Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia (NCT NCT04409262)

Last Updated: 2022-02-14

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

649 participants

Primary outcome timeframe

Up to Day 28

Results posted on

2022-02-14

Participant Flow

Participants with severe COVID-19 pneumonia

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	215	434
Overall Study COMPLETED	140	300
Overall Study NOT COMPLETED	75	134

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	0	2
Overall Study Death	55	97
Overall Study Lost to Follow-up	12	23
Overall Study Lack of Staff	0	1
Overall Study Protocol Violation	3	1
Overall Study Withdrawal by Subject	5	10

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remdesivir + Placebo (RDV+PBO) n=215 Participants 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.	Remdesivir + Tocilizumab (RDV+TCZ) n=434 Participants 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.	Total n=649 Participants Total of all reporting groups
Age, Continuous	58.2 Years STANDARD_DEVIATION 13.6 • n=5 Participants	60.1 Years STANDARD_DEVIATION 13.3 • n=7 Participants	59.5 Years STANDARD_DEVIATION 13.4 • n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants	167 Participants n=7 Participants	240 Participants n=5 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	267 Participants n=7 Participants	409 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	125 Participants n=5 Participants	209 Participants n=7 Participants	334 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	88 Participants n=5 Participants	208 Participants n=7 Participants	296 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	17 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	17 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	52 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) White	154 Participants n=5 Participants	282 Participants n=7 Participants	436 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	63 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 28

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Time to Hospital Discharge or "Ready for Discharge" up to Day 28	14.0 days Interval 11.0 to 16.0	14.0 days Interval 12.0 to 15.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Time to Mechanical Ventilation or Death up to Day 28	NA Days Value not estimable due to insufficient number of events	NA Days Value not estimable due to insufficient number of events

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=428 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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	54.0 Percentage of Participants
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	2.6 Percentage of Participants
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	8.9 Percentage of Participants
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	9.6 Percentage of Participants
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	4.9 Percentage of Participants
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	10.0 Percentage of Participants
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	10.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to Day 28

Time to death is defined as the time from randomization to death.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Time to Death up to Day 28	NA Days Value not estimable due to insufficient number of events	NA Days Value not estimable due to insufficient number of events

SECONDARY outcome

Timeframe: Up to Day 60

Time to death is defined as the time from randomization to death.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Time to Death up to Day 60	NA Days Value not estimable due to insufficient number of events	NA Days Value not estimable due to insufficient number of events

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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 Interval 10.0 to 13.0	12.0 Days Interval 11.0 to 13.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=428 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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	19.4 Percentage of participants
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	5.6 Percentage of participants
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	20.1 Percentage of participants
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	29.4 Percentage of participants
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	10.0 Percentage of participants
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	12.1 Percentage of participants
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	3.3 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=428 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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	64.3 Percentage of Participants
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	1.2 Percentage of Participants
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	4.7 Percentage of Participants
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	4.4 Percentage of Participants
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	5.6 Percentage of Participants
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	5.8 Percentage of Participants
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	14.0 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=428 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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	66.4 Percentage of Participants
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	1.4 Percentage of Participants
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	3.5 Percentage of Participants
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	3.0 Percentage of Participants
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	3.7 Percentage of Participants
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	3.7 Percentage of Participants
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	18.2 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=428 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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	1.6 Percentage of Participants
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	72.2 Percentage of Participants
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	0.7 Percentage of Participants
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	1.4 Percentage of Participants
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	0.7 Percentage of Participants
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	0.7 Percentage of Participants
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	22.7 Percentage of Participants

SECONDARY outcome

Timeframe: Day 28 and Day 60

Population: The analysis population for this endpoint included only participants not on 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=188 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=371 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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 Interval 23.3 to 36.3	27.5 Percentage of Participants Interval 23.0 to 32.0
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 Interval 24.7 to 38.0	28.8 Percentage of Participants Interval 24.2 to 33.5

SECONDARY outcome

Timeframe: Day 28 and Day 60

Population: The analysis population for this endpoint included only participants on mechanical ventilation at baseline.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=22 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=59 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
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 Interval 33.7 to 75.4	40.7 Percentage of Participants Interval 28.1 to 53.2
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 Interval 43.5 to 83.7	47.5 Percentage of Participants Interval 34.7 to 60.2

SECONDARY outcome

Timeframe: Up to Day 28

Population: The analysis population for this endpoint included only participants on mechanical ventilation at baseline.

