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Clinical Trial Results:
A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab in patients with severe pulmonary COVID-19 related disease

Summary
EudraCT number	2020-001759-42
Trial protocol	GB NL ES BE DE IT
Global end of trial date	16 Aug 2021

Results information
Results version number	v1(current)
This version publication date	16 Mar 2022
First version publication date	16 Mar 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

214094

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

24 Sep 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Aug 2021

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of otilimab intravenous (IV) versus placebo

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

28 May 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 102

Country: Number of subjects enrolled

Belgium: 21

Country: Number of subjects enrolled

Brazil: 31

Country: Number of subjects enrolled

Canada: 19

Country: Number of subjects enrolled

Chile: 11

Country: Number of subjects enrolled

Colombia: 1

Country: Number of subjects enrolled

France: 258

Country: Number of subjects enrolled

India: 72

Country: Number of subjects enrolled

Italy: 7

Country: Number of subjects enrolled

Japan: 48

Country: Number of subjects enrolled

Mexico: 48

Country: Number of subjects enrolled

Netherlands: 47

Country: Number of subjects enrolled

Peru: 12

Country: Number of subjects enrolled

Poland: 12

Country: Number of subjects enrolled

Russian Federation: 113

Country: Number of subjects enrolled

South Africa: 36

Country: Number of subjects enrolled

Spain: 94

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

United States: 214

Worldwide total number of subjects

1156

EEA total number of subjects

439

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

499

From 65 to 84 years

643

85 years and over

Subject disposition

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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.

Screening 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).

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Part 1: Placebo 1

Arm 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.

Arm type

Placebo

Investigational medicinal product name

Placebo 1

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Sterile 0.9% (w/v) sodium chloride solution administered once via IV infusion

Part 1: Otilimab 90 mg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Otilimab 90 mg (diluted in sodium chloride solution)

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Solution in single-use vial (150 mg/milliliters [mL]) diluted in sterile 0.9% (w/v) sodium chloride solution and administered once via IV infusion

Part 2: Placebo 2

Arm 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.

Arm type

Placebo

Investigational medicinal product name

Placebo 2

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Sterile 5% (w/v) dextrose solution administered once via IV infusion

Part 2: Otilimab 90 mg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Otilimab 90 mg (diluted in dextrose solution)

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Solution in single-use vial (150 mg/mL) diluted in sterile 5% (w/v) dextrose solution and administered once via IV infusion

Number of subjects in period 1	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Started	403	403	175	175
Completed	388	379	170	171
Not completed	15	24	5	4
Consent withdrawn by subject	7	8	1	1
Physician decision	2	5	1	1
Lost to follow-up	4	8	3	2
Protocol deviation	2	3	-	-

Baseline characteristics

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Reporting group title

Part 1: Placebo 1

Reporting group description

Reporting group title

Part 1: Otilimab 90 mg

Reporting group description

Reporting group title

Part 2: Placebo 2

Reporting 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.

Reporting group title

Part 2: Otilimab 90 mg

Reporting group description

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.

Reporting group values	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg	Total
Number of subjects	403	403	175	175	1156
Age Categorical
Baseline characteristics were presented for Enrolled Population.
Units: Participants
<18 years	0	0	0	0	0
Between 18 to 64 years	249	250	0	0	499
>=65 to 84 years	154	153	168	168	643
>=85 years	0	0	7	7	14
Age continuous
Baseline characteristics were presented for Enrolled Population.
Units: years
arithmetic mean (standard deviation)	59.4 ± 11.86	59.8 ± 11.69	75.0 ± 4.67	75.3 ± 4.70	-
Sex: Female, Male
Baseline characteristics were presented for Enrolled Population.
Units: Participants
Female	128	101	75	73	377
Male	275	302	100	102	779
Race/Ethnicity, Customized
Baseline characteristics were presented for Enrolled Population.
Units: Subjects
American Indian or Alaska Native	24	30	3	8	65
Asian - Central/South Asian Heritage	42	31	1	0	74
Asian - East Asian Heritage	4	4	0	0	8
Asian - Japanese Heritage	15	14	13	5	47
Asian - South East Asian Heritage	12	8	1	0	21
Black or African American	25	26	6	6	63
White - Arabic/North African Heritage	27	21	14	21	83
White - White/Caucasian/European Heritage	235	251	136	134	756
Mixed Asian Race	0	1	0	0	1
Mixed White Race	1	1	1	0	3
Multiple	7	7	0	0	14
Unknown	11	9	0	1	21

End points

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Reporting group title

Part 1: Placebo 1

Reporting group description

Reporting group title

Part 1: Otilimab 90 mg

Reporting group description

Reporting group title

Part 2: Placebo 2

Reporting 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.

Reporting group title

Part 2: Otilimab 90 mg

Reporting group description

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.

