COVID-19 Pneumonia
Conditions
Brief summary
This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
Interventions
DRUGRemdesivir
Participants will receive intravenous (IV) RDV
DRUGTocilizumab
Participants will receive IV TCZ
DRUGPlacebo
Participants will receive IV placebo matched to TCZ
Sponsors
Gilead Sciences
Hoffmann-La Roche
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
* Hospitalized with COVID-19 pneumonia confirmed per a positive polymerase chain reaction (PCR) of any specimen (e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan * Requiring more than 6 L/min supplemental oxygen to maintain SpO2 \> 93% * Agrees to not participate in another clinical trial for the treatment of COVID-19 while participating in this study
Exclusion criteria
* Known severe allergic reactions to tocilizumab or other monoclonal antibodies * Known hypersensitivity to remdesivir, the metabolites, or formulation excipients * Active tuberculosis (TB) infection * Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) * In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments * Treatment with immunosuppressive or immunomodulatory therapy (including tocilizumab) within the past 3 months * Concurrent treatment with other agents with actual or possible direct-acting antiviral activity against SARS-CoV-2 within 24 hours prior to study drug dosing. In addition, participants with prior or current treatment with \> 2 doses of remdesivir for COVID-19 are excluded * Participating in other drug clinical trials * Estimated glomerular filtration rate (eGFR) \< 30 mL/min (including patients receiving hemodialysis or hemofiltration) * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN) detected within 24 hours of screening (according to local laboratory reference ranges) * Absolute neutrophil count (ANC) \< 1000/uL at screening * Platelet count \< 50,000/uL at screening * Body weight \< 40 kg * Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Hospital Discharge or Ready for Discharge up to Day 28 | Up to Day 28 | Defined as days from randomization to hospital discharge or Ready for Discharge not followed by ordinal scale category \>1, hospital readmission or death. Hospital discharge or Ready for Discharge is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Mechanical Ventilation or Death up to Day 28 | Up to Day 28 | Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event. |
| Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Day 14 | Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Time to Death up to Day 28 | Up to Day 28 | Time to death is defined as the time from randomization to death. |
| Time to Death up to Day 60 | Up to Day 60 | Time to death is defined as the time from randomization to death. |
| Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28 | Up to Day 28 | Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28. Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Day 7 | Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Day 21 | Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Day 28 | Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Proportion of Participants Who Are Discharged or Ready for Discharge up to Day 28 | Up to Day 28 | Defined as hospital discharge or Ready for Discharge not followed by ordinal scale category \>1, hospital readmission or death. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28 | Up to Day 28 | Participants already on mechanical ventilation at baseline are only counted as an event if death occurs. |
| Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Day 60 | Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
| Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) | Day 28 and Day 60 | Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event. Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event. |
| Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) | Day 28 and Day 60 | — |
| Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28 | Up to Day 28 | Participants who die by Day 28 are assigned a duration of 28 days. |
| Difference in Mortality at Days 14, 28, and 60 | Days 14, 28, and 60 | — |
| Time to Recovery up to Day 28 | Up to Day 28 | Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or ready for hospital ward not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category \>2 or death. Participants who die are censored at day 28. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Any Post-Treatment Infection | Up to Day 60 | — |
| Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Up to Day 60 | AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE Participants are counted at the highest AE grade experienced. |
Countries
Brazil, Russia, Spain, United States
Participant flow
Recruitment details
Participants with severe COVID-19 pneumonia
Participants by arm
| Arm | Count |
|---|---|
| Remdesivir + Placebo (RDV+PBO) Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of PBO on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of PBO was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | 215 |
| Remdesivir + Tocilizumab (RDV+TCZ) Participants were to receive a 200 mg intravenous (IV) loading dose of RDV, followed by one infusion of TCZ on Day 1. Participants were then to be given a 100 mg once daily IV maintenance dose of RDV from Days 2-10, with discontinuation at discharge whether or not 10 days of RDV dosing were completed. One additional infusion of TCZ was allowed 8-24 hours after the first for participants with sustained fever or clinically significant worsening of signs or symptoms. | 434 |
| Total | 649 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 55 | 97 |
| Overall Study | Lack of Staff | 0 | 1 |
| Overall Study | Lost to Follow-up | 12 | 23 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Remdesivir + Tocilizumab (RDV+TCZ) | Total | Remdesivir + Placebo (RDV+PBO) |
|---|---|---|---|
| Age, Continuous | 60.1 Years STANDARD_DEVIATION 13.3 | 59.5 Years STANDARD_DEVIATION 13.4 | 58.2 Years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 209 Participants | 334 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 208 Participants | 296 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants | 19 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 22 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 72 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 11 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 63 Participants | 90 Participants | 27 Participants |
| Race (NIH/OMB) White | 282 Participants | 436 Participants | 154 Participants |
| Sex: Female, Male Female | 167 Participants | 240 Participants | 73 Participants |
| Sex: Female, Male Male | 267 Participants | 409 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 55 / 213 | 97 / 429 |
| other Total, other adverse events | 70 / 213 | 144 / 429 |
| serious Total, serious adverse events | 76 / 213 | 141 / 429 |
Outcome results
Primary
Time to Hospital Discharge or Ready for Discharge up to Day 28
Defined as days from randomization to hospital discharge or Ready for Discharge not followed by ordinal scale category \>1, hospital readmission or death. Hospital discharge or Ready for Discharge is defined as an ordinal score of 1 on the 7-point ordinal scale. Participants who die are censored at Day 28. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Up to Day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Hospital Discharge or Ready for Discharge up to Day 28 | 14.0 days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Hospital Discharge or Ready for Discharge up to Day 28 | 14.0 days |
p-value: 0.741495% CI: [0.78, 1.19]Log Rank
Secondary
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14
Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Day 14
Population: Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 14 and were excluded from analysis for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 3 | 11.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 5 | 6.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 2 | 1.9 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 6 | 11.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 4 | 6.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 7 | 9.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 1 | 52.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 7 | 10.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 1 | 54.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 2 | 2.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 3 | 8.9 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 4 | 9.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 5 | 4.9 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 14 | Category 6 | 10.0 Percentage of Participants |
p-value: 0.764895% CI: [0.77, 1.44]Regression, Logistic
Secondary
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21
Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Day 21
Population: Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 21 and were excluded from analysis for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 3 | 4.8 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 5 | 6.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 2 | 1.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 6 | 7.1 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 4 | 2.9 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 7 | 14.8 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 1 | 62.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 7 | 14.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 1 | 64.3 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 2 | 1.2 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 3 | 4.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 4 | 4.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 5 | 5.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 21 | Category 6 | 5.8 Percentage of Participants |
p-value: 0.633195% CI: [0.78, 1.52]Regression, Logistic
Secondary
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28
Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Day 28
Population: Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 28 and were excluded from analysis for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 3 | 1.0 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 5 | 4.3 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 2 | 1.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 6 | 3.8 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 4 | 2.9 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 7 | 19.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 1 | 67.1 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 7 | 18.2 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 1 | 66.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 2 | 1.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 3 | 3.5 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 4 | 3.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 5 | 3.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 28 | Category 6 | 3.7 Percentage of Participants |
p-value: 0.962295% CI: [0.7, 1.4]Regression, Logistic
Secondary
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60
Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Day 60
Population: Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 60 and were excluded from analysis for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 3 | 1.0 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 5 | 0.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 2 | 1.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 6 | 0 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 4 | 1.4 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 7 | 25.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 1 | 70.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 7 | 22.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 1 | 72.2 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 2 | 0.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 3 | 1.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 4 | 1.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 5 | 0.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 60 | Category 6 | 0.7 Percentage of Participants |
p-value: 0.48595% CI: [0.79, 1.64]Regression, Logistic
Secondary
Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7
Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Day 7
Population: Two participants in the RDV+TCZ arm had no post-baseline clinical status data to Day 7 and were excluded from analysis for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 3 | 17.6 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 5 | 9.5 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 2 | 4.3 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 6 | 12.9 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 4 | 30.0 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 7 | 3.8 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 1 | 21.9 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 7 | 3.3 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 1 | 19.4 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 2 | 5.6 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 3 | 20.1 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 4 | 29.4 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 5 | 10.0 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Clinical Status as Assessed by the Investigator Using a 7-category Ordinal Scale of Clinical Status on Day 7 | Category 6 | 12.1 Percentage of participants |
p-value: 0.956995% CI: [0.75, 1.35]Regression, Logistic
Secondary
Difference in Mortality at Days 14, 28, and 60
Time frame: Days 14, 28, and 60
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 14 | 9.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 28 | 19.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 60 | 25.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 14 | 10.0 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 28 | 18.1 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Difference in Mortality at Days 14, 28, and 60 | Day 60 | 22.6 Percentage of Participants |
Comparison: Day 14p-value: 0.822295% CI: [-4.4, 5.6]Cochran-Mantel-Haenszel
Comparison: Day 28p-value: 0.694495% CI: [-7.8, 5.2]Cochran-Mantel-Haenszel
Comparison: Day 60p-value: 0.391995% CI: [-10.1, 4]Cochran-Mantel-Haenszel
Secondary
Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28
Participants who die by Day 28 are assigned a duration of 28 days.
Time frame: Up to Day 28
Population: The analysis population for this endpoint included only participants on mechanical ventilation at baseline.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28 | 16.7 Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28 | 19.6 Days |
p-value: 0.243495% CI: [-2.16, 8.38]Regression, Linear
Secondary
Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline)
Day 28: Participants who withdraw or die prior to Day 28 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 28, which are counted as an event. Day 60: Participants who withdraw or die prior to Day 60 are assumed to have required mechanical ventilation. Participants without mechanical ventilation prior to discharge are assumed not to have required mechanical ventilation unless they die by Day 60, which are counted as an event.
