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Sarilumab COVID-19

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ClinicalTrials.gov Identifier: NCT04327388
Recruitment Status : Completed
First Posted : March 31, 2020
Results First Posted : May 13, 2021
Last Update Posted : May 13, 2021
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Corona Virus Infection
Interventions Drug: Sarilumab SAR153191
Drug: Placebo
Enrollment 420
Recruitment Details Study was conducted at 46 active centers in 11 countries. A total of 431 participants were screened between 28 March 2020 and 02 July 2020, of which 10 participants were screen failures and 1 participant was randomized twice and thus excluded. Therefore, a total of 420 participants were randomized in the study treatment by the interactive response technology (IRT) (2:2:1 ratio) to receive sarilumab 200 milligrams (mg)/400 mg and placebo. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Randomization was stratified by severity of illness (severe disease, critical disease) and use of systemic corticosteroids (Yes/No).
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description

Sarilumab 200 mg, single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in fraction of inspired oxygen (FiO2) requirement or
  • Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Period Title: Overall Study
Started 161 173 86
Treated 159 173 84
Participants Who Received Second Dose [1] 13 11 5
Completed 141 153 75
Not Completed 20 20 11
Reason Not Completed
Adverse Event             17             18             9
Other             1             2             0
Randomized and not treated             2             0             2
[1]
Participants who met prespecified criteria as per protocol amendment 2, received a second dose of the study drug (based on the original treatment group assigned) 24 to 48 hours after the first dose.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo Total
Hide Arm/Group Description

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Total of all reporting groups
Overall Number of Baseline Participants 161 173 86 420
Hide Baseline Analysis Population Description
Analysis was performed on randomized population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 161 participants 173 participants 86 participants 420 participants
58.3  (13.7) 58.0  (14.1) 59.9  (14.8) 58.5  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 161 participants 173 participants 86 participants 420 participants
Female
52
  32.3%
74
  42.8%
30
  34.9%
156
  37.1%
Male
109
  67.7%
99
  57.2%
56
  65.1%
264
  62.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 161 participants 173 participants 86 participants 420 participants
American Indian or Alaska Native
2
   1.2%
2
   1.2%
1
   1.2%
5
   1.2%
Asian
5
   3.1%
9
   5.2%
6
   7.0%
20
   4.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   1.2%
1
   0.2%
Black or African American
3
   1.9%
5
   2.9%
1
   1.2%
9
   2.1%
White
128
  79.5%
128
  74.0%
69
  80.2%
325
  77.4%
More than one race
0
   0.0%
3
   1.7%
0
   0.0%
3
   0.7%
Unknown or Not Reported
23
  14.3%
26
  15.0%
8
   9.3%
57
  13.6%
Clinical Status: 7-point ordinal scale   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 161 participants 173 participants 86 participants 420 participants
Scale Score 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Scale Score 2
17
  10.6%
24
  13.9%
10
  11.6%
51
  12.1%
Scale Score 3
28
  17.4%
21
  12.1%
11
  12.8%
60
  14.3%
Scale Score 4
113
  70.2%
128
  74.0%
65
  75.6%
306
  72.9%
Scale Score 5
3
   1.9%
0
   0.0%
0
   0.0%
3
   0.7%
Scale Score 6
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Scale Score 7
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: 7-point ordinal scale with scores range from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Coronavirus Disease 2019 [COVID-19] related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Number of participants in each scale category were reported.
1.Primary Outcome
Title Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points
Hide Description Time to improvement of greater than or equal (>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of >=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified intention-to-treat (mITT) population which included all participants who were treated with study medication and were analyzed according to the initial treatment assigned to the participant (as randomized).
