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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT04376684

Collaborator

(none)

1,156

Enrollment

120

Locations

Arms

14.6

Actual Duration (Months)

9.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

OSCAR (Otilimab in Severe COVID-19 Related Disease) is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. The study is being conducted in 2 parts (Part 1 and Part 2). Otilimab is a human monoclonal anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease in Part 1. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of hospitalized participants with severe COVID-19 related pulmonary disease with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

Condition or Disease	Intervention/Treatment	Phase
Severe Acute Respiratory Syndrome	Biological: Otilimab Biological: Placebo 1 Biological: Placebo 2 Drug: Standard of care	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

1156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.Participants will be randomized to receive either a blinded IV infusion of otilimab or placebo, in addition to standard of care.

Masking:

Double (Participant, Investigator)

Masking Description:

This is a double-blind study.

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease

Actual Study Start Date :

May 28, 2020

Actual Primary Completion Date :

Jul 15, 2021

Actual Study Completion Date :

Aug 16, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Participants receiving otilimab Participants (age >=18 years and <=79 years) will receive a single dose of otilimab administered as an IV infusion in addition to standard of care in Part 1.	Biological: Otilimab Otilimab will be administered once via IV route. Drug: Standard of care All participants will receive standard of care as per institutional protocol.
Placebo Comparator: Part 1: Participants receiving placebo 1 Participants (age >=18 years and <=79 years) will receive a single dose of matching placebo administered as an IV infusion in addition to standard of care in Part 1.	Biological: Placebo 1 Placebo 1 will consist of sterile 0.9 percent (%) sodium chloride solution administered once via IV route. Drug: Standard of care All participants will receive standard of care as per institutional protocol.
Experimental: Part 2: Participants receiving otilimab Participants (age 70 years or above) will receive a single dose of otilimab administered as an IV infusion in addition to standard of care in Part 2.	Biological: Otilimab Otilimab will be administered once via IV route. Drug: Standard of care All participants will receive standard of care as per institutional protocol.
Placebo Comparator: Part 2: Participants receiving placebo 2 Participants (age 70 years or above) will receive a single dose of matching placebo administered as an IV infusion in addition to standard of care in Part 2.	Biological: Placebo 2 Placebo 2 will consist of sterile 5% dextrose or 5% glucose solution administered once via IV route. Drug: Standard of care All participants will receive standard of care as per institutional protocol.

Outcome Measures

Primary Outcome Measures

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28 [At Day 28]
Participants were considered alive and free of respiratory failure if they were in category 1, 2, 3, or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (greater than or equal to [>=]15 liters per minute [L/min]), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28 [At Day 28]
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.

Secondary Outcome Measures

Part 1: Number of Participants Who Died Due to All Causes at Day 60 [At Day 60]
Number of participants who died due to all causes at Day 60 are reported.
Part 2: Number of Participants Who Died Due to All Causes at Day 28 [At Day 28]
Number of participants who died due to all causes at Day 28 is reported
Part 2: Number of Participants Who Died Due to All Causes at Day 60 [At Day 60]
Number of participants who died due to all causes at Day 60 is reported
Part 1: Time to Death Due to All Causes up to Day 60 [Up to Day 60]
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.
Part 2: Time to Death Due to All Causes up to Day 60 [Up to Day 60]
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.
Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7 [At Day 7]
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.
Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14 [At Day 14]
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.
Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42 [At Day 42]
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.
Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60 [At Day 60]
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.
Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7 [At Day 7]
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.
Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14 [At Day 14]
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.
Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42 [At Day 42]
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.
Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60 [At Day 60]
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.
Part 1: Time to Recovery From Respiratory Failure up to Day 28 [Up to Day 28]
Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Part 2: Time to Recovery From Respiratory Failure up to Day 28 [Up to Day 28]
Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7 [At Day 7]
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.
Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14 [At Day 14]
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.
Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28 [At Day 28]
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.
Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42 [At Day 42]
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.
Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60 [At Day 60]
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.
Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7 [At Day 7]
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.
Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14 [At Day 14]
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.
Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28 [At Day 28]
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.
Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42 [At Day 42]
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.
Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60 [At Day 60]
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.
Part 1: Time to Last Dependence on Supplementary Oxygen [Up to Day 28]
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.
Part 2: Time to Last Dependence on Supplementary Oxygen [Up to Day 28]
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.
Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28 [Up to Day 28]
Participants who were admitted to the ICU up to (and including) Day 28 were evaluated. Percentage values are rounded off.
Part 1: Time to Final ICU Discharge [Up to Day 28]
Time to final ICU discharge was defined as the time from dosing to when the participant is discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented.
Part 2: Time to Final ICU Discharge [Up to Day 28]
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.
Part 1: Time to First Discharge From Investigator Site up to Day 60 [Up to Day 60]
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.
Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60 [Up to Day 60]
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.
Part 2: Time to First Discharge From Investigator Site up to Day 60 [Up to Day 60]
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.
Part 2: Time to First Discharge to Non-hospitalized Residence [Up to Day 60]
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.
Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs) [Up to Day 60]
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.
Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs [Up to Day 60]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria for Part 1:

Participants aged >=18 years and <=79 years at the time of obtaining informed consent.
Participants must:

have positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) result (any validated test, for example. reverse transcription polymerase chain reaction [RT-PCR] [performed on an appropriate specimen; for example: respiratory tract sample])
and be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan consistent with COVID-19)
and be developing new onset of oxygenation impairment requiring any of the following:
high-flow oxygen (>=15L/min)
non-invasive ventilation (for example. CPAP, BIPAP)
mechanical ventilation <=48 hours prior to dose
and have increased biological markers of systemic inflammation (either C-reactive protein [CRP] >upper limit of normal [ULN] or serum ferritin >ULN).