Primary: Part 1: Percentage of participants alive and free of respiratory failure at Day 28

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End point title

Part 1: Percentage of participants alive and free of respiratory failure at Day 28 ^[1]

End point description

Participants were considered alive and free of respiratory failure if they were in category 1,2,3 or 4 from the 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/nasal prongs;5) Hospitalized,highflow oxygen (>=15 liters per minute),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 indicate higher intensity of respiratory failure. Percentage values are rounded off.Modified intent to treat(mITT) population consisted of all randomized participants who received study intervention.Only those participants with data available at specified timepoints were analyzed

End point type

Primary

End point timeframe

At Day 28

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	393 ^[2]	389 ^[3]
Units: Percentage of participants	67	71

Notes
[2] - mITT Population
[3] - mITT Population

Statistical analysis 1

Statistical analysis description

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.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

782

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0456 ^[4]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.82

Notes
[4] - p-value is from a one-sided test.

Primary: Part 2: Percentage of participants alive and free of respiratory failure at Day 28

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End point title

Part 2: Percentage of participants alive and free of respiratory failure at Day 28 ^[5]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Primary

End point timeframe

At Day 28

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[6]	172 ^[7]
Units: Percentage of participants	51	52

Notes
[6] - mITT Population.
[7] - mITT Population.

Statistical analysis 1

Statistical analysis description

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.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8574 ^[8]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.61

Notes
[8] - p-value is generated from a two-sided test.

Secondary: Part 1: Number of participants who died due to all causes at Day 60

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End point title

Part 1: Number of participants who died due to all causes at Day 60 ^[9]

End point description

Number of participants who died due to all causes at Day 60 are reported. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 60

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	386 ^[10]	373 ^[11]
Units: Participants	93	84

Notes
[10] - mITT Population.
[11] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

759

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2057 ^[12]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.22

Notes
[12] - p-value is from a one-sided test.

Secondary: Part 2: Number of participants who died due to all causes at Day 28

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End point title

Part 2: Number of participants who died due to all causes at Day 28 ^[13]

End point description

Number of participants who died due to all causes at Day 28 is reported. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 28

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[14]	172 ^[15]
Units: Participants	70	63

Notes
[14] - mITT Population.
[15] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3061 ^[16]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.24

Notes
[16] - p-value is generated from a two-sided test.

Secondary: Part 2: Number of participants who died due to all causes at Day 60

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End point title

Part 2: Number of participants who died due to all causes at Day 60 ^[17]

End point description

Number of participants who died due to all causes at Day 60 is reported. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 60

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[18]	171 ^[19]
Units: Participants	76	74

Notes
[18] - mITT Population.
[19] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6665 ^[20]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.41

Notes
[20] - p-value is generated from a two-sided test.

Secondary: Part 1: Time to death due to all causes up to Day 60

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End point title

Part 1: Time to death due to all causes up to Day 60 ^[21]

End point 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. Only those participants with data available at the specified time points were analyzed. 9999 indicates that <25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	93 ^[22]	84 ^[23]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (99999 to 99999)	99999 (99999 to 99999)

Notes
[22] - mITT Population.
[23] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1942 ^[24]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.18

Notes
[24] - p-value is from a one-sided test.

Secondary: Part 2: Time to death due to all causes up to Day 60

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End point title

Part 2: Time to death due to all causes up to Day 60 ^[25]

End point 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. Only those participants with data available at the specified time points were analyzed. 9999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	76 ^[26]	74 ^[27]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (16 to 99999)	99999 (16 to 99999)

Notes
[26] - mITT Population.
[27] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5324 ^[28]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.24

Notes
[28] - p-value is generated from a two-sided test

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 7

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End point title

Part 1: Percentage of participants alive and free of respiratory failure at Day 7 ^[29]

End point description

End point type

Secondary

End point timeframe

At Day 7

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	396 ^[30]	393 ^[31]
Units: Percentage of participants	42	44

Notes
[30] - mITT Population.
[31] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

789

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2871 ^[32]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.49

Notes
[32] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 14

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End point title

Part 1: Percentage of participants alive and free of respiratory failure at Day 14 ^[33]

End point description

End point type

Secondary

End point timeframe

At Day 14

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	394 ^[34]	391 ^[35]
Units: Percentage of participants	61	63

Notes
[34] - mITT Population.
[35] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

785

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1754 ^[36]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.58

Notes
[36] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 60

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End point title

Part 1: Percentage of participants alive and free of respiratory failure at Day 60 ^[37]

End point description

End point type

Secondary

End point timeframe

At Day 60

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	386 ^[38]	373 ^[39]
Units: Percentage of participants	74	75

Notes
[38] - mITT Population.
[39] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

759

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.183 ^[40]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.63

Notes
[40] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 42

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End point title

Part 1: Percentage of participants alive and free of respiratory failure at Day 42 ^[41]

End point description

End point type

Secondary

End point timeframe

At Day 42

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	392 ^[42]	385 ^[43]
Units: Percentage of participants	70	74

Notes
[42] - mITT Population.
[43] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

777

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0616 ^[44]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

1.79

Notes
[44] - p-value is from a one-sided test.

