 |
| other Total, other adverse events | 41 / 191 | 42 / 193 | 30 / 200 | 113 / 503 |
| serious Total, serious adverse events | 9 / 191 | 10 / 193 | 18 / 200 | 40 / 503 |
Outcome results
Primary
Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11
Clinical status was derived from death, hospital discharge, and ordinal scale as follows: score of 1 was used for all days on or after the date of death; score of 7 was used for all days on or after discharged alive date; last available assessment for missing value. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring low flow supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol remdesivir administration; 7. Not hospitalized. The odds ratio represents the odds of improvement in the ordinal scale for a RDV group relative to the SOC group.
Time frame: Day 11
Population: Full Analysis Set (FAS) included all participants who were randomized into Part A of the study and received at least 1 dose of study treatment if randomized to 1 of the RDV treatment groups. Participants in the SOC arm who had protocol Day 1 visit were included in the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 2 | 0.0 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 5 | 19.9 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 4 | 3.7 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 1 | 0.0 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 7 | 70.2 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 6 | 3.7 percentage of participants |
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 3 | 2.6 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 4 | 6.2 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 1 | 1.0 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 2 | 0.5 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 3 | 0.0 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 5 | 22.8 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 6 | 4.7 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 7 | 64.8 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 5 | 23.0 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 2 | 2.0 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 7 | 60.0 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 6 | 4.0 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 4 | 5.5 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 3 | 3.5 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants in Each Clinical Status Category as Assessed by a 7-Point Ordinal Scale on Day 11 | Score: 1 | 2.0 percentage of participants |
Comparison: Primary analysisp-value: 0.017495% CI: [1.092, 2.483]Proportional odds model
Comparison: Primary analysisp-value: 0.182695% CI: [0.88, 1.952]Proportional odds model
Comparison: Secondary analysisp-value: 0.016895% CI: [1.095, 2.497]Proportional odds model
Comparison: Secondary analysisp-value: 0.218695% CI: [0.862, 1.917]Proportional odds model
Secondary
Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as the following: any AE with an onset date on or after the study treatment start date and no later than 30 days after permanent discontinuation of study treatment and/or any AE leading to premature discontinuation of study treatment. For participants randomized to the SOC group, all AEs reported on or after the protocol-specified Day 1 visit were considered as treatment emergent.
Time frame: First dose date up to last dose date (maximum: 10 days) plus 30 days
Population: Safety Analysis Set included participants who were randomized into part A of the study and received at least 1 dose of study treatment or completed the Day 1 visit (SOC only group).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Remdesivir for 5 Days | Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | 51.3 percentage of participants |
| Part A: Remdesivir for 10 Days | Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | 58.5 percentage of participants |
| Part A: SOC Therapy | Part A: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | 46.5 percentage of participants |
p-value: 0.363395% CI: [-5.2, 14.7]Fisher Exact
p-value: 0.020195% CI: [1.6, 21.8]Fisher Exact