No gender restriction.
Female participants must meet and agree to abide by the contraceptive criteria detailed in the protocol. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding or if she is using highly effective contraceptive methods. Women of non-childbearing potential can also participate. A negative highly sensitive pregnancy test at hospital admission or before the first dose of study intervention.
Capable of giving written informed consent.

Inclusion Criteria for Part 2:

Participants aged 70 years or above at the time of obtaining informed consent.
Participants must:

have positive SARS-CoV-2 result (any validated test, for example. RT-PCR [performed on an appropriate specimen; for example. respiratory tract sample])
and be hospitalized due to diagnosis of pneumonia (chest X-ray or CT scan consistent with COVID-19).
and be developing new onset of oxygenation impairment requiring any of the following:
high-flow oxygen (>=15L/min)
non-invasive ventilation (for example. CPAP, BiPAP)
mechanical ventilation <=48 hours prior to dose
and have increased biological markers of systemic inflammation (either CRP >ULN or serum ferritin >ULN.

No gender restriction.
Capable of giving written informed consent.

Exclusion Criteria for Part 1:

Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
Multiple organ failure according to the investigator's judgement or a Sequential Organ Failure assessment (SOFA score) >10 if in the ICU.
Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis or high-dose (>0.15 micrograms [mcg]/kilograms [kg]/min) noradrenaline (or equivalent) or more than one vasopressor.
Current serious or uncontrolled medical condition (for example: significant pulmonary disease [such as severe chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis], heart failure [New York Heart Association class III or higher], renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months) or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-CoV-2).
Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
Known Human Immunodeficiency Virus (HIV) regardless of immunological status.
Known hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (HCV) positive.
Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy.
Received monoclonal antibody therapy (for examplee. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin, or planned to be received, during the study.
Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, Janus Kinase (JAK) inhibitors (for examplee. baricitinib, tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned to be received during the study.
History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy.
Received COVID-19 convalescent plasma within 48 hours of randomization.
Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 milligrams (mg) or equivalent per day.
Treatment with an investigational drug within 30 days of randomization.
Participating in other drug clinical trials, including for COVID-19.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times ULN.
Platelets <50,000/cubic millimeters (mm^3)
Hemoglobin <=9 grams per deciliter (g/dL)
Absolute neutrophil count (ANC) <1.5 times 10^9/L (neutropenia >= Grade 2)
Estimated glomerular filtration rate (GFR) <=30 milliliters (mL)/min/1.73 meter square (/m^2).
Pregnant or breastfeeding females.

Exclusion Criteria for Part 2:

Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
Multiple organ failure according to the investigator's judgement or a SOFA score >10 if intubated in the ICU.
ECMO hemofiltration/dialysis, or more than one inotrope/vasopressor of any class.
Current serious or uncontrolled medical condition (for example. significant pulmonary disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class III or higher], severe renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months), severe dementia, severe disability, or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
Untreated systemic bacterial, fungal, viral, or other infection (other than SARSCoV-2).
Known active TB, history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
Known HIV regardless of immunological status.
Known HBsAg and/or anti-HCV positive (participants demonstrating a sustained virologic response (SVR) are not excluded from participation).
Currently receiving radiotherapy, chemotherapy (hormone based therapies are permitted) or immunotherapy for malignancy.
Received monoclonal antibody therapy (for example. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin, or planned to be received during the study.
Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors (for example. baricitinib, tofacitinib, upadacitinib), nintedanib, disease modifying antirheumatic drugs (DMARDs) (for example. methotrexate) within the last 3 months prior to randomization or planned to be received during the study.
History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy.
Received COVID-19 convalescent plasma within 48 hours of randomization.
Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition at a dose higher than prednisone 10 mg or equivalent per day.
Treatment with an investigational drug or substance within 30 days of randomization unless approved by the Medical Monitor.
Participating in other drug clinical trials, including for COVID-19.
AST or ALT >5 times ULN.
Platelets <50,000/mm^3.
Hemoglobin <=9 g/dL
ANC <1.0 x 10^9/L (neutropenia >= Grade 3).
Estimated GFR <=30 mL/min/1.73 m^2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Mobile	Alabama	United States	36608
2	GSK Investigational Site	Little Rock	Arkansas	United States	72205
3	GSK Investigational Site	Sacramento	California	United States	95819
4	GSK Investigational Site	Torrance	California	United States	90502
5	GSK Investigational Site	Gainesville	Florida	United States	32608
6	GSK Investigational Site	Winfield	Illinois	United States	60190
7	GSK Investigational Site	Baltimore	Maryland	United States	21201
8	GSK Investigational Site	Germantown	Maryland	United States	20876
9	GSK Investigational Site	Silver Spring	Maryland	United States	20910
10	GSK Investigational Site	Saint Louis Park	Minnesota	United States	55426
11	GSK Investigational Site	Saint Paul	Minnesota	United States	55101
12	GSK Investigational Site	Jackson	Mississippi	United States	39216
13	GSK Investigational Site	Reno	Nevada	United States	89502
14	GSK Investigational Site	Buffalo	New York	United States	14215-1199
15	GSK Investigational Site	Charlotte	North Carolina	United States	28203
16	GSK Investigational Site	Toledo	Ohio	United States	43608
17	GSK Investigational Site	Doylestown	Pennsylvania	United States	18901
18	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
19	GSK Investigational Site	Roanoke	Virginia	United States	24017
20	GSK Investigational Site	Tacoma	Washington	United States	98405
21	GSK Investigational Site	Milwaukee	Wisconsin	United States	53295
22	GSK Investigational Site	Munro	Buenos Aires	Argentina	1605
23	GSK Investigational Site	Cordoba	Córdova	Argentina	X5000
24	GSK Investigational Site	Buenos Aires		Argentina	1842
25	GSK Investigational Site	Buenos Aires		Argentina	C1039AAO
26	GSK Investigational Site	Cordoba		Argentina	5000
27	GSK Investigational Site	Cordoba		Argentina	X5002AOQ
28	GSK Investigational Site	Brussel		Belgium	1090
29	GSK Investigational Site	Yvoir		Belgium	5530
30	GSK Investigational Site	Belo Horizonte	Minas Gerais	Brazil	30130-100
31	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
32	GSK Investigational Site	São Paulo		Brazil	01246-090
33	GSK Investigational Site	São Paulo		Brazil	01323903
34	GSK Investigational Site	São Paulo		Brazil	04037-003
35	GSK Investigational Site	São Paulo		Brazil	05403-010
36	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 1Y6
37	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
38	GSK Investigational Site	Ottawa	Ontario	Canada	K1Y 4E9
39	GSK Investigational Site	Montréal	Quebec	Canada	H4J 1C5
40	GSK Investigational Site	QC	Quebec	Canada	J5R 6J5
41	GSK Investigational Site	St-Jerome	Quebec	Canada	J7Z 5T3
42	GSK Investigational Site	Santiago		Chile	7630000
43	GSK Investigational Site	Santiago		Chile	8900085
44	GSK Investigational Site	Bogotá		Colombia	111971
45	GSK Investigational Site	Amiens Cedex 1		France	80054
46	GSK Investigational Site	Angers Cedex 9		France	49933
47	GSK Investigational Site	Argenteuil		France	95100
48	GSK Investigational Site	La Roche-Sur-Yon		France	85925
49	GSK Investigational Site	La Tronche		France	38700
50	GSK Investigational Site	Limoges Cedex		France	87042
51	GSK Investigational Site	Melun		France	77000
52	GSK Investigational Site	Paris		France	75013
53	GSK Investigational Site	Pierre-Bénite		France	69495
54	GSK Investigational Site	Strasbourg cedex		France	67098
55	GSK Investigational Site	Strasbourg		France	67000
56	GSK Investigational Site	Valenciennes Cedex		France	59322
57	GSK Investigational Site	Aurangabad		India	431001
58	GSK Investigational Site	Aurangabad		India	431003
59	GSK Investigational Site	Hyderabad		India	500018
60	GSK Investigational Site	Kolkata		India	700094
61	GSK Investigational Site	Kolkata		India	700099
62	GSK Investigational Site	Mumbai		India	400034
63	GSK Investigational Site	Nagpur		India	440003
64	GSK Investigational Site	New Delhi		India	110017
65	GSK Investigational Site	Pune		India	411001
66	GSK Investigational Site	Pune		India	411013
67	GSK Investigational Site	Napoli	Campania	Italy	80100
68	GSK Investigational Site	Aichi		Japan	470-1192
69	GSK Investigational Site	Kanagawa		Japan	231-8682
70	GSK Investigational Site	Kanagawa		Japan	251-0041
71	GSK Investigational Site	Osaka		Japan	534-0021
72	GSK Investigational Site	Saitama		Japan	350-0495
73	GSK Investigational Site	Tokyo		Japan	113-8519
74	GSK Investigational Site	Tokyo		Japan	150-8935
75	GSK Investigational Site	Tokyo		Japan	162-8543
76	GSK Investigational Site	Tokyo		Japan	162-8655
77	GSK Investigational Site	Mexico City	Ciudad De Mexico	Mexico	14080
78	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44280
79	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64710
80	GSK Investigational Site	Mexico		Mexico	14000
81	GSK Investigational Site	Breda		Netherlands	4818 CK
82	GSK Investigational Site	Den Bosch		Netherlands	5223 GZ
83	GSK Investigational Site	Enschede		Netherlands	7512 KZ
84	GSK Investigational Site	Nijmegen		Netherlands	6532 SZ
85	GSK Investigational Site	Rotterdam		Netherlands	3083 AN
86	GSK Investigational Site	Lima		Peru	Callao 2
87	GSK Investigational Site	Lima		Peru	Lima 11
88	GSK Investigational Site	Lima		Peru	Lima 1
89	GSK Investigational Site	Bydgoszcz		Poland	85-030
90	GSK Investigational Site	Krakow		Poland	30-688
91	GSK Investigational Site	Poznan		Poland	61-285
92	GSK Investigational Site	Warszawa		Poland	02-507
93	GSK Investigational Site	Wroclaw		Poland	51-149
94	GSK Investigational Site	Barnaul		Russian Federation	656045
95	GSK Investigational Site	Chelyabinsk		Russian Federation	454034
96	GSK Investigational Site	Ekaterinburg		Russian Federation	620039
97	GSK Investigational Site	Moscow		Russian Federation	111539
98	GSK Investigational Site	Nizhniy Novgorod		Russian Federation	603011
99	GSK Investigational Site	Omsk		Russian Federation	644111
100	GSK Investigational Site	Perm		Russian Federation	614990
101	GSK Investigational Site	St. Petersburg		Russian Federation	191104
102	GSK Investigational Site	Ufa		Russian Federation	450083
103	GSK Investigational Site	Voronezh		Russian Federation	394066
104	GSK Investigational Site	Benoni	Gauteng	South Africa	1501
105	GSK Investigational Site	Johannesburg	Gauteng	South Africa	2193
106	GSK Investigational Site	Durban	KwaZulu- Natal	South Africa	4052
107	GSK Investigational Site	Panorama,		South Africa	7500
108	GSK Investigational Site	Tygerberg		South Africa	7505
109	GSK Investigational Site	Worcester		South Africa	6850
110	GSK Investigational Site	Barcelona		Spain	08003
111	GSK Investigational Site	L'Hospitalet de Llobregat		Spain	08907
112	GSK Investigational Site	Logroño		Spain	26006
113	GSK Investigational Site	Madrid		Spain	28006
114	GSK Investigational Site	Madrid		Spain	28007
115	GSK Investigational Site	Madrid		Spain	28040
116	GSK Investigational Site	Madrid		Spain	28055
117	GSK Investigational Site	San Sebastián De Los Reyes/Madrid		Spain	28702
118	GSK Investigational Site	Manchester	Greater Manchester	United Kingdom	M13 9WL
119	GSK Investigational Site	Liverpool		United Kingdom	L7 8XP
120	GSK Investigational Site	Newcastle Upon Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT04376684