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 7

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End point title

Part 2: Percentage of participants alive and free of respiratory failure at Day 7 ^[45]

End point description

End point type

Secondary

End point timeframe

At Day 7

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	173 ^[46]	174 ^[47]
Units: Percentage of participants	28	37

Notes
[46] - mITT Population.
[47] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

347

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0831 ^[48]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.39

Notes
[48] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 14

Top of page

End point title

Part 2: Percentage of participants alive and free of respiratory failure at Day 14 ^[49]

End point description

End point type

Secondary

End point timeframe

At Day 14

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	171 ^[50]	174 ^[51]
Units: Percentage of participants	43	49

Notes
[50] - mITT Population.
[51] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2557 ^[52]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

Notes
[52] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 42

Top of page

End point title

Part 2: Percentage of participants alive and free of respiratory failure at Day 42 ^[53]

End point description

End point type

Secondary

End point timeframe

At Day 42

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[54]	172 ^[55]
Units: Percentage of participants	54	54

Notes
[54] - mITT Population.
[55] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.856 ^[56]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.61

Notes
[56] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 60

Top of page

End point title

Part 2: Percentage of participants alive and free of respiratory failure at Day 60 ^[57]

End point description

End point type

Secondary

End point timeframe

At Day 60

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[58]	171 ^[59]
Units: Percentage of participants	55	56

Notes
[58] - mITT Population
[59] - mITT Population

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7533 ^[60]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.66

Notes
[60] - p-value is generated from a two-sided test.

Secondary: Part 1: Time to recovery from respiratory failure up to Day 28

Top of page

End point title

Part 1: Time to recovery from respiratory failure up to Day 28 ^[61]

End point description

Time to recovery from respiratory failure was defined as time (days) from dosing to last recovery from respiratory failure upto (and including) Day 28.Participants were in respiratory failure if they were in category 5 or above from the GSK modified ordinal scale adapted from 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/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.9999 indicates that <75% participants experienced event within treatment arm. Third-quartile could not be derived. Only those participants with data available at the specified time points were analyzed

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	263 ^[62]	281 ^[63]
Units: Days
median (inter-quartile range (Q1-Q3))	10 (5 to 99999)	9 (5 to 99999)

Notes
[62] - mITT Population.
[63] - mITT Population

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0959 ^[64]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.32

Notes
[64] - p-value is from a one-sided test.

Secondary: Part 2: Time to recovery from respiratory failure up to Day 28

Top of page

End point title

Part 2: Time to recovery from respiratory failure up to Day 28 ^[65]

End point description

Time to recovery from respiratory failure was defined as time (days) from dosing to last recovery from respiratory failure upto (and including) Day 28.Participants were in respiratory failure if they were in category 5 or above from the GSK modified ordinal scale adapted from 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/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.99999 indicates that <75% participants experienced event within treatment arm. Third-quartile could not be derived. Only those participants with data available at the specified time points were analyzed

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	90 ^[66]	91 ^[67]
Units: Days
median (inter-quartile range (Q1-Q3))	24 (7 to 99999)	22 (5 to 99999)

Notes
[66] - mITT Population
[67] - mITT Population

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4421 ^[68]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.5

Notes
[68] - p-value is generated from a two-sided test.

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 7

Top of page

End point title

Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 7 ^[69]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 7

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	396 ^[70]	393 ^[71]
Units: Percentage of participants	11	12

Notes
[70] - mITT Population.
[71] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

789

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2814 ^[72]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.8

Notes
[72] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 14

Top of page

End point title

Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 14 ^[73]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 14

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	394 ^[74]	391 ^[75]
Units: Percentage of participants	37	37

Notes
[74] - mITT Population.
[75] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

785

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3901 ^[76]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.42

Notes
[76] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 28

Top of page

End point title

Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 28 ^[77]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 28

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	393 ^[78]	389 ^[79]
Units: Percentage of participants	57	57

Notes
[78] - mITT Population.
[79] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

782

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4763 ^[80]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.36

Notes
[80] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 42

Top of page

End point title

Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 42 ^[81]

End point 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. Only those participants with data available at the specified time points were analyzed. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 42

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	392 ^[82]	385 ^[83]
Units: Percentage of participants	63	66

Notes
[82] - mITT population.
[83] - mITT population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

777

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1973 ^[84]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.56

Notes
[84] - p-value is from a one-sided test.

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 60

Top of page

End point title

Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 60 ^[85]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 60

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	386 ^[86]	373 ^[87]
Units: Percentage of participants	67	71

Notes
[86] - mITT Population.
[87] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

759

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1173 ^[88]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.67

Notes
[88] - p-value is from a one-sided test.