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
10.0
(9.00 to 12.00)
10.0
(9.00 to 13.00)
12.0
(9.00 to 15.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sarilumab 200 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9561
Comments [Not Specified]
Method Log-rank test
Comments Analyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.026
Confidence Interval (2-Sided) 95%
0.751 to 1.402
Estimation Comments Hazard ratio for estimation of treatment effect of each sarilumab dose versus placebo was assessed by cox proportional hazard model stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sarilumab 400 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3376
Comments [Not Specified]
Method Log-rank test
Comments Analyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.135
Confidence Interval (2-Sided) 95%
0.835 to 1.543
Estimation Comments Hazard ratio for estimation of treatment effect of each sarilumab dose versus placebo was assessed by cox proportional hazard model stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
2.Secondary Outcome
Title Percentage of Participants Who Were Alive at Day 29
Hide Description Percentage of participants who were alive at Day 29 were reported in this outcome measure.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Number
Unit of Measure: percentage of participants
89.9 91.9 91.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sarilumab 200 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6280
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments By Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-9.27 to 5.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sarilumab 400 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8478
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments By Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-6.93 to 7.41
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29
Hide Description Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity. Percentage of participants With >=1 point improvement in clinical status from Baseline at Days 4, 7, 15, 21, and 29 (assessed using the 7-point ordinal scale) were reported.
Time Frame Baseline, Days 4, 7, 15, 21, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Number
Unit of Measure: percentage of participants
Day 4 25.2 25.4 23.8
Day 7 51.6 48.6 42.9
Day 15 74.8 76.9 71.4
Day 21 80.5 81.5 85.7
Day 29 84.9 84.4 88.1
4.Secondary Outcome
Title Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score
Hide Description Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity.
Time Frame Baseline, Days 4, 7, 15, 21, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Day 4 Number Analyzed 159 participants 173 participants 84 participants
0.1  (0.9) 0.1  (1.0) 0.2  (0.9)
Day 7 Number Analyzed 159 participants 173 participants 84 participants
0.7  (1.5) 0.7  (1.6) 0.7  (1.4)
Day 15 Number Analyzed 158 participants 171 participants 83 participants
1.9  (1.8) 2.0  (1.9) 1.7  (1.8)
Day 21 Number Analyzed 155 participants 169 participants 83 participants
2.3  (1.9) 2.3  (1.9) 2.5  (1.7)
Day 29 Number Analyzed 156 participants 170 participants 83 participants
2.5  (1.9) 2.5  (1.9) 2.7  (1.6)
5.Secondary Outcome
Title Time to Resolution of Fever
Hide Description Resolution of fever was defined as body temperature less than or equal to (<=) 36.6 degree Celsius (°C) (axilla), or <=37.2°C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics/until discharge, whichever was sooner. Time to resolution of fever (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever) - date of first dose + 1. Kaplan-Meier method was used for estimation.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
8.0
(7.00 to 9.00)
9.0
(7.00 to 10.00)
7.0
(6.00 to 12.00)
6.Secondary Outcome
Title Time to Resolution of Fever and Improvement in Oxygenation
Hide Description Time to resolution of fever was defined as body temperature <=36.6°C (axilla), or <=37.2 °C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge, whichever was sooner. Improvement in oxygenation was defined as oxygen saturation (SpO2)/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to resolution of fever and improvement in oxygenation (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever and improvement in oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
9.0
(8.00 to 10.00)
10.0
(9.00 to 13.00)
8.0
(7.00 to 12.00)
7.Secondary Outcome
Title Number of Days With Fever
Hide Description Fever was defined as body temperature greater than (>) 37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period. Number of days with fever were reported. Least square (LS) mean and standard error (SE) were estimated using the analysis of covariance (ANCOVA) model with treatment group and randomization strata as fixed effects.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 143 159 77
Least Squares Mean (Standard Error)
Unit of Measure: days
1.2  (0.23) 1.3  (0.21) 1.8  (0.30)
8.Secondary Outcome
Title Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29
Hide Description NEWS2: used to standardize assessment of acute-illness severity, track clinical condition of participants and to alert clinical teams to participant deterioration. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. Percentage of participants in following clinical risk categories were reported: low risk (score 0 to 4); low to medium risk (score of 3 in any individual parameter); medium risk (score 5 to 6); high risk (score 7 to 19).