Other Study ID Numbers:

214094

First Posted:

May 6, 2020

Last Update Posted:

Mar 23, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GlaxoSmithKline

Additional relevant MeSH terms:

COVID-19

Severe Acute Respiratory Syndrome

Study Results

Participant Flow

Recruitment Details	This was a 2-part study evaluating efficacy and safety of intravenously (IV) administered otilimab in participants with severe pulmonary Coronavirus Disease-2019 (COVID-19) related disease. Part 1 consisted of participants aged 18 to 79 years and Part 2 consisted of participants aged 70 years and older.
Pre-assignment Detail	A total of 1156 (806 in Part 1 and 350 in Part 2) participants were enrolled in the study (Enrolled Population: All participants who entered the study).

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Period Title: Part 1 (Up to Day 60)
STARTED	403	403	0	0
COMPLETED	388	379	0	0
NOT COMPLETED	15	24	0	0
Period Title: Part 1 (Up to Day 60)
STARTED	0	0	175	175
COMPLETED	0	0	170	171
NOT COMPLETED	0	0	5	4

Baseline Characteristics

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg	Total
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.	Total of all reporting groups
Overall Participants	403	403	175	175	1156
Age, Customized (Count of Participants)
<18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 to 64 years	249 61.8%	250 62%	0 0%	0 0%	499 43.2%
>=65 to 84 years	154 38.2%	153 38%	168 96%	168 96%	643 55.6%
>=85 years	0 0%	0 0%	7 4%	7 4%	14 1.2%
Sex: Female, Male (Count of Participants)
Female	128 31.8%	101 25.1%	75 42.9%	73 41.7%	377 32.6%
Male	275 68.2%	302 74.9%	100 57.1%	102 58.3%	779 67.4%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	24 6%	30 7.4%	3 1.7%	8 4.6%	65 5.6%
Asian - Central/South Asian Heritage	42 10.4%	31 7.7%	1 0.6%	0 0%	74 6.4%
Asian - East Asian Heritage	4 1%	4 1%	0 0%	0 0%	8 0.7%
Asian - Japanese Heritage	15 3.7%	14 3.5%	13 7.4%	5 2.9%	47 4.1%
Asian - South East Asian Heritage	12 3%	8 2%	1 0.6%	0 0%	21 1.8%
Black or African American	25 6.2%	26 6.5%	6 3.4%	6 3.4%	63 5.4%
White - Arabic/North African Heritage	27 6.7%	21 5.2%	14 8%	21 12%	83 7.2%
White - White/Caucasian/European Heritage	235 58.3%	251 62.3%	136 77.7%	134 76.6%	756 65.4%
Mixed Asian Race	0 0%	1 0.2%	0 0%	0 0%	1 0.1%
Mixed White Race	1 0.2%	1 0.2%	1 0.6%	0 0%	3 0.3%
Multiple	7 1.7%	7 1.7%	0 0%	0 0%	14 1.2%
Unknown	11 2.7%	9 2.2%	0 0%	1 0.6%	21 1.8%

Outcome Measures

1. Primary Outcome

Title	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Description	Participants were considered alive and free of respiratory failure if they were in category 1, 2, 3, or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (greater than or equal to [>=]15 liters per minute [L/min]), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 28

Outcome Measure Data

Analysis Population Description
Modified intent to treat (mITT) Population consisted of all randomized participants who received study intervention. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	393	389
Number [Percentage of participants]	67 16.6%	71 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0456
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95% 0.96 to 1.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

2. Primary Outcome

Title	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	172
Number [Percentage of participants]	51 12.7%	52 12.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8574
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.67 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

3. Secondary Outcome

Title	Part 1: Number of Participants Who Died Due to All Causes at Day 60
Description	Number of participants who died due to all causes at Day 60 are reported.
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	386	373
Count of Participants [Participants]	93 23.1%	84 20.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2057
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.61 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

4. Secondary Outcome

Title	Part 2: Number of Participants Who Died Due to All Causes at Day 28
Description	Number of participants who died due to all causes at Day 28 is reported
Time Frame	At Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	172
Count of Participants [Participants]	70 17.4%	63 15.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3061
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95% 0.50 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

5. Secondary Outcome

Title	Part 2: Number of Participants Who Died Due to All Causes at Day 60
Description	Number of participants who died due to all causes at Day 60 is reported
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	171
Count of Participants [Participants]	76 18.9%	74 18.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6665
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.59 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

6. Secondary Outcome

Title	Part 1: Time to Death Due to All Causes up to Day 60
Description	Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	93	84
Median (Inter-Quartile Range) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1942
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95% 0.65 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

7. Secondary Outcome

Title	Part 2: Time to Death Due to All Causes up to Day 60
Description	Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	76	74
Median (Inter-Quartile Range) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5324
	Comments	p-value is generated from a two-sided test
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.65 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

8. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 7

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	396	393
Number [Percentage of participants]	42 10.4%	44 10.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2871
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95% 0.80 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

9. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 14

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	394	391
Number [Percentage of participants]	61 15.1%	63 15.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1754
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95% 0.85 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

10. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 42

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	392	385
Number [Percentage of participants]	70 17.4%	74 18.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0616
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95% 0.93 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

11. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	386	373
Number [Percentage of participants]	74 18.4%	75 18.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1830
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% 0.84 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

12. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 7

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	173	174
Number [Percentage of participants]	28 6.9%	37 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0831
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95% 0.95 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

13. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 14

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	171	174
Number [Percentage of participants]	43 10.7%	49 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2557
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95% 0.83 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

14. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 42

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	172
Number [Percentage of participants]	54 13.4%	54 13.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8560
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.67 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

15. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60
Description	Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off.
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	171
Number [Percentage of participants]	55 13.6%	56 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7533
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95% 0.69 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

16. Secondary Outcome

Title	Part 1: Time to Recovery From Respiratory Failure up to Day 28
Description	Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	263	281
Median (Inter-Quartile Range) [Days]	10	9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0959
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.95 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

17. Secondary Outcome

Title	Part 2: Time to Recovery From Respiratory Failure up to Day 28
Description	Time to recovery from respiratory failure was defined as the time (days) from dosing to last recovery from respiratory failure up to (and including) Day 28. Participants were in respiratory failure if they were in category 5 or above from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Median and inter-quartile range (first quartile and third quartile) of time to recovery from respiratory failure are presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	90	91
Median (Inter-Quartile Range) [Days]	24	22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4421
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.84 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

18. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 7

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	396	393
Number [Percentage of participants]	11 2.7%	12 3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2814
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95% 0.73 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

19. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 14

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	394	391
Number [Percentage of participants]	37 9.2%	37 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3901
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.77 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

20. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	393	389
Number [Percentage of participants]	57 14.1%	57 14.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4763
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.75 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

21. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 42

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	392	385
Number [Percentage of participants]	63 15.6%	66 16.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1973
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95% 0.84 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

22. Secondary Outcome

Title	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	386	373
Number [Percentage of participants]	67 16.6%	71 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1173
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95% 0.88 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.

23. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 7

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	173	174
Number [Percentage of participants]	3 0.7%	13 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0037
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.98
	Confidence Interval	(2-Sided) 95% 1.57 to 10.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

24. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 14

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	171	174
Number [Percentage of participants]	23 5.7%	28 6.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3581
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95% 0.77 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

25. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	172
Number [Percentage of participants]	39 9.7%	38 9.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9621
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% 0.63 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

26. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 42

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	172
Number [Percentage of participants]	46 11.4%	41 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4167
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.54 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

27. Secondary Outcome

Title	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60
Description	Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off.
Time Frame	At Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	170	171
Number [Percentage of participants]	51 12.7%	46 11.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3408
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95% 0.53 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

28. Secondary Outcome

Title	Part 1: Time to Last Dependence on Supplementary Oxygen
Description	Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	223	221
Median (Inter-Quartile Range) [Days]	22	21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4250
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.85 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

29. Secondary Outcome

Title	Part 2: Time to Last Dependence on Supplementary Oxygen
Description	Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	66	68
Median (Inter-Quartile Range) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4774
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95% 0.81 to 1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

30. Secondary Outcome

Title	Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28
Description	Participants who were admitted to the ICU up to (and including) Day 28 were evaluated. Percentage values are rounded off.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population (not in ICU at Baseline) comprised of participants in the mITT population who were not in the ICU at Baseline. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	98	95
Number [Percentage of participants]	29 7.2%	16 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0119
	Comments	p-value is from a one-sided test.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95% 0.18 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.

31. Secondary Outcome

Title	Part 1: Time to Final ICU Discharge
Description	Time to final ICU discharge was defined as the time from dosing to when the participant is discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population admitted to ICU at Baseline comprised of those participants in mITT who were admitted to ICU at Baseline. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	300	300
Median (Inter-Quartile Range) [Days]	13	15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4404
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.83 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

32. Secondary Outcome

Title	Part 2: Time to Final ICU Discharge
Description	Time to final ICU discharge was defined as the time from dosing to when the participant was discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
mITT Population admitted to ICU at Baseline. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	38	44
Median (Inter-Quartile Range) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6253
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.72 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

33. Secondary Outcome

Title	Part 1: Time to First Discharge From Investigator Site up to Day 60
Description	Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site (IS) up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	288	294
Median (Inter-Quartile Range) [Days]	18	18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1078
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.94 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

34. Secondary Outcome

Title	Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60
Description	Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge to non-hospitalized residence is presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	269	280
Median (Inter-Quartile Range) [Days]	21	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1140
	Comments	p-value is from a one-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95% 0.94 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.

35. Secondary Outcome

Title	Part 2: Time to First Discharge From Investigator Site up to Day 60
Description	Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	96	99
Median (Inter-Quartile Range) [Days]	36	37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7084
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95% 0.80 to 1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

36. Secondary Outcome

Title	Part 2: Time to First Discharge to Non-hospitalized Residence
Description	Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge to non-hospitalized residence is presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
mITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	86	90
Median (Inter-Quartile Range) [Days]	NA	53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Placebo 1, Part 1: Otilimab 90 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4085
	Comments	p-value is generated from a two-sided test.
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95% 0.84 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.

37. Secondary Outcome

Title	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
Safety population comprised of all participants who received study intervention

Arm/Group Title	Part 1: Placebo 1	Part 1: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.	Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	396	397
Non-SAEs	67 16.6%	91 22.6%
SAEs	147 36.5%	124 30.8%

38. Secondary Outcome

Title	Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented.
Time Frame	Up to Day 60

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Part 2: Placebo 2	Part 2: Otilimab 90 mg
Arm/Group Description	Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.	Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
Measure Participants	173	174
Non-SAEs	57 14.1%	50 12.4%
SAEs	90 22.3%	90 22.3%

Adverse Events

	Part 1: Placebo 1		Part 1: Otilimab 90 mg		Part 2: Placebo 2		Part 2: Otilimab 90 mg
Time Frame	All-cause mortality, SAEs, and non-SAEs were collected up to Day 60 in Part 1 and 2 of the study
Adverse Event Reporting Description	SAEs and non-serious AEs were reported for the Safety Population which comprised of all participants who received study intervention. All-cause mortality was reported for Enrolled population (all participants who entered the study). Sixteen participants from Enrolled Population (N=1156) did not receive study treatment, hence were not included in Safety Population (N=1140).

Arm/Group Title	Part 1: Placebo 1		Part 1: Otilimab 90 mg		Part 2: Placebo 2		Part 2: Otilimab 90 mg
Arm/Group Description	Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care.		Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care.		Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care.		Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/403 (23.1%)		84/403 (20.8%)		76/175 (43.4%)		74/175 (42.3%)
Serious Adverse Events
	Part 1: Placebo 1		Part 1: Otilimab 90 mg		Part 2: Placebo 2		Part 2: Otilimab 90 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/396 (37.1%)		124/397 (31.2%)		90/173 (52%)		90/174 (51.7%)
Blood and lymphatic system disorders
Coagulopathy	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Cardiac disorders
Cardiac arrest	4/396 (1%)	4	8/397 (2%)	11	7/173 (4%)	9	4/174 (2.3%)	4
Cardio-respiratory arrest	1/396 (0.3%)	1	2/397 (0.5%)	2	4/173 (2.3%)	4	7/174 (4%)	7
Atrial fibrillation	3/396 (0.8%)	3	1/397 (0.3%)	1	2/173 (1.2%)	2	2/174 (1.1%)	2
Myocardial infarction	0/396 (0%)	0	2/397 (0.5%)	2	1/173 (0.6%)	1	2/174 (1.1%)	2
Supraventricular tachycardia	1/396 (0.3%)	2	0/397 (0%)	0	1/173 (0.6%)	1	1/174 (0.6%)	1
Bradycardia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Cardiac failure	0/396 (0%)	0	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Cardiogenic shock	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Cardiopulmonary failure	1/396 (0.3%)	1	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Sinus node dysfunction	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Acute myocardial infarction	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Atrial flutter	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Cardiac failure congestive	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Cardiovascular insufficiency	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Left ventricular failure	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Myocarditis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Paroxysmal atrioventricular block	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pneumopericardium	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pulseless electrical activity	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Right ventricular failure	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Intestinal ischaemia	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Upper gastrointestinal haemorrhage	1/396 (0.3%)	1	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Gastric ulcer	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Gastric ulcer haemorrhage	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Gastric varices haemorrhage	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Intestinal perforation	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Rectal ulcer haemorrhage	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Retroperitoneal haematoma	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Retroperitoneal haemorrhage	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Small intestinal obstruction	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
General disorders
Multiple organ dysfunction syndrome	15/396 (3.8%)	15	12/397 (3%)	12	8/173 (4.6%)	8	6/174 (3.4%)	6
Catheter site haemorrhage	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Chest pain	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Complication associated with device	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hyperthermia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Pyrexia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Systemic inflammatory response syndrome	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Hepatobiliary disorders
Ischaemic hepatitis	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Acute hepatic failure	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Cholecystitis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Cholestasis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Haemorrhagic cholecystitis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hepatitis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Hepatitis fulminant	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hepatocellular injury	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Immune system disorders
Haemophagocytic lymphohistiocytosis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Infections and infestations
Septic shock	13/396 (3.3%)	14	14/397 (3.5%)	14	5/173 (2.9%)	5	8/174 (4.6%)	8
Pneumonia	9/396 (2.3%)	9	7/397 (1.8%)	7	5/173 (2.9%)	5	6/174 (3.4%)	6
COVID-19 pneumonia	3/396 (0.8%)	3	12/397 (3%)	12	4/173 (2.3%)	4	5/174 (2.9%)	5
COVID-19	5/396 (1.3%)	5	3/397 (0.8%)	3	9/173 (5.2%)	9	6/174 (3.4%)	6
Sepsis	7/396 (1.8%)	7	1/397 (0.3%)	1	2/173 (1.2%)	2	4/174 (2.3%)	4
Pneumonia staphylococcal	6/396 (1.5%)	6	1/397 (0.3%)	1	1/173 (0.6%)	1	4/174 (2.3%)	4
Pneumonia pseudomonal	7/396 (1.8%)	7	2/397 (0.5%)	2	0/173 (0%)	0	0/174 (0%)	0
Klebsiella sepsis	4/396 (1%)	4	1/397 (0.3%)	1	1/173 (0.6%)	1	2/174 (1.1%)	2
Staphylococcal bacteraemia	1/396 (0.3%)	1	1/397 (0.3%)	1	1/173 (0.6%)	1	4/174 (2.3%)	4
Staphylococcal sepsis	2/396 (0.5%)	3	3/397 (0.8%)	3	0/173 (0%)	0	1/174 (0.6%)	1
Staphylococcal infection	0/396 (0%)	0	4/397 (1%)	4	0/173 (0%)	0	1/174 (0.6%)	1
Bronchopulmonary aspergillosis	3/396 (0.8%)	3	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Enterobacter pneumonia	2/396 (0.5%)	3	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Pneumonia klebsiella	2/396 (0.5%)	2	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Bacterial sepsis	2/396 (0.5%)	2	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Pneumonia bacterial	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Pneumonia haemophilus	3/396 (0.8%)	5	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pneumonia serratia	3/396 (0.8%)	3	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Urosepsis	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Acinetobacter infection	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Bacteraemia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Device related bacteraemia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Enterococcal infection	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Escherichia sepsis	0/396 (0%)	0	2/397 (0.5%)	2	0/173 (0%)	0	0/174 (0%)	0
Lung abscess	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Pneumonia acinetobacter	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Pneumonia proteus	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Pneumonia streptococcal	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Pseudomonal bacteraemia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Pulmonary sepsis	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	2/174 (1.1%)	2
Stenotrophomonas infection	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Tracheobronchitis bacterial	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Urinary tract infection	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Acinetobacter sepsis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Bacterial infection	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Candida pneumonia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Citrobacter infection	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Citrobacter sepsis	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Clostridium difficile colitis	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Coronavirus infection	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Device related sepsis	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Diverticulitis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Enterobacter sepsis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Fusobacterium infection	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Lactobacillus infection	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Mycetoma mycotic	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Oral candidiasis	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Peritonitis	1/396 (0.3%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pneumonia escherichia	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Pneumonia pneumococcal	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pseudomembranous colitis	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Serratia bacteraemia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Soft tissue infection	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Superinfection	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Tracheitis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Tracheobronchitis	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Urinary tract infection enterococcal	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Injury, poisoning and procedural complications