Time frame: Day 28 and Day 60
Population: The analysis population for this endpoint included only participants not on mechanical ventilation at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) | Day 28 | 29.8 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) | Day 60 | 31.4 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) | Day 28 | 27.5 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline (Participants Who Did Not Require Mechanical Ventilation at Baseline) | Day 60 | 28.8 Percentage of Participants |
Comparison: Day 28p-value: 0.591595% CI: [-10.2, 5.9]Cochran-Mantel-Haenszel
Comparison: Day 60p-value: 0.549495% CI: [-10.5, 5.6]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline)
Time frame: Day 28 and Day 60
Population: The analysis population for this endpoint included only participants on mechanical ventilation at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) | Day 28 | 54.5 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) | Day 60 | 63.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) | Day 28 | 40.7 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Who Are Alive and Free of Respiratory Failure at Day 28 and Day 60 (Participants Requiring Mechanical Ventilation at Baseline) | Day 60 | 47.5 Percentage of Participants |
Comparison: Day 28p-value: 0.25995% CI: [-37.4, 9.2]Cochran-Mantel-Haenszel
Comparison: Day 60p-value: 0.22995% CI: [-37, 7.8]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants Who Are Discharged or Ready for Discharge up to Day 28
Defined as hospital discharge or Ready for Discharge not followed by ordinal scale category \>1, hospital readmission or death. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Up to Day 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Who Are Discharged or Ready for Discharge up to Day 28 | 67.1 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Who Are Discharged or Ready for Discharge up to Day 28 | 66.0 Percentage of participants |
p-value: 0.769295% CI: [-8.7, 6.8]Cochran-Mantel-Haenszel
Secondary
Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28
Participants already on mechanical ventilation at baseline are only counted as an event if death occurs.
Time frame: Up to Day 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28 | 29.0 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28 | 28.6 Percentage of participants |
p-value: 0.933495% CI: [-7.8, 7.2]Cochran-Mantel-Haenszel
Secondary
Time to Death up to Day 28
Time to death is defined as the time from randomization to death.
Time frame: Up to Day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Death up to Day 28 | NA Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Death up to Day 28 | NA Days |
p-value: 0.786795% CI: [0.65, 1.39]Log Rank
Secondary
Time to Death up to Day 60
Time to death is defined as the time from randomization to death.
Time frame: Up to Day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Death up to Day 60 | NA Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Death up to Day 60 | NA Days |
p-value: 0.460295% CI: [0.63, 1.23]Log Rank
Secondary
Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28
Defined as time from randomization to the time when at least a 2-category improvement in the 7-category ordinal scale is observed. Patients who die are censored at day 28. Clinical status was assessed by the investigator according to the following ordinal scale categories: 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Up to Day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28 | 11.0 Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-category Ordinal Scale of Clinical Status up to Day 28 | 12.0 Days |
p-value: 0.866495% CI: [0.8, 1.21]Log Rank
Secondary
Time to Mechanical Ventilation or Death up to Day 28
Time to Mechanical Ventilation or Death defined as the time from randomization to the first occurrence of death or mechanical ventilation. For participants already on mechanical ventilation at baseline, only death is counted as an event.
Time frame: Up to Day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Mechanical Ventilation or Death up to Day 28 | NA Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Mechanical Ventilation or Death up to Day 28 | NA Days |
p-value: 0.899395% CI: [0.72, 1.34]Log Rank
Secondary
Time to Recovery up to Day 28
Defined as the time from randomization to the time when an ordinal scale category of 2 (non-ICU hospital ward or ready for hospital ward not requiring supplemental oxygen) or better is observed, not followed by ordinal scale category \>2 or death. Participants who die are censored at day 28. 1. Discharged (or ready for discharge as evidenced by normal temperature and respiratory rate, and stable oxygen saturation on ambient air or \</= 2L supplemental oxygen) 2. Non-intensive care unit (ICU) hospital ward (or ready for hospital ward) not requiring supplemental oxygen 3. Non-ICU hospital ward (or ready for hospital ward) requiring supplemental oxygen 4. ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen 5. ICU, requiring intubation and mechanical ventilation 6. ICU, requiring extracorporeal membrane oxygenation (ECMO) or mechanical ventilation and additional organ support (e.g., vasopressors, renal replacement therapy) 7. Death
Time frame: Up to Day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Time to Recovery up to Day 28 | 13.0 Days |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Time to Recovery up to Day 28 | 13.0 Days |
p-value: 0.677895% CI: [0.78, 1.18]Log Rank
Other Pre-specified
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity
AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AE Participants are counted at the highest AE grade experienced.
Time frame: Up to Day 60
Population: Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 2 | 21.1 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 4 | 4.2 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 3 | 10.3 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 5 | 25.8 Percentage of participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 1 | 9.9 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 5 | 22.6 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 1 | 10.5 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 2 | 28.2 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 3 | 11.2 Percentage of participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Percentage of Participants With Adverse Events (AEs) Tabulated by Severity | Grade 4 | 4.9 Percentage of participants |
Other Pre-specified
Proportion of Participants With Any Post-Treatment Infection
Time frame: Up to Day 60
Population: Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Serious infections | 27.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Infections | 35.7 Percentage of Participants |
| Remdesivir + Placebo (RDV+Placebo) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Opportunistic infections | 2.3 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Serious infections | 22.6 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Infections | 33.3 Percentage of Participants |
| Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population | Proportion of Participants With Any Post-Treatment Infection | Opportunistic infections | 1.4 Percentage of Participants |