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Investigating Otilimab in Patients With Severe Pulmonary COVID-19 Related Disease (OSCAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04376684
Recruitment Status : Completed
First Posted : May 6, 2020
Results First Posted : March 9, 2022
Last Update Posted : March 23, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Severe Acute Respiratory Syndrome
Interventions Biological: Otilimab
Biological: Placebo 1
Biological: Placebo 2
Drug: Standard of care
Enrollment 1156
Recruitment Details This was a 2-part study evaluating efficacy and safety of intravenously (IV) administered otilimab in participants with severe pulmonary Coronavirus Disease-2019 (COVID-19) related disease. Part 1 consisted of participants aged 18 to 79 years and Part 2 consisted of participants aged 70 years and older.
Pre-assignment Details A total of 1156 (806 in Part 1 and 350 in Part 2) participants were enrolled in the study (Enrolled Population: All participants who entered the study).
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Period Title: Part 1 (Up to Day 60)
Started 403 403 0 0
Completed 388 379 0 0
Not Completed 15 24 0 0
Reason Not Completed
Withdrawal by Subject             7             8             0             0
Protocol Violation             2             3             0             0
Physician Decision             2             5             0             0
Lost to Follow-up             4             8             0             0
Period Title: Part 2 (Up to Day 60)
Started 0 0 175 175
Completed 0 0 170 171
Not Completed 0 0 5 4
Reason Not Completed
Withdrawal by Subject             0             0             1             1
Physician Decision             0             0             1             1
Lost to Follow-up             0             0             3             2
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg Part 2: Placebo 2 Part 2: Otilimab 90 mg Total
Hide Arm/Group Description Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care. Total of all reporting groups
Overall Number of Baseline Participants 403 403 175 175 1156
Hide Baseline Analysis Population Description
Baseline characteristics were presented for Enrolled Population.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 403 participants 403 participants 175 participants 175 participants 1156 participants
<18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 to 64 years
249
  61.8%
250
  62.0%
0
   0.0%
0
   0.0%
499
  43.2%
>=65 to 84 years
154
  38.2%
153
  38.0%
168
  96.0%
168
  96.0%
643
  55.6%
>=85 years
0
   0.0%
0
   0.0%
7
   4.0%
7
   4.0%
14
   1.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 403 participants 403 participants 175 participants 175 participants 1156 participants
Female
128
  31.8%
101
  25.1%
75
  42.9%
73
  41.7%
377
  32.6%
Male
275
  68.2%
302
  74.9%
100
  57.1%
102
  58.3%
779
  67.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 403 participants 403 participants 175 participants 175 participants 1156 participants
American Indian or Alaska Native
24
   6.0%
30
   7.4%
3
   1.7%
8
   4.6%
65
   5.6%
Asian - Central/South Asian Heritage
42
  10.4%
31
   7.7%
1
   0.6%
0
   0.0%
74
   6.4%
Asian - East Asian Heritage
4
   1.0%
4
   1.0%
0
   0.0%
0
   0.0%
8
   0.7%
Asian - Japanese Heritage
15
   3.7%
14
   3.5%
13
   7.4%
5
   2.9%
47
   4.1%
Asian - South East Asian Heritage
12
   3.0%
8
   2.0%
1
   0.6%
0
   0.0%
21
   1.8%
Black or African American
25
   6.2%
26
   6.5%
6
   3.4%
6
   3.4%
63
   5.4%
White - Arabic/North African Heritage
27
   6.7%
21
   5.2%
14
   8.0%
21
  12.0%
83
   7.2%
White - White/Caucasian/European Heritage
235
  58.3%
251
  62.3%
136
  77.7%
134
  76.6%
756
  65.4%
Mixed Asian Race
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Mixed White Race
1
   0.2%
1
   0.2%
1
   0.6%
0
   0.0%
3
   0.3%
Multiple
7
   1.7%
7
   1.7%
0
   0.0%
0
   0.0%
14
   1.2%
Unknown
11
   2.7%
9
   2.2%
0
   0.0%
1
   0.6%
21
   1.8%
1.Primary Outcome
Title Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Hide Description Participants were considered alive and free of respiratory failure if they were in category 1, 2, 3, or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (greater than or equal to [>=]15 liters per minute [L/min]), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat (mITT) Population consisted of all randomized participants who received study intervention. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 393 389
Measure Type: Number
Unit of Measure: Percentage of participants
67 71
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0456
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.96 to 1.82
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
2.Primary Outcome
Title Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 172
Measure Type: Number
Unit of Measure: Percentage of participants
51 52
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8574
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.67 to 1.61
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
3.Secondary Outcome
Title Part 1: Number of Participants Who Died Due to All Causes at Day 60
Hide Description Number of participants who died due to all causes at Day 60 are reported.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 386 373
Measure Type: Count of Participants
Unit of Measure: Participants
93
  24.1%
84
  22.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2057
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.61 to 1.22
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
4.Secondary Outcome
Title Part 2: Number of Participants Who Died Due to All Causes at Day 28
Hide Description Number of participants who died due to all causes at Day 28 is reported
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 172
Measure Type: Count of Participants
Unit of Measure: Participants
70
  41.2%
63
  36.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3061
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.50 to 1.24
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
5.Secondary Outcome
Title Part 2: Number of Participants Who Died Due to All Causes at Day 60
Hide Description Number of participants who died due to all causes at Day 60 is reported
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 171
Measure Type: Count of Participants
Unit of Measure: Participants
76
  44.7%
74
  43.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6665
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.59 to 1.41
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
6.Secondary Outcome
Title Part 1: Time to Death Due to All Causes up to Day 60
Hide Description Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 93 84
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
<25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1942
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.65 to 1.18
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
7.Secondary Outcome
Title Part 2: Time to Death Due to All Causes up to Day 60
Hide Description Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 76 74
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(16 to NA)
NA [1] 
(16 to NA)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5324
Comments p-value is generated from a two-sided test
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.65 to 1.24
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
8.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 396 393
Measure Type: Number
Unit of Measure: Percentage of participants
42 44
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2871
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.80 to 1.49
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
9.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 394 391
Measure Type: Number
Unit of Measure: Percentage of participants
61 63
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1754
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.85 to 1.58
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
10.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 392 385
Measure Type: Number
Unit of Measure: Percentage of participants
70 74
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0616
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.93 to 1.79
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
11.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 386 373
Measure Type: Number
Unit of Measure: Percentage of participants
74 75
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1830
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.84 to 1.63
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
12.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 173 174
Measure Type: Number
Unit of Measure: Percentage of participants
28 37
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0831
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
0.95 to 2.39
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
13.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 171 174
Measure Type: Number
Unit of Measure: Percentage of participants
43 49
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2557
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.83 to 2.00
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
14.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 172
Measure Type: Number
Unit of Measure: Percentage of participants
54 54
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8560
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.67 to 1.61
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
15.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
Hide Description Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 171
Measure Type: Number
Unit of Measure: Percentage of participants
55 56
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7533
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.69 to 1.66
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
16.Secondary Outcome
Title Part 1: Time to Recovery From Respiratory Failure up to Day 28
Hide Description Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 263 281
Median (Inter-Quartile Range)
Unit of Measure: Days
10 [1] 
(5 to NA)
9 [1] 
(5 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0959
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.95 to 1.32
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
17.Secondary Outcome
Title Part 2: Time to Recovery From Respiratory Failure up to Day 28
Hide Description Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 90 91
Median (Inter-Quartile Range)
Unit of Measure: Days
24 [1] 
(7 to NA)
22 [1] 
(5 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4421
Comments p-value is generated from a two-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.84 to 1.50
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
18.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 396 393
Measure Type: Number
Unit of Measure: Percentage of participants
11 12
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2814
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.73 to 1.80
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
19.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 394 391
Measure Type: Number
Unit of Measure: Percentage of participants
37 37
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3901
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.77 to 1.42
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
20.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 393 389
Measure Type: Number
Unit of Measure: Percentage of participants
57 57
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4763
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.75 to 1.36
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
21.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 392 385
Measure Type: Number
Unit of Measure: Percentage of participants
63 66
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1973
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.84 to 1.56
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
22.Secondary Outcome
Title Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 386 373
Measure Type: Number
Unit of Measure: Percentage of participants
67 71
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1173
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.88 to 1.67
Estimation Comments Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
23.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 173 174
Measure Type: Number
Unit of Measure: Percentage of participants
3 13
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0037
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.98
Confidence Interval (2-Sided) 95%
1.57 to 10.13
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
24.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 171 174
Measure Type: Number
Unit of Measure: Percentage of participants
23 28
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3581
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.77 to 2.06
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
25.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 172
Measure Type: Number
Unit of Measure: Percentage of participants
39 38
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9621
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.63 to 1.54