Multiple injuries	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Subdural haematoma	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Tracheal injury	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Investigations
Oxygen consumption increased	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Oxygen saturation decreased	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Haemoglobin decreased	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Liver function test abnormal	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Liver function test increased	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Pulmonary function test decreased	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Transaminases increased	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Troponin T increased	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Metabolism and nutrition disorders
Failure to thrive	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	2/174 (1.1%)	2
Metabolic acidosis	3/396 (0.8%)	3	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hypernatraemia	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Acidosis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Gout	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hypokalaemia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Lactic acidosis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Musculoskeletal and connective tissue disorders
Haematoma muscle	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Oesophageal adenocarcinoma	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Nervous system disorders
Ischaemic stroke	0/396 (0%)	0	1/397 (0.3%)	1	3/173 (1.7%)	3	0/174 (0%)	0
Cerebral haemorrhage	1/396 (0.3%)	1	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Intensive care unit acquired weakness	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	3/174 (1.7%)	3
Cerebrovascular accident	0/396 (0%)	0	0/397 (0%)	0	2/173 (1.2%)	2	0/174 (0%)	0
Encephalopathy	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Subarachnoid haemorrhage	0/396 (0%)	0	2/397 (0.5%)	2	0/173 (0%)	0	0/174 (0%)	0
Haemorrhage intracranial	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Haemorrhagic stroke	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Hypercapnic coma	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Hypoxic-ischaemic encephalopathy	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Psychiatric disorders
Organic brain syndrome	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Renal and urinary disorders
Acute kidney injury	10/396 (2.5%)	11	9/397 (2.3%)	9	1/173 (0.6%)	1	6/174 (3.4%)	6
Oliguria	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Prerenal failure	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Renal failure	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	18/396 (4.5%)	18	17/397 (4.3%)	18	8/173 (4.6%)	8	6/174 (3.4%)	6
Acute respiratory failure	10/396 (2.5%)	10	9/397 (2.3%)	9	9/173 (5.2%)	9	6/174 (3.4%)	6
Acute respiratory distress syndrome	9/396 (2.3%)	9	11/397 (2.8%)	11	3/173 (1.7%)	3	3/174 (1.7%)	3
Hypoxia	5/396 (1.3%)	5	5/397 (1.3%)	5	7/173 (4%)	7	4/174 (2.3%)	4
Pneumothorax	9/396 (2.3%)	10	8/397 (2%)	8	1/173 (0.6%)	1	3/174 (1.7%)	3
Pulmonary embolism	11/396 (2.8%)	11	6/397 (1.5%)	6	3/173 (1.7%)	3	1/174 (0.6%)	1
Respiratory distress	2/396 (0.5%)	2	2/397 (0.5%)	2	5/173 (2.9%)	5	5/174 (2.9%)	5
Respiratory disorder	1/396 (0.3%)	1	0/397 (0%)	0	3/173 (1.7%)	3	3/174 (1.7%)	3
Pneumomediastinum	3/396 (0.8%)	3	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Organising pneumonia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	2/174 (1.1%)	2
Pulmonary fibrosis	1/396 (0.3%)	1	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Dyspnoea	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Interstitial lung disease	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Laryngeal oedema	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pleural effusion	2/396 (0.5%)	2	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pneumothorax spontaneous	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	1/174 (0.6%)	1
Acute pulmonary oedema	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Bronchospasm	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Haemothorax	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hypercapnia	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Pneumonia aspiration	0/396 (0%)	0	0/397 (0%)	0	0/173 (0%)	0	1/174 (0.6%)	1
Pulmonary oedema	0/396 (0%)	0	0/397 (0%)	0	1/173 (0.6%)	1	0/174 (0%)	0
Respiratory arrest	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Stridor	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Tachypnoea	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Vocal cord dysfunction	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Subcutaneous emphysema	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Toxic epidermal necrolysis	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Social circumstances
Homeless	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Vascular disorders
Shock	4/396 (1%)	4	0/397 (0%)	0	3/173 (1.7%)	3	2/174 (1.1%)	2
Hypotension	3/396 (0.8%)	3	1/397 (0.3%)	1	2/173 (1.2%)	2	1/174 (0.6%)	1
Deep vein thrombosis	2/396 (0.5%)	2	0/397 (0%)	0	2/173 (1.2%)	2	1/174 (0.6%)	1
Shock haemorrhagic	5/396 (1.3%)	5	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Circulatory collapse	0/396 (0%)	0	1/397 (0.3%)	1	1/173 (0.6%)	1	0/174 (0%)	0
Embolism	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Peripheral artery thrombosis	1/396 (0.3%)	1	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Peripheral ischaemia	2/396 (0.5%)	3	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Arterial haemorrhage	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Extremity necrosis	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Haematoma	1/396 (0.3%)	1	0/397 (0%)	0	0/173 (0%)	0	0/174 (0%)	0
Hypovolaemic shock	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Orthostatic hypotension	0/396 (0%)	0	1/397 (0.3%)	1	0/173 (0%)	0	0/174 (0%)	0
Other (Not Including Serious) Adverse Events
	Part 1: Placebo 1		Part 1: Otilimab 90 mg		Part 2: Placebo 2		Part 2: Otilimab 90 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/396 (24.5%)		115/397 (29%)		57/173 (32.9%)		51/174 (29.3%)
Blood and lymphatic system disorders
Anaemia	22/396 (5.6%)	22	18/397 (4.5%)	19	10/173 (5.8%)	10	11/174 (6.3%)	11
Cardiac disorders
Atrial fibrillation	15/396 (3.8%)	15	11/397 (2.8%)	13	10/173 (5.8%)	11	7/174 (4%)	7
Gastrointestinal disorders
Constipation	35/396 (8.8%)	35	39/397 (9.8%)	42	15/173 (8.7%)	16	16/174 (9.2%)	16
Infections and infestations
Pneumonia	21/396 (5.3%)	21	37/397 (9.3%)	43	12/173 (6.9%)	12	6/174 (3.4%)	7
Urinary tract infection	13/396 (3.3%)	13	12/397 (3%)	13	10/173 (5.8%)	10	5/174 (2.9%)	5
Metabolism and nutrition disorders
Hyperglycaemia	14/396 (3.5%)	15	12/397 (3%)	13	4/173 (2.3%)	5	10/174 (5.7%)	14
Hypernatraemia	9/396 (2.3%)	9	20/397 (5%)	22	1/173 (0.6%)	1	3/174 (1.7%)	4
Fluid overload	2/396 (0.5%)	2	1/397 (0.3%)	1	5/173 (2.9%)	5	9/174 (5.2%)	10
Renal and urinary disorders
Acute kidney injury	17/396 (4.3%)	18	15/397 (3.8%)	16	11/173 (6.4%)	13	8/174 (4.6%)	9
Vascular disorders
Hypotension	13/396 (3.3%)	17	13/397 (3.3%)	14	11/173 (6.4%)	13	9/174 (5.2%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT04376684

Other Study ID Numbers:

214094

First Posted:

May 6, 2020

Last Update Posted:

Mar 23, 2022

Last Verified:

Mar 1, 2022