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 7

Top of page

End point title

Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 7 ^[89]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 7

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	173 ^[90]	174 ^[91]
Units: Percentage of participants	3	13

Notes
[90] - mITT Population.
[91] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

347

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0037 ^[92]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.98

Confidence interval

level

95%

sides

2-sided

lower limit

1.57

upper limit

10.13

Notes
[92] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 14

Top of page

End point title

Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 14 ^[93]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 14

Notes
[93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	171 ^[94]	174 ^[95]
Units: Percentage of participants	23	28

Notes
[94] - mITT Population.
[95] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3581 ^[96]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

2.06

Notes
[96] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 28

Top of page

End point title

Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 28 ^[97]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 28

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[98]	172 ^[99]
Units: Percentage of participants	39	38

Notes
[98] - mITT Population.
[99] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9621 ^[100]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.54

Notes
[100] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 42

Top of page

End point title

Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 42 ^[101]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 42

Notes
[101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[102]	172 ^[103]
Units: Percentage of participants	46	41

Notes
[102] - mITT Population.
[103] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

342

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4167 ^[104]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.29

Notes
[104] - p-value is generated from a two-sided test.

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 60

Top of page

End point title

Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 60 ^[105]

End point 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. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At Day 60

Notes
[105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	170 ^[106]	171 ^[107]
Units: Percentage of participants	51	46

Notes
[106] - mITT Population.
[107] - mITT Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

341

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3408 ^[108]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.25

Notes
[108] - p-value is generated from a two-sided test.

Secondary: Part 1: Time to last dependence on supplementary oxygen

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End point title

Part 1: Time to last dependence on supplementary oxygen ^[109]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	223 ^[110]	221 ^[111]
Units: Days
median (inter-quartile range (Q1-Q3))	22 (11 to 99999)	21 (10 to 99999)

Notes
[110] - mITT Population.
[111] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

444

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.425 ^[112]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.23

Notes
[112] - p-value is from a one-sided test.

Secondary: Part 2: Time to last dependence on supplementary oxygen

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End point title

Part 2: Time to last dependence on supplementary oxygen ^[113]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[113] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	66 ^[114]	68 ^[115]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (15 to 99999)	99999 (13 to 99999)

Notes
[114] - mITT Population.
[115] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4774 ^[116]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.59

Notes
[116] - p-value is generated from a two-sided test.

Secondary: Part 1: Percentage of participants admitted to Intensive Care Unit (ICU) up to Day 28

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End point title

Part 1: Percentage of participants admitted to Intensive Care Unit (ICU) up to Day 28 ^[117]

End point description

Participants who were admitted to the ICU up to (and including) Day 28 were evaluated. Percentage values are rounded off. 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.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[117] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	98 ^[118]	95 ^[119]
Units: Percentage of participants	24	13

Notes
[118] - mITT Population (not in ICU at Baseline)
[119] - mITT Population (not in ICU at Baseline)

Statistical analysis 1

Statistical analysis description

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

193

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0119 ^[120]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.18

upper limit

0.89

Notes
[120] - p-value is from a one-sided test.

Secondary: Part 1: Time to final ICU discharge

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End point title

Part 1: Time to final ICU discharge ^[121]

End point 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. mITT Population admitted to ICU at Baseline comprised of those participants in mITT who were admitted to ICU at Baseline. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[121] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	300 ^[122]	300 ^[123]
Units: Days
median (inter-quartile range (Q1-Q3))	13 (7 to 99999)	15 (7 to 99999)

Notes
[122] - mITT population admitted to ICU at Baseline.
[123] - mITT population admitted to ICU at Baseline.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4404 ^[124]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.24

Notes
[124] - p-value is from a one-sided test.

Secondary: Part 2: Time to final ICU discharge

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End point title

Part 2: Time to final ICU discharge ^[125]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	38 ^[126]	44 ^[127]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (12 to 99999)	99999 (7 to 99999)

Notes
[126] - mITT population admitted to ICU at Baseline.
[127] - mITT population admitted to ICU at Baseline.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6253 ^[128]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.72

Notes
[128] - p-value is generated from a two-sided test.

Secondary: Part 1: Time to first discharge from investigator site up to Day 60

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End point title

Part 1: Time to first discharge from investigator site up to Day 60 ^[129]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	288 ^[130]	294 ^[131]
Units: Days
median (inter-quartile range (Q1-Q3))	18 (11 to 99999)	18 (10 to 99999)

Notes
[130] - mITT Population.
[131] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

582

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1078 ^[132]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.3

Notes
[132] - p-value is from a one-sided test.

Secondary: Part 1: Time to first discharge to non-hospitalized residence up to Day 60

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End point title

Part 1: Time to first discharge to non-hospitalized residence up to Day 60 ^[133]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[133] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	269 ^[134]	280 ^[135]
Units: Days
median (inter-quartile range (Q1-Q3))	21 (12 to 99999)	20 (11 to 99999)

Notes
[134] - mITT Population.
[135] - mITT Population.

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

Comparison groups

Part 1: Placebo 1 v Part 1: Otilimab 90 mg

Number of subjects included in analysis

549

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.114 ^[136]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.31

Notes
[136] - p-value is from a one-sided test.

Secondary: Part 2: Time to first discharge from investigator site up to Day 60

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End point title

Part 2: Time to first discharge from investigator site up to Day 60 ^[137]

End point 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. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	96 ^[138]	99 ^[139]
Units: Days
median (inter-quartile range (Q1-Q3))	36 (15 to 99999)	37 (15 to 99999)

Notes
[138] - mITT Population.
[139] - mITT Population.