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
26.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 172
Measure Type: Number
Unit of Measure: Percentage of participants
46 41
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4167
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.54 to 1.29
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
27.Secondary Outcome
Title Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
Hide Description Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame At Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 170 171
Measure Type: Number
Unit of Measure: Percentage of participants
51 46
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3408
Comments p-value is generated from a two-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.53 to 1.25
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
28.Secondary Outcome
Title Part 1: Time to Last Dependence on Supplementary Oxygen
Hide Description Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 223 221
Median (Inter-Quartile Range)
Unit of Measure: Days
22 [1] 
(11 to NA)
21 [1] 
(10 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4250
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.85 to 1.23
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
29.Secondary Outcome
Title Part 2: Time to Last Dependence on Supplementary Oxygen
Hide Description Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 66 68
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(15 to NA)
NA [1] 
(13 to NA)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4774
Comments p-value is generated from a two-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.81 to 1.59
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
30.Secondary Outcome
Title Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28
Hide Description Participants who were admitted to the ICU up to (and including) Day 28 were evaluated. Percentage values are rounded off.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population (not in ICU at Baseline) comprised of participants in the mITT population who were not in the ICU at Baseline. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 98 95
Measure Type: Number
Unit of Measure: Percentage of participants
29 16
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0119
Comments p-value is from a one-sided test.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.18 to 0.89
Estimation Comments Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
31.Secondary Outcome
Title Part 1: Time to Final ICU Discharge
Hide Description Time to final ICU discharge was defined as the time from dosing to when the participant is discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population admitted to ICU at Baseline comprised of those participants in mITT who were admitted to ICU at Baseline. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 300 300
Median (Inter-Quartile Range)
Unit of Measure: Days
13 [1] 
(7 to NA)
15 [1] 
(7 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4404
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.83 to 1.24
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
32.Secondary Outcome
Title Part 2: Time to Final ICU Discharge
Hide Description Time to final ICU discharge was defined as the time from dosing to when the participant was discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population admitted to ICU at Baseline. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 38 44
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(12 to NA)
NA [1] 
(7 to NA)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6253
Comments p-value is generated from a two-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.72 to 1.72
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
33.Secondary Outcome
Title Part 1: Time to First Discharge From Investigator Site up to Day 60
Hide Description Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site (IS) up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 288 294
Median (Inter-Quartile Range)
Unit of Measure: Days
18 [1] 
(11 to NA)
18 [1] 
(10 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1078
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.94 to 1.30
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
34.Secondary Outcome
Title Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60
Hide Description Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge to non-hospitalized residence is presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 269 280
Median (Inter-Quartile Range)
Unit of Measure: Days
21 [1] 
(12 to NA)
20 [1] 
(11 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Placebo 1, Part 1: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1140
Comments p-value is from a one-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.94 to 1.31
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
35.Secondary Outcome
Title Part 2: Time to First Discharge From Investigator Site up to Day 60
Hide Description Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 96 99
Median (Inter-Quartile Range)
Unit of Measure: Days
36 [1] 
(15 to NA)
37 [1] 
(15 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7084
Comments p-value is generated from a two-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.80 to 1.40
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
36.Secondary Outcome
Title Part 2: Time to First Discharge to Non-hospitalized Residence
Hide Description Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge to non-hospitalized residence is presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 86 90
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(18 to NA)
53 [2] 
(15 to NA)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
[2]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 2: Placebo 2, Part 2: Otilimab 90 mg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4085
Comments p-value is generated from a two-sided test.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.84 to 1.52
Estimation Comments Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
37.Secondary Outcome
Title Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)
Hide Description An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population comprised of all participants who received study intervention
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg
Hide Arm/Group Description:
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 396 397
Measure Type: Count of Participants
Unit of Measure: Participants
Non-SAEs
67
  16.9%
91
  22.9%
SAEs
147
  37.1%
124
  31.2%
38.Secondary Outcome
Title Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs
Hide Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented.