Participants who die by Day 28 are assigned a duration of 28 days.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=22 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=59 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Duration of Mechanical Ventilation (Participants Requiring Mechanical Ventilation at Baseline) up to Day 28	16.7 Days Interval 11.9 to 21.5	19.6 Days Interval 16.8 to 22.4

SECONDARY outcome

Timeframe: Days 14, 28, and 60

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Difference in Mortality at Days 14, 28, and 60 Day 14	9.5 Percentage of Participants Interval 5.6 to 13.5	10.0 Percentage of Participants Interval 7.2 to 12.8
Difference in Mortality at Days 14, 28, and 60 Day 28	19.5 Percentage of Participants Interval 14.2 to 24.9	18.1 Percentage of Participants Interval 14.5 to 21.8
Difference in Mortality at Days 14, 28, and 60 Day 60	25.7 Percentage of Participants Interval 19.8 to 31.6	22.6 Percentage of Participants Interval 18.6 to 26.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Time to Recovery up to Day 28	13.0 Days Interval 10.0 to 15.0	13.0 Days Interval 11.0 to 14.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Proportion of Participants Who Are Discharged or "Ready for Discharge" up to Day 28	67.1 Percentage of participants Interval 60.8 to 73.5	66.0 Percentage of participants Interval 61.6 to 70.5

SECONDARY outcome

Timeframe: Up to Day 28

Participants already on mechanical ventilation at baseline are only counted as an event if death occurs.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=210 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=430 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Proportion of Participants Who Require Initiation of Mechanical Ventilation Post-baseline or Die up to Day 28	29.0 Percentage of participants Interval 22.9 to 35.2	28.6 Percentage of participants Interval 24.3 to 32.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=213 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=429 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity Grade 1	9.9 Percentage of participants	10.5 Percentage of participants
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity Grade 2	21.1 Percentage of participants	28.2 Percentage of participants
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity Grade 3	10.3 Percentage of participants	11.2 Percentage of participants
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity Grade 4	4.2 Percentage of participants	4.9 Percentage of participants
Percentage of Participants With Adverse Events (AEs) Tabulated by Severity Grade 5	25.8 Percentage of participants	22.6 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Remdesivir + Placebo (RDV+Placebo) - mITT Population n=213 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.	Remdesivir + Tocilizumab (RDV+TCZ) - mITT Population n=429 Participants The mITT population included all randomized participants who received any amount of TCZ or placebo (PBO), with participants grouped according to treatment assigned at randomization.
Proportion of Participants With Any Post-Treatment Infection Serious infections	27.7 Percentage of Participants	22.6 Percentage of Participants
Proportion of Participants With Any Post-Treatment Infection Infections	35.7 Percentage of Participants	33.3 Percentage of Participants
Proportion of Participants With Any Post-Treatment Infection Opportunistic infections	2.3 Percentage of Participants	1.4 Percentage of Participants

Adverse Events

Remdesivir + Placebo (RDV+PBO)

Serious events: 76 serious events

Other events: 70 other events

Deaths: 55 deaths

Remdesivir + Tocilizumab (RDV+TCZ)

Serious events: 141 serious events

Other events: 144 other events

Deaths: 97 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Remdesivir + Placebo (RDV+PBO) n=213 participants at risk 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.	Remdesivir + Tocilizumab (RDV+TCZ) n=429 participants at risk 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.
Blood and lymphatic system disorders Anaemia	6.6% 14/213 • Number of events 15 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	3.0% 13/429 • Number of events 13 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Gastrointestinal disorders Constipation	11.7% 25/213 • Number of events 25 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	12.6% 54/429 • Number of events 54 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Infections and infestations Urinary tract infection	5.2% 11/213 • Number of events 11 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	4.7% 20/429 • Number of events 21 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Investigations Transaminases increased	4.7% 10/213 • Number of events 10 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	5.8% 25/429 • Number of events 25 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Metabolism and nutrition disorders Hyperglycaemia	4.2% 9/213 • Number of events 9 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	5.1% 22/429 • Number of events 22 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Metabolism and nutrition disorders Hypokalaemia	2.8% 6/213 • Number of events 9 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	5.4% 23/429 • Number of events 26 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Renal and urinary disorders Acute kidney injury	5.2% 11/213 • Number of events 11 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	5.6% 24/429 • Number of events 25 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.
Vascular disorders Hypotension	5.6% 12/213 • Number of events 12 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.	4.4% 19/429 • Number of events 19 • Up to Day 60 The safety analysis population consisted of all participants who received any amount of study medication (RDV and/or TCZ/PBO). Participants were grouped according to the treatment received rather than by the treatment assigned at randomization. Participants that only received RDV and did not receive TCZ/PBO were included in the RDV+PBO arm of the safety population.

Additional Information

Medical Communications

Hoffmann - La Roche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER