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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04376684

Acronym

OSCAR

Enrollment

1156

Registered

2020-05-06

Start date

2020-05-28

Completion date

2