Time Frame Up to Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description:
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Overall Number of Participants Analyzed 173 174
Measure Type: Count of Participants
Unit of Measure: Participants
Non-SAEs
57
  32.9%
50
  28.7%
SAEs
90
  52.0%
90
  51.7%
Time Frame All-cause mortality, SAEs, and non-SAEs were collected up to Day 60 in Part 1 and 2 of the study
Adverse Event Reporting Description SAEs and non-serious AEs were reported for the Safety Population which comprised of all participants who received study intervention. All-cause mortality was reported for Enrolled population (all participants who entered the study). Sixteen participants from Enrolled Population (N=1156) did not receive study treatment, hence were not included in Safety Population (N=1140).
 
Arm/Group Title Part 1: Placebo 1 Part 1: Otilimab 90 mg Part 2: Placebo 2 Part 2: Otilimab 90 mg
Hide Arm/Group Description Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
All-Cause Mortality
Part 1: Placebo 1 Part 1: Otilimab 90 mg Part 2: Placebo 2 Part 2: Otilimab 90 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   93/403 (23.08%)      84/403 (20.84%)      76/175 (43.43%)      74/175 (42.29%)    
Hide Serious Adverse Events
Part 1: Placebo 1 Part 1: Otilimab 90 mg Part 2: Placebo 2 Part 2: Otilimab 90 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   147/396 (37.12%)      124/397 (31.23%)      90/173 (52.02%)      90/174 (51.72%)    
Blood and lymphatic system disorders         
Coagulopathy † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Cardiac disorders         
Cardiac arrest † 1  4/396 (1.01%)  4 8/397 (2.02%)  11 7/173 (4.05%)  9 4/174 (2.30%)  4
Cardio-respiratory arrest † 1  1/396 (0.25%)  1 2/397 (0.50%)  2 4/173 (2.31%)  4 7/174 (4.02%)  7
Atrial fibrillation † 1  3/396 (0.76%)  3 1/397 (0.25%)  1 2/173 (1.16%)  2 2/174 (1.15%)  2
Myocardial infarction † 1  0/396 (0.00%)  0 2/397 (0.50%)  2 1/173 (0.58%)  1 2/174 (1.15%)  2
Supraventricular tachycardia † 1  1/396 (0.25%)  2 0/397 (0.00%)  0 1/173 (0.58%)  1 1/174 (0.57%)  1
Bradycardia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Cardiac failure † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 1/173 (0.58%)  1 0/174 (0.00%)  0
Cardiogenic shock † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Cardiopulmonary failure † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Sinus node dysfunction † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Acute myocardial infarction † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Atrial flutter † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Cardiac failure congestive † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Cardiovascular insufficiency † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Left ventricular failure † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Myocarditis † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Paroxysmal atrioventricular block † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumopericardium † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pulseless electrical activity † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Right ventricular failure † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Gastrointestinal disorders         
Gastrointestinal haemorrhage † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Intestinal ischaemia † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Upper gastrointestinal haemorrhage † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Gastric ulcer † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Gastric ulcer haemorrhage † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Gastric varices haemorrhage † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Intestinal perforation † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Rectal ulcer haemorrhage † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Retroperitoneal haematoma † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Retroperitoneal haemorrhage † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Small intestinal obstruction † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
General disorders         
Multiple organ dysfunction syndrome † 1  15/396 (3.79%)  15 12/397 (3.02%)  12 8/173 (4.62%)  8 6/174 (3.45%)  6
Catheter site haemorrhage † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Chest pain † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Complication associated with device † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hyperthermia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Pyrexia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Systemic inflammatory response syndrome † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Hepatobiliary disorders         
Ischaemic hepatitis † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Acute hepatic failure † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Cholecystitis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Cholestasis † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Haemorrhagic cholecystitis † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hepatitis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Hepatitis fulminant † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hepatocellular injury † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Immune system disorders         
Haemophagocytic lymphohistiocytosis † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Infections and infestations         
Septic shock † 1  13/396 (3.28%)  14 14/397 (3.53%)  14 5/173 (2.89%)  5 8/174 (4.60%)  8
Pneumonia † 1  9/396 (2.27%)  9 7/397 (1.76%)  7 5/173 (2.89%)  5 6/174 (3.45%)  6
COVID-19 pneumonia † 1  3/396 (0.76%)  3 12/397 (3.02%)  12 4/173 (2.31%)  4 5/174 (2.87%)  5
COVID-19 † 1  5/396 (1.26%)  5 3/397 (0.76%)  3 9/173 (5.20%)  9 6/174 (3.45%)  6
Sepsis † 1  7/396 (1.77%)  7 1/397 (0.25%)  1 2/173 (1.16%)  2 4/174 (2.30%)  4
Pneumonia staphylococcal † 1  6/396 (1.52%)  6 1/397 (0.25%)  1 1/173 (0.58%)  1 4/174 (2.30%)  4
Pneumonia pseudomonal † 1  7/396 (1.77%)  7 2/397 (0.50%)  2 0/173 (0.00%)  0 0/174 (0.00%)  0
Klebsiella sepsis † 1  4/396 (1.01%)  4 1/397 (0.25%)  1 1/173 (0.58%)  1 2/174 (1.15%)  2
Staphylococcal bacteraemia † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 1/173 (0.58%)  1 4/174 (2.30%)  4
Staphylococcal sepsis † 1  2/396 (0.51%)  3 3/397 (0.76%)  3 0/173 (0.00%)  0 1/174 (0.57%)  1
Staphylococcal infection † 1  0/396 (0.00%)  0 4/397 (1.01%)  4 0/173 (0.00%)  0 1/174 (0.57%)  1
Bronchopulmonary aspergillosis † 1  3/396 (0.76%)  3 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Enterobacter pneumonia † 1  2/396 (0.51%)  3 1/397 (0.25%)  1 1/173 (0.58%)  1 0/174 (0.00%)  0
Pneumonia klebsiella † 1  2/396 (0.51%)  2 1/397 (0.25%)  1 1/173 (0.58%)  1 0/174 (0.00%)  0
Bacterial sepsis † 1  2/396 (0.51%)  2 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumonia bacterial † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Pneumonia haemophilus † 1  3/396 (0.76%)  5 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumonia serratia † 1  3/396 (0.76%)  3 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Urosepsis † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Acinetobacter infection † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Bacteraemia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Device related bacteraemia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Enterococcal infection † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Escherichia sepsis † 1  0/396 (0.00%)  0 2/397 (0.50%)  2 0/173 (0.00%)  0 0/174 (0.00%)  0
Lung abscess † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Pneumonia acinetobacter † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Pneumonia proteus † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Pneumonia streptococcal † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Pseudomonal bacteraemia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Pulmonary sepsis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 2/174 (1.15%)  2
Stenotrophomonas infection † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Tracheobronchitis bacterial † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Urinary tract infection † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Acinetobacter sepsis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Bacterial infection † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Candida pneumonia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Citrobacter infection † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Citrobacter sepsis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Clostridium difficile colitis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Coronavirus infection † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Device related sepsis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Diverticulitis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Enterobacter sepsis † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Fusobacterium infection † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Lactobacillus infection † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Mycetoma mycotic † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Oral candidiasis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Peritonitis † 1  1/396 (0.25%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumonia escherichia † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumonia pneumococcal † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pseudomembranous colitis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Serratia bacteraemia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Soft tissue infection † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Superinfection † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Tracheitis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Tracheobronchitis † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Urinary tract infection enterococcal † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Injury, poisoning and procedural complications         
Multiple injuries † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Subdural haematoma † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Tracheal injury † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Investigations         