Statistical analysis 1

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other ^[140]

P-value

= 0.7084 ^[141]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.4

Notes
[140] - Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
[141] - p-value is generated from a two-sided test.

Secondary: Part 2: Time to first discharge to non-hospitalized residence

Top of page

End point title

Part 2: Time to first discharge to non-hospitalized residence ^[142]

End point description

Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant (parti) was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Only those participants with data available at the specified time points were analyzed. In Part 2: Placebo 2 arm, 99999 indicates that <50% participants experienced event within treatment arm. Hence, median and third-quartile could not be derived. In Part 2: Otilimab 90 mg arm, 99999 indicates that <75%participants experienced event within the treatment arm. Hence, third-quartile could not be derived.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	86 ^[143]	90 ^[144]
Units: Days
median (inter-quartile range (Q1-Q3))	99999 (18 to 99999)	53 (15 to 99999)

Notes
[143] - mITT Population
[144] - mITT Population

Statistical analysis 1

Statistical analysis description

Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

Comparison groups

Part 2: Placebo 2 v Part 2: Otilimab 90 mg

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4085 ^[145]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.52

Notes
[145] - p-value is generated from a two-sided test.

Secondary: Part 1: Number of participants with serious adverse events (SAEs) and common (>=5%) non-serious adverse events (non-SAEs)

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End point title

Part 1: Number of participants with serious adverse events (SAEs) and common (>=5%) non-serious adverse events (non-SAEs) ^[146]

End point 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. Safety population comprised of all participants who received study intervention.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Number of subjects analysed	396 ^[147]	397 ^[148]
Units: Participants
Non-SAEs	67	91
SAEs	147	124

Notes
[147] - Safety Population
[148] - Safety Population

No statistical analyses for this end point

Secondary: Part 2: Number of participants with SAEs and common (>=5%) non-SAEs

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End point title

Part 2: Number of participants with SAEs and common (>=5%) non-SAEs ^[149]

End point 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.

End point type

Secondary

End point timeframe

Up to Day 60

Notes
[149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study.

End point values	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Number of subjects analysed	173 ^[150]	174 ^[151]
Units: Participants
Non-SAEs	57	50
SAEs	90	90

Notes
[150] - Safety Population
[151] - Safety Population

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

All-cause mortality, SAEs, and non-SAEs were collected up to Day 60 in Part 1 and 2 of the study

Adverse event reporting additional description

SAEs and non-serious AEs were reported for Safety Population (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)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Part 1: Placebo 1

Reporting group description

Reporting group title

Part 1: Otilimab 90 mg

Reporting group description

Reporting group title

Part 2: Placebo 2

Reporting 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.

Reporting group title

Part 2: Otilimab 90 mg

Reporting group description

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.

Serious adverse events	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Total subjects affected by serious adverse events
subjects affected / exposed	147 / 396 (37.12%)	124 / 397 (31.23%)	90 / 173 (52.02%)	90 / 174 (51.72%)
number of deaths (all causes)	93	84	76	74
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal adenocarcinoma
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Shock
subjects affected / exposed	4 / 396 (1.01%)	0 / 397 (0.00%)	3 / 173 (1.73%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	1 / 4	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 0	0 / 3	0 / 2
Hypotension
subjects affected / exposed	3 / 396 (0.76%)	1 / 397 (0.25%)	2 / 173 (1.16%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Deep vein thrombosis
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	2 / 173 (1.16%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	5 / 396 (1.26%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Embolism
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arterial haemorrhage
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Multiple organ dysfunction syndrome
subjects affected / exposed	15 / 396 (3.79%)	12 / 397 (3.02%)	8 / 173 (4.62%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	0 / 15	1 / 12	1 / 8	0 / 6
deaths causally related to treatment / all	0 / 15	1 / 10	1 / 8	0 / 6
Catheter site haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Complication associated with device
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Immune system disorders
Haemophagocytic lymphohistiocytosis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Homeless
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory failure
subjects affected / exposed	18 / 396 (4.55%)	17 / 397 (4.28%)	8 / 173 (4.62%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	0 / 18	0 / 18	0 / 8	0 / 6
deaths causally related to treatment / all	0 / 14	0 / 13	0 / 7	0 / 6
Acute respiratory failure
subjects affected / exposed	10 / 396 (2.53%)	9 / 397 (2.27%)	9 / 173 (5.20%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	0 / 10	1 / 9	0 / 9	0 / 6
deaths causally related to treatment / all	0 / 5	1 / 7	0 / 7	0 / 6
Acute respiratory distress syndrome
subjects affected / exposed	9 / 396 (2.27%)	11 / 397 (2.77%)	3 / 173 (1.73%)	3 / 174 (1.72%)
occurrences causally related to treatment / all	1 / 9	0 / 11	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 8	0 / 8	0 / 2	0 / 3
Hypoxia
subjects affected / exposed	5 / 396 (1.26%)	5 / 397 (1.26%)	7 / 173 (4.05%)	4 / 174 (2.30%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 7	0 / 4
deaths causally related to treatment / all	0 / 3	0 / 4	0 / 7	0 / 4
Pneumothorax
subjects affected / exposed	9 / 396 (2.27%)	8 / 397 (2.02%)	1 / 173 (0.58%)	3 / 174 (1.72%)
occurrences causally related to treatment / all	0 / 10	0 / 8	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 2	0 / 3	0 / 0	0 / 1
Pulmonary embolism
subjects affected / exposed	11 / 396 (2.78%)	6 / 397 (1.51%)	3 / 173 (1.73%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 11	0 / 6	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
Respiratory distress
subjects affected / exposed	2 / 396 (0.51%)	2 / 397 (0.50%)	5 / 173 (2.89%)	5 / 174 (2.87%)
occurrences causally related to treatment / all	0 / 2	2 / 2	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 1	2 / 2	0 / 4	0 / 5
Respiratory disorder
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	3 / 173 (1.73%)	3 / 174 (1.72%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 3
Pneumomediastinum
subjects affected / exposed	3 / 396 (0.76%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Organising pneumonia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Dyspnoea
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal oedema
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute pulmonary oedema
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Bronchospasm
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercapnia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pulmonary oedema
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Respiratory arrest
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Stridor
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachypnoea
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord dysfunction
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Organic brain syndrome
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Oxygen consumption increased
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Oxygen saturation decreased
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary function test decreased
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Troponin T increased
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Multiple injuries
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tracheal injury
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	4 / 396 (1.01%)	8 / 397 (2.02%)	7 / 173 (4.05%)	4 / 174 (2.30%)
occurrences causally related to treatment / all	1 / 4	0 / 11	0 / 9	0 / 4
deaths causally related to treatment / all	1 / 2	0 / 6	0 / 6	0 / 3
Cardio-respiratory arrest
subjects affected / exposed	1 / 396 (0.25%)	2 / 397 (0.50%)	4 / 173 (2.31%)	7 / 174 (4.02%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 5
Atrial fibrillation
subjects affected / exposed	3 / 396 (0.76%)	1 / 397 (0.25%)	2 / 173 (1.16%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Myocardial infarction
subjects affected / exposed	0 / 396 (0.00%)	2 / 397 (0.50%)	1 / 173 (0.58%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
Supraventricular tachycardia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	1 / 173 (0.58%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
Cardiogenic shock
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Cardiopulmonary failure
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Cardiovascular insufficiency
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Left ventricular failure
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paroxysmal atrioventricular block
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumopericardium
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulseless electrical activity
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Right ventricular failure
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Nervous system disorders
Ischaemic stroke
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	3 / 173 (1.73%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Intensive care unit acquired weakness
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	3 / 174 (1.72%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	2 / 173 (1.16%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
Encephalopathy
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Subarachnoid haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	2 / 397 (0.50%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Hypercapnic coma
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Coagulopathy
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric varices haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Rectal ulcer haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retroperitoneal haematoma
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retroperitoneal haemorrhage
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Ischaemic hepatitis
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Acute hepatic failure
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhagic cholecystitis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis fulminant
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Hepatocellular injury
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous emphysema