Time Frame Baseline, Days 4, 7, 15, 21, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 169 84
Measure Type: Number
Unit of Measure: percentage of participants
Baseline: Low Number Analyzed 146 participants 163 participants 79 participants
28.8 22.1 34.2
Baseline: Low to Medium Number Analyzed 146 participants 163 participants 79 participants
0 0 0
Baseline: Medium Number Analyzed 146 participants 163 participants 79 participants
34.2 37.4 27.8
Baseline: High Number Analyzed 146 participants 163 participants 79 participants
37.0 40.5 38.0
Day 4: Low Number Analyzed 159 participants 169 participants 84 participants
52.8 56.2 40.5
Day 4: Low to Medium Number Analyzed 159 participants 169 participants 84 participants
0.6 1.2 0
Day 4: Medium Number Analyzed 159 participants 169 participants 84 participants
19.5 16.6 28.6
Day 4: High Number Analyzed 159 participants 169 participants 84 participants
27.0 26.0 31.0
Day 7: Low Number Analyzed 135 participants 143 participants 74 participants
57.0 60.8 51.4
Day 7: Low to Medium Number Analyzed 135 participants 143 participants 74 participants
0 2.1 0
Day 7: Medium Number Analyzed 135 participants 143 participants 74 participants
20.0 10.5 20.3
Day 7: High Number Analyzed 135 participants 143 participants 74 participants
23.0 26.6 28.4
Day 15: Low Number Analyzed 61 participants 67 participants 36 participants
52.5 52.2 61.1
Day 15: Low to Medium Number Analyzed 61 participants 67 participants 36 participants
0 1.5 2.8
Day 15: Medium Number Analyzed 61 participants 67 participants 36 participants
21.3 19.4 13.9
Day 15: High Number Analyzed 61 participants 67 participants 36 participants
26.2 26.9 22.2
Day 21: Low Number Analyzed 29 participants 38 participants 12 participants
44.8 50.0 66.7
Day 21: Low to Medium Number Analyzed 29 participants 38 participants 12 participants
13.8 0 0
Day 21: Medium Number Analyzed 29 participants 38 participants 12 participants
24.1 21.1 8.3
Day 21: High Number Analyzed 29 participants 38 participants 12 participants
17.2 28.9 25.0
Day 29: Low Number Analyzed 14 participants 18 participants 5 participants
57.1 27.8 60.0
Day 29: Low to Medium Number Analyzed 14 participants 18 participants 5 participants
0 0 0
Day 29: Medium Number Analyzed 14 participants 18 participants 5 participants
14.3 27.8 20.0
Day 29: High Number Analyzed 14 participants 18 participants 5 participants
28.6 44.4 20.0
9.Secondary Outcome
Title Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours
Hide Description Time to NEWS2 <2 and maintained for 24 hours: time (in days) from 1st dose of study drug until 1st occurrence of NEWS score of <2 (maintained for 24 hours); calculated as: date of 1st occurrence/episode of event (NEWS score of <2) - date of 1st dose + 1. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (score of 0 or 1 was allocated) and level of consciousness (score of 0 or 3 was allocated), where 0=normal health condition to 3=worst health condition; higher score=more severity. All scores were summed to get an aggregate score which ranged from 0 to 19, with higher scores=more severity/higher risk. Kaplan-Meier method was used for analysis.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
9.0
(7.00 to 10.00)
9.0
(8.00 to 11.00)
11.0
(8.00 to 14.00)
10.Secondary Outcome
Title Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2
Hide Description The NEWS2 was used to standardize the assessment of acute-illness severity, track the clinical condition of participants, and to alert clinical teams to participant deterioration. NEWS2 score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. LS means and SE were estimated using ANCOVA model with treatment group and randomization strata as fixed effects, and baseline NEWS2 score as a covariate.
Time Frame Baseline, Days 4, 7, 15, 21, and 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 146 159 79
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
Day 4 Number Analyzed 146 participants 159 participants 79 participants
-1.07  (0.212) -1.25  (0.198) -0.36  (0.274)
Day 7 Number Analyzed 122 participants 133 participants 69 participants
-1.63  (0.265) -1.47  (0.245) -0.83  (0.338)
Day 15 Number Analyzed 55 participants 62 participants 33 participants
-2.10  (0.508) -1.83  (0.467) -2.36  (0.641)
Day 21 Number Analyzed 26 participants 34 participants 12 participants
-3.02  (0.769) -2.24  (0.676) -2.96  (1.090)
Day 29 Number Analyzed 13 participants 17 participants 5 participants
-2.57  (0.936) -1.27  (0.884) -3.64  (1.508)
11.Secondary Outcome
Title Time-to-improvement in Oxygenation
Hide Description Time-to-improvement in oxygenation was defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to improvement in oxygenation was calculated as: date of first occurrence/episode of the event (oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
6.0
(5.00 to 7.00)
6.0
(5.00 to 7.00)
7.0
(5.00 to 8.00)
12.Secondary Outcome
Title Percentage of Participants Alive Off Supplemental Oxygen at Day 29
Hide Description Supplemental oxygen was defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Number
Unit of Measure: percentage of participants
84.9 83.8 86.9
13.Secondary Outcome
Title Percentage of Days With Hypoxemia
Hide Description Hypoxemia (low level of oxygen in the blood) was defined as SpO2 <93% on room air, or required supplemental oxygen, or mechanical ventilatory support. Days meeting the criteria for hypoxemia since the first study dose were counted and the percentage of days with hypoxemia were calculated as:100*number of days with the hypoxemia divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days
73.01  (2.063) 75.10  (1.941) 76.32  (2.724)
14.Secondary Outcome
Title Percentage of Days With Supplemental Oxygen Use
Hide Description Supplemental oxygen (oxygen therapy) was defined as oxygen administration using oxygen delivery device (e.g. nasal cannula, simple face mask, non-rebreather mask, high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, extracorporeal life support, etc.). Days meeting the criteria for supplemental oxygen use since the first study dose were counted and the percentage of days with supplemental oxygen use were calculated as:100*number of days with the supplemental oxygen use divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29) . LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days
70.57  (2.082) 73.30  (1.959) 73.23  (2.748)
15.Secondary Outcome
Title Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute
Hide Description Resting respiratory rate was measured in terms of number of breaths per minute (bpm) while a person is at rest. Only the days with respiratory rate >24 breath per minute since the first dose were counted and percentage of days with respiratory rate > 24 bpm were calculated as:100*number of days with respiratory rate >24 bpm divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Hence, overall number of participants analyzed = participants evaluable for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 150 164 78
Least Squares Mean (Standard Error)
Unit of Measure: percentage of days
14.74  (1.582) 14.58  (1.485) 15.74  (2.105)
16.Secondary Outcome
Title Time to Oxygen Saturation >= 94% on Room Air
Hide Description Time to oxygen saturation >=94% on room air was defined as the time (in days) from first dose of study drug until the time of first occurrence of oxygen saturation >=94% and it was calculated as: Date of first occurrence/episode of the event (oxygen saturation >=94%) - date of first dose + 1.Kaplan-Meier method was used for estimation.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Median (95% Confidence Interval)
Unit of Measure: days
8.0
(6.00 to 10.00)
8.0
(8.00 to 11.00)
8.0
(7.00 to 11.00)
17.Secondary Outcome
Title Mean Number of Ventilator Free Days
Hide Description Mean number of ventilator free days in participants were reported.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Mean (Standard Deviation)
Unit of Measure: days
23.8  (9.4) 24.0  (8.8) 24.9  (8.6)
18.Secondary Outcome
Title Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula
Hide Description Percentage of participants With initiation of mechanical ventilation or non-invasive ventilation, or use of high flow nasal cannula were reported in this outcome measure.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 127 141 68
Measure Type: Number
Unit of Measure: percentage of participants
20.5 23.4 19.1
19.Secondary Outcome
Title Percentage of Participants Who Required Rescue Medication
Hide Description Rescue medications were defined as the immunosuppressive (methylprednisolone, dexamethasone and prednisone) therapies. During the course of the study, participant who required rescue therapy was based on the judgement of the study physician.
Time Frame Baseline to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Number
Unit of Measure: percentage of participants
13.8 15.0 22.6
20.Secondary Outcome
Title Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study
Hide Description Percentage of participants who needed ICU care until Day 29 were reported for those not in an ICU at baseline.