Oxygen consumption increased † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Oxygen saturation decreased † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Haemoglobin decreased † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Liver function test abnormal † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Liver function test increased † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Pulmonary function test decreased † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Transaminases increased † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Troponin T increased † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Metabolism and nutrition disorders         
Failure to thrive † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 2/174 (1.15%)  2
Metabolic acidosis † 1  3/396 (0.76%)  3 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hypernatraemia † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Acidosis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Gout † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hypokalaemia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Lactic acidosis † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Haematoma muscle † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
B-cell lymphoma † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Oesophageal adenocarcinoma † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Nervous system disorders         
Ischaemic stroke † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 3/173 (1.73%)  3 0/174 (0.00%)  0
Cerebral haemorrhage † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 1/173 (0.58%)  1 0/174 (0.00%)  0
Intensive care unit acquired weakness † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 3/174 (1.72%)  3
Cerebrovascular accident † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 2/173 (1.16%)  2 0/174 (0.00%)  0
Encephalopathy † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Subarachnoid haemorrhage † 1  0/396 (0.00%)  0 2/397 (0.50%)  2 0/173 (0.00%)  0 0/174 (0.00%)  0
Haemorrhage intracranial † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Haemorrhagic stroke † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Hypercapnic coma † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Hypoxic-ischaemic encephalopathy † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Psychiatric disorders         
Organic brain syndrome † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury † 1  10/396 (2.53%)  11 9/397 (2.27%)  9 1/173 (0.58%)  1 6/174 (3.45%)  6
Oliguria † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Prerenal failure † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Renal failure † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Respiratory failure † 1  18/396 (4.55%)  18 17/397 (4.28%)  18 8/173 (4.62%)  8 6/174 (3.45%)  6
Acute respiratory failure † 1  10/396 (2.53%)  10 9/397 (2.27%)  9 9/173 (5.20%)  9 6/174 (3.45%)  6
Acute respiratory distress syndrome † 1  9/396 (2.27%)  9 11/397 (2.77%)  11 3/173 (1.73%)  3 3/174 (1.72%)  3
Hypoxia † 1  5/396 (1.26%)  5 5/397 (1.26%)  5 7/173 (4.05%)  7 4/174 (2.30%)  4
Pneumothorax † 1  9/396 (2.27%)  10 8/397 (2.02%)  8 1/173 (0.58%)  1 3/174 (1.72%)  3
Pulmonary embolism † 1  11/396 (2.78%)  11 6/397 (1.51%)  6 3/173 (1.73%)  3 1/174 (0.57%)  1
Respiratory distress † 1  2/396 (0.51%)  2 2/397 (0.50%)  2 5/173 (2.89%)  5 5/174 (2.87%)  5
Respiratory disorder † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 3/173 (1.73%)  3 3/174 (1.72%)  3
Pneumomediastinum † 1  3/396 (0.76%)  3 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Organising pneumonia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 2/174 (1.15%)  2
Pulmonary fibrosis † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 1/173 (0.58%)  1 0/174 (0.00%)  0
Dyspnoea † 1  1/396 (0.25%)  1 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Interstitial lung disease † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Laryngeal oedema † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pleural effusion † 1  2/396 (0.51%)  2 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumothorax spontaneous † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 1/174 (0.57%)  1
Acute pulmonary oedema † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Bronchospasm † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Haemothorax † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Hypercapnia † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Pneumonia aspiration † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 0/173 (0.00%)  0 1/174 (0.57%)  1
Pulmonary oedema † 1  0/396 (0.00%)  0 0/397 (0.00%)  0 1/173 (0.58%)  1 0/174 (0.00%)  0
Respiratory arrest † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Stridor † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Tachypnoea † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Vocal cord dysfunction † 1  0/396 (0.00%)  0 1/397 (0.25%)  1 0/173 (0.00%)  0 0/174 (0.00%)  0
Skin and subcutaneous tissue disorders         
Rash † 1  1/396 (0.25%)  1 0/397 (0.00%)  0 0/173 (0.00%)  0 0/174 (0.00%)  0
Subcutaneous emphysema † 1  1/396 (0.25%)  1