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Toxic epidermal necrolysis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	10 / 396 (2.53%)	9 / 397 (2.27%)	1 / 173 (0.58%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	0 / 11	1 / 9	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 2
Oliguria
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prerenal failure
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Haematoma muscle
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Septic shock
subjects affected / exposed	13 / 396 (3.28%)	14 / 397 (3.53%)	5 / 173 (2.89%)	8 / 174 (4.60%)
occurrences causally related to treatment / all	2 / 14	4 / 14	1 / 5	0 / 8
deaths causally related to treatment / all	0 / 5	4 / 9	1 / 3	0 / 6
Pneumonia
subjects affected / exposed	9 / 396 (2.27%)	7 / 397 (1.76%)	5 / 173 (2.89%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	3 / 9	3 / 7	1 / 5	0 / 6
deaths causally related to treatment / all	0 / 2	1 / 3	1 / 3	0 / 3
COVID-19 pneumonia
subjects affected / exposed	3 / 396 (0.76%)	12 / 397 (3.02%)	4 / 173 (2.31%)	5 / 174 (2.87%)
occurrences causally related to treatment / all	0 / 3	1 / 12	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 3	1 / 11	0 / 3	0 / 5
COVID-19
subjects affected / exposed	5 / 396 (1.26%)	3 / 397 (0.76%)	9 / 173 (5.20%)	6 / 174 (3.45%)
occurrences causally related to treatment / all	0 / 5	0 / 3	0 / 9	0 / 6
deaths causally related to treatment / all	0 / 5	0 / 2	0 / 9	0 / 6
Sepsis
subjects affected / exposed	7 / 396 (1.77%)	1 / 397 (0.25%)	2 / 173 (1.16%)	4 / 174 (2.30%)
occurrences causally related to treatment / all	2 / 7	0 / 1	0 / 2	0 / 4
deaths causally related to treatment / all	1 / 5	0 / 1	0 / 2	0 / 3
Pneumonia staphylococcal
subjects affected / exposed	6 / 396 (1.52%)	1 / 397 (0.25%)	1 / 173 (0.58%)	4 / 174 (2.30%)
occurrences causally related to treatment / all	2 / 6	1 / 1	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	7 / 396 (1.77%)	2 / 397 (0.50%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 7	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	1 / 2	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	4 / 396 (1.01%)	1 / 397 (0.25%)	1 / 173 (0.58%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	2 / 4	0 / 1	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 1
Staphylococcal bacteraemia
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	1 / 173 (0.58%)	4 / 174 (2.30%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
Staphylococcal sepsis
subjects affected / exposed	2 / 396 (0.51%)	3 / 397 (0.76%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 396 (0.00%)	4 / 397 (1.01%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
Bronchopulmonary aspergillosis
subjects affected / exposed	3 / 396 (0.76%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Enterobacter pneumonia
subjects affected / exposed	2 / 396 (0.51%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia klebsiella
subjects affected / exposed	2 / 396 (0.51%)	1 / 397 (0.25%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Bacterial sepsis
subjects affected / exposed	2 / 396 (0.51%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Pneumonia haemophilus
subjects affected / exposed	3 / 396 (0.76%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia serratia
subjects affected / exposed	3 / 396 (0.76%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 396 (0.51%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1
Acinetobacter infection
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related bacteraemia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Enterococcal infection
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 396 (0.00%)	2 / 397 (0.50%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Pneumonia acinetobacter
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pneumonia proteus
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia streptococcal
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomonal bacteraemia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
Stenotrophomonas infection
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Tracheobronchitis bacterial
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acinetobacter sepsis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Candida pneumonia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Citrobacter infection
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Citrobacter sepsis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus infection
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterobacter sepsis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Fusobacterium infection
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Lactobacillus infection
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mycetoma mycotic
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
Oral candidiasis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia escherichia
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Pseudomembranous colitis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Serratia bacteraemia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Superinfection
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tracheobronchitis
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	0 / 173 (0.00%)	1 / 174 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Urinary tract infection enterococcal
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	0 / 396 (0.00%)	0 / 397 (0.00%)	1 / 173 (0.58%)	2 / 174 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
Metabolic acidosis
subjects affected / exposed	3 / 396 (0.76%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypernatraemia
subjects affected / exposed	1 / 396 (0.25%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acidosis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Gout
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 396 (0.25%)	0 / 397 (0.00%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lactic acidosis
subjects affected / exposed	0 / 396 (0.00%)	1 / 397 (0.25%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	97 / 396 (24.49%)	115 / 397 (28.97%)	57 / 173 (32.95%)	51 / 174 (29.31%)
Vascular disorders
Hypotension
subjects affected / exposed	13 / 396 (3.28%)	13 / 397 (3.27%)	11 / 173 (6.36%)	9 / 174 (5.17%)
occurrences all number	17	14	13	11
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	15 / 396 (3.79%)	11 / 397 (2.77%)	10 / 173 (5.78%)	7 / 174 (4.02%)
occurrences all number	15	13	11	7
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	22 / 396 (5.56%)	18 / 397 (4.53%)	10 / 173 (5.78%)	11 / 174 (6.32%)
occurrences all number	22	19	10	11
Gastrointestinal disorders
Constipation
subjects affected / exposed	35 / 396 (8.84%)	39 / 397 (9.82%)	15 / 173 (8.67%)	16 / 174 (9.20%)
occurrences all number	35	42	16	16
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	17 / 396 (4.29%)	15 / 397 (3.78%)	11 / 173 (6.36%)	8 / 174 (4.60%)
occurrences all number	18	16	13	9
Infections and infestations
Pneumonia
subjects affected / exposed	21 / 396 (5.30%)	37 / 397 (9.32%)	12 / 173 (6.94%)	6 / 174 (3.45%)
occurrences all number	21	43	12	7
Urinary tract infection
subjects affected / exposed	13 / 396 (3.28%)	12 / 397 (3.02%)	10 / 173 (5.78%)	5 / 174 (2.87%)
occurrences all number	13	13	10	5
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	14 / 396 (3.54%)	12 / 397 (3.02%)	4 / 173 (2.31%)	10 / 174 (5.75%)
occurrences all number	15	13	5	14
Hypernatraemia
subjects affected / exposed	9 / 396 (2.27%)	20 / 397 (5.04%)	0 / 173 (0.00%)	0 / 174 (0.00%)
occurrences all number	9	22	0	0
Fluid overload
subjects affected / exposed	2 / 396 (0.51%)	1 / 397 (0.25%)	5 / 173 (2.89%)	9 / 174 (5.17%)
occurrences all number	2	1	5	10