Time Frame Baseline to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 98 114 56
Measure Type: Number
Unit of Measure: percentage of participants
11.2 14.9 12.5
21.Secondary Outcome
Title Number of Days of Hospitalization Among Survivors (Alive Participants)
Hide Description Number of days of hospitalization among alive participants were counted at Day 60 since the first dose. LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 142 155 75
Least Squares Mean (Standard Error)
Unit of Measure: days
15.6  (0.96) 16.1  (0.91) 15.9  (1.27)
22.Secondary Outcome
Title Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Treatment-emergent AEs (TEAEs) were the AEs that developed or worsened or became serious during the TEAE period (from the time of first dose of study drug to the last dose of study drug + 60 days). SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event.
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population which included all randomized participants who were treated with the study medication and were analyzed according to the actual treatment received.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Count of Participants
Unit of Measure: Participants
42
  26.4%
51
  29.5%
20
  23.8%
23.Secondary Outcome
Title Number of Participants With Major or Opportunistic Bacterial or Fungal Infections
Hide Description Major or opportunistic bacterial or fungal infections was considered as an adverse event of special interest (AESI: defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Count of Participants
Unit of Measure: Participants
8
   5.0%
15
   8.7%
3
   3.6%
24.Secondary Outcome
Title Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection
Hide Description Grade 4 neutropenia was defined as participants with absolute neutrophil count (ANC) <500 per cubic millimeter (mm^3). Grade 4 neutropenia with concurrent invasive infection was defined as infections and infestations (in participants with Grade 4 neutropenia) within 1 week of ANC <500/mm^3 and was considered as an AESI (defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field signifies that no participants had Grade 4 neutropenia and therefore were not evaluable.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 4 neutropenia Number Analyzed 159 participants 173 participants 84 participants
3
   1.9%
6
   3.5%
0
   0.0%
Grade 4 neutropenia with concurrent invasive infection Number Analyzed 3 participants 6 participants 0 participants
0
   0.0%
0
   0.0%
25.Secondary Outcome
Title Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation
Hide Description Grade >=2 (moderate) infusion related reactions (defined as any TEAE signs or symptoms experienced by participants who received study medication within 24 hours of the start of infusion) and Grade >=2 (moderate) hypersensitivity reactions (anaphylactic reaction, hypersensitivity or angioedema and moderate reactions) were considered as AESI which was defined as an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Gastrointestinal Perforation was defined as formation of a hole through the stomach, large bowel or small intestine.
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 159 173 84
Measure Type: Count of Participants
Unit of Measure: Participants
Grade >=2 Infusion related reactions
1
   0.6%
6
   3.5%
0
   0.0%
Grade >=2 Hypersensitivity reactions
1
   0.6%
7
   4.0%
0
   0.0%
Gastrointestinal perforation
1
   0.6%
0
   0.0%
0
   0.0%
26.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets
Hide Description

Criteria for PCSA:

  • Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (male) and <=95 g/L (female); greater than or equal to (>=) 185 g/L (male) and >=165 g/L (female); and decrease from baseline >=20 g/L.
  • Leukocytes: <3.0*10^9/Liters (L) (Non-Black) or <2.0*10^9/L (black); >=16.0*10^9/L.
  • Platelets: < 100*10^9/L; >=700*10^9/L.
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 156 170 84
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin <=115 g/L (male) and <=95 g/L (female)
29
  18.6%
34
  20.0%
15
  17.9%
Hemoglobin >=185 g/L (male) and >=165 g/L (female)
0
   0.0%
0
   0.0%
0
   0.0%
Hemoglobin decrease from baseline >=20 g/L
32
  20.5%
30
  17.6%
15
  17.9%
Leukocytes <3.0*10^9/L (Non-Black) or <2.0*10^9/L (black)
19
  12.2%
31
  18.2%
1
   1.2%
Leukocytes >=16*10^9/L
13
   8.3%
21
  12.4%
6
   7.1%
Platelets <100*10^9/L
2
   1.3%
7
   4.1%
3
   3.6%
Platelets >=700*10^9/L
3
   1.9%
2
   1.2%
2
   2.4%
27.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Hide Description Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline; >= 100% change from baseline.
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 156 170 84
Measure Type: Count of Participants
Unit of Measure: Participants
Creatinine >=150 mcmol/L
15
   9.6%
15
   8.8%
5
   6.0%
>=30% change from baseline in Creatinine
31
  19.9%
30
  17.6%
10
  11.9%
>=100% change from baseline in Creatinine
6
   3.8%
7
   4.1%
3
   3.6%
28.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Hide Description
  • Alanine Aminotransferase (ALT): >3 upper limit of normal (ULN); >5 ULN; >10 ULN and >20 ULN.
  • Bilirubin: >1.5 ULN; >2 ULN.
Time Frame Baseline up to 60 days
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description:

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
Overall Number of Participants Analyzed 156 169 84
Measure Type: Count of Participants
Unit of Measure: Participants
ALT >3 ULN Number Analyzed 156 participants 168 participants 83 participants
60
  38.5%
63
  37.5%
24
  28.9%
ALT >5 ULN Number Analyzed 156 participants 168 participants 83 participants
28
  17.9%
25
  14.9%
12
  14.5%
ALT >10 ULN Number Analyzed 156 participants 168 participants 83 participants
6
   3.8%
5
   3.0%
3
   3.6%
ALT >20 ULN Number Analyzed 156 participants 168 participants 83 participants
1
   0.6%
0
   0.0%
0
   0.0%
Bilirubin >1.5 ULN Number Analyzed 156 participants 169 participants 84 participants
5
   3.2%
4
   2.4%
4
   4.8%
Bilirubin >2 ULN Number Analyzed 156 participants 169 participants 84 participants
4
   2.6%
2
   1.2%
2
   2.4%
Time Frame All AEs were collected from the time of first dose of study drug up to 60 days regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description Reported AEs and deaths were TEAEs that developed/worsened in grade or became serious during 'treatment-emergent adverse event period' (from the time of first dose of study drug to the last dose of study drug + 60 days). Analysis was performed on safety population.
 
Arm/Group Title Sarilumab 200 mg Sarilumab 400 mg Placebo
Hide Arm/Group Description

Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]):

  • Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and
  • Increase/recurrence of fever or
  • Increase/no change in FiO2 requirement or
  • Required vasopressors, ECMO or development of multi-organ dysfunction.
All-Cause Mortality
Sarilumab 200 mg Sarilumab 400 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/159 (10.69%)      18/173 (10.40%)      9/84 (10.71%)    
Hide Serious Adverse Events
Sarilumab 200 mg Sarilumab 400 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/159 (26.42%)      51/173 (29.48%)      20/84 (23.81%)    
Blood and lymphatic system disorders       
Anaemia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Blood Loss Anaemia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Leukopenia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Neutropenia  1  1/159 (0.63%)  1 3/173 (1.73%)  3 0/84 (0.00%)  0
Thrombocytopenia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Cardiac disorders       
Atrial Fibrillation  1  0/159 (0.00%)  0 0/173 (0.00%)  0 3/84 (3.57%)  3
Cardiac Arrest  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Cardio-Respiratory Arrest  1  1/159 (0.63%)  1 1/173 (0.58%)  1 0/84 (0.00%)  0
Intracardiac Thrombus  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Pulseless Electrical Activity  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Ventricular Tachycardia  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Eye disorders       
Entropion  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Gastrointestinal disorders       
Dysphagia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Gastric Ulcer Perforation  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Intra-Abdominal Haematoma  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Megacolon  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
General disorders       
Death  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Hyperthermia  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Multiple Organ Dysfunction Syndrome  1  2/159 (1.26%)  2 3/173 (1.73%)  3 3/84 (3.57%)  3
Physical Deconditioning  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Sudden Death  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Hepatobiliary disorders       
Cholelithiasis  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Hepatic Steatosis  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Hepatitis  1  1/159 (0.63%)  1 1/173 (0.58%)  1 0/84 (0.00%)  0
Hepatitis Acute  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Hepatocellular Injury  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Infections and infestations       
Abscess Limb  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Bacterial Infection  1  0/159 (0.00%)  0 1/173 (0.58%)  1 2/84 (2.38%)  2
Covid-19 Pneumonia  1  11/159 (6.92%)  11 4/173 (2.31%)  4 2/84 (2.38%)  2
Clostridium Difficile Colitis  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Cystitis Klebsiella  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Endocarditis  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Lower Respiratory Tract Infection Fungal  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Peritonitis  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Pneumonia  1  1/159 (0.63%)  1 6/173 (3.47%)  6 0/84 (0.00%)  0