More information

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Were there any global substantial amendments to the protocol? Yes

18 May 2020

Amendment 1: Modifications to the protocol in response to regulatory feedback, and clarifications based on investigator feedback. The key change is revision of the primary endpoint (where definition of “free of respiratory failure” is participants in categories 1-4 on GlaxoSmithKline [GSK] Ordinal Scale). Other changes are (1) to revise recording of blood pressure and pulse rate; (2) to add details of randomization caps; (3) to simplify/clarify some Inclusion and Exclusion Criteria; (4) to clarify medications permitted during the study.

02 Jul 2020

Amendment 2: Modifications to the protocol in response to regulatory and ethics committee feedback, and clarifications based on investigator feedback. The main changes are (1) clarification that Day 1 pre-dose assessments do not need to be repeated if Screening and Randomization are within 24 hours; (2) expedited reporting of cytokine release syndrome (CRS) as an adverse event of special interest (AESI); (3) clarification that organ transplant participants are excluded per Exclusion Criteria #11; (4) clarification of conditions by which convalescent plasma is permitted or not during the study; (5) removed specific mention of chloroquine and hydroxychloroquine; (6) expanded the null hypothesis; (7) consent may be collected before the 48hour screening window.

25 Jan 2021

Amendment 3: Before the last of 806 participants completed the study (Last Subject Last Visit, Day 60), an interim analysis of the primary endpoint and all-cause mortality data at Day 28 showed that substantial clinical benefit was evident in one of the pre-defined stratification subgroups “Age 70 to less than (<)80 years”, with no safety concerns in any subgroup. Given the ongoing pandemic and particularly high mortality of Coronavirus Disease-2019 (COVID-19) disease in participants over 70 years old, together with recent publications that support the hypothesis that the severity of the disease is driven by a maladaptive innate immune response in which Granulocyte-macrophage colony stimulating factor (GM-CSF) plays a key role and which is more commonly elevated in older participants. GSK has therefore determined to urgently confirm these subgroup findings by amending the protocol to allow the enrolment of an additional cohort of participants aged 70 years and above with no upper age limit. GSK has reviewed the results from what is now considered as the first part of the study (Part 1) and decided that a second part will be added to the study (Part 2) which has less frequent assessments to decrease the burden on sites

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab in patients with severe pulmonary COVID-19 related disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Percentage of participants alive and free of respiratory failure at Day 28

Primary: Part 1: Percentage of participants alive and free of respiratory failure at Day 28

Primary: Part 2: Percentage of participants alive and free of respiratory failure at Day 28

Primary: Part 2: Percentage of participants alive and free of respiratory failure at Day 28

Secondary: Part 1: Number of participants who died due to all causes at Day 60

Secondary: Part 1: Number of participants who died due to all causes at Day 60

Secondary: Part 2: Number of participants who died due to all causes at Day 28

Secondary: Part 2: Number of participants who died due to all causes at Day 28

Secondary: Part 2: Number of participants who died due to all causes at Day 60

Secondary: Part 2: Number of participants who died due to all causes at Day 60

Secondary: Part 1: Time to death due to all causes up to Day 60

Secondary: Part 1: Time to death due to all causes up to Day 60

Secondary: Part 2: Time to death due to all causes up to Day 60

Secondary: Part 2: Time to death due to all causes up to Day 60

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 7

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 7

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 14

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 14

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 60

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 60

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 42

Secondary: Part 1: Percentage of participants alive and free of respiratory failure at Day 42

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 7

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 7

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 14

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 14

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 42

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 42

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 60

Secondary: Part 2: Percentage of participants alive and free of respiratory failure at Day 60

Secondary: Part 1: Time to recovery from respiratory failure up to Day 28

Secondary: Part 1: Time to recovery from respiratory failure up to Day 28

Secondary: Part 2: Time to recovery from respiratory failure up to Day 28

Secondary: Part 2: Time to recovery from respiratory failure up to Day 28

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 7

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 7

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 14

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 14

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 28

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 28

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 42

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 42

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 60

Secondary: Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 60

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 7

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 7

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 14

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 14

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 28

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 28

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 42

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 42

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 60

Secondary: Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 60

Secondary: Part 1: Time to last dependence on supplementary oxygen

Secondary: Part 1: Time to last dependence on supplementary oxygen

Secondary: Part 2: Time to last dependence on supplementary oxygen

Secondary: Part 2: Time to last dependence on supplementary oxygen

Secondary: Part 1: Percentage of participants admitted to Intensive Care Unit (ICU) up to Day 28

Secondary: Part 1: Percentage of participants admitted to Intensive Care Unit (ICU) up to Day 28

Secondary: Part 1: Time to final ICU discharge

Secondary: Part 1: Time to final ICU discharge

Secondary: Part 2: Time to final ICU discharge

Secondary: Part 2: Time to final ICU discharge

Secondary: Part 1: Time to first discharge from investigator site up to Day 60

Secondary: Part 1: Time to first discharge from investigator site up to Day 60

Secondary: Part 1: Time to first discharge to non-hospitalized residence up to Day 60

Secondary: Part 1: Time to first discharge to non-hospitalized residence up to Day 60

Secondary: Part 2: Time to first discharge from investigator site up to Day 60

Secondary: Part 2: Time to first discharge from investigator site up to Day 60

Clinical Trial Results:
A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab in patients with severe pulmonary COVID-19 related disease