Pneumonia Bacterial  1  1/159 (0.63%)  1 3/173 (1.73%)  3 1/84 (1.19%)  1
Pneumonia Klebsiella  1  1/159 (0.63%)  1 0/173 (0.00%)  0 1/84 (1.19%)  1
Sepsis  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Septic Shock  1  4/159 (2.52%)  4 4/173 (2.31%)  5 2/84 (2.38%)  2
Soft Tissue Infection  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Staphylococcal Sepsis  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Systemic Bacterial Infection  1  0/159 (0.00%)  0 2/173 (1.16%)  2 0/84 (0.00%)  0
Systemic Candida  1  0/159 (0.00%)  0 2/173 (1.16%)  2 0/84 (0.00%)  0
Tracheobronchitis  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Injury, poisoning and procedural complications       
Ankle Fracture  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Femur Fracture  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Infusion Related Reaction  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Investigations       
Alanine Aminotransferase Increased  1  4/159 (2.52%)  4 3/173 (1.73%)  3 1/84 (1.19%)  1
Metabolism and nutrition disorders       
Hyperkalaemia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Hypertriglyceridaemia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Hyponatraemia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Rhabdomyolysis  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Nervous system disorders       
Brain Oedema  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Carotid Artery Thrombosis  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Cerebrovascular Accident  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Hydrocephalus  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Hypoxic-Ischaemic Encephalopathy  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Ischaemic Stroke  1  2/159 (1.26%)  2 1/173 (0.58%)  1 0/84 (0.00%)  0
Renal and urinary disorders       
Acute Kidney Injury  1  2/159 (1.26%)  2 4/173 (2.31%)  4 0/84 (0.00%)  0
Renal Failure  1  0/159 (0.00%)  0 2/173 (1.16%)  2 0/84 (0.00%)  0
Renal Impairment  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Respiratory, thoracic and mediastinal disorders       
Acute Respiratory Failure  1  0/159 (0.00%)  0 4/173 (2.31%)  4 0/84 (0.00%)  0
Hypoxia  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Organising Pneumonia  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Pneumomediastinum  1  1/159 (0.63%)  1 0/173 (0.00%)  0 1/84 (1.19%)  1
Pneumothorax  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Pneumothorax Spontaneous  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Pulmonary Embolism  1  1/159 (0.63%)  1 2/173 (1.16%)  2 2/84 (2.38%)  2
Respiratory Arrest  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Respiratory Distress  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Respiratory Failure  1  6/159 (3.77%)  6 5/173 (2.89%)  5 3/84 (3.57%)  3
Vascular disorders       
Deep Vein Thrombosis  1  1/159 (0.63%)  1 1/173 (0.58%)  1 0/84 (0.00%)  0
Hypertensive Crisis  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
Hypotension  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Peripheral Artery Occlusion  1  0/159 (0.00%)  0 1/173 (0.58%)  1 0/84 (0.00%)  0
Thrombophlebitis Superficial  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Vena Cava Thrombosis  1  0/159 (0.00%)  0 0/173 (0.00%)  0 1/84 (1.19%)  1
Venous Thrombosis Limb  1  1/159 (0.63%)  1 0/173 (0.00%)  0 0/84 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sarilumab 200 mg Sarilumab 400 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   57/159 (35.85%)      68/173 (39.31%)      14/84 (16.67%)    
Blood and lymphatic system disorders       
Neutropenia  1  11/159 (6.92%)  11 13/173 (7.51%)  13 0/84 (0.00%)  0
Investigations       
Alanine Aminotransferase Increased  1  48/159 (30.19%)  48 58/173 (33.53%)  59 14/84 (16.67%)  14
Aspartate Aminotransferase Increased  1  11/159 (6.92%)  11 15/173 (8.67%)  16 0/84 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
Phone: 800-633-1610 ext 6#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04327388    
Other Study ID Numbers: EFC16844
2020-001162-12 ( EudraCT Number )
U1111-1249-6021 ( Other Identifier: WHO Universal Trial Reference Number )
First Submitted: March 26, 2020
First Posted: March 31, 2020
Results First Submitted: April 28, 2021
Results First Posted: May 13, 2021
Last Update Posted: May 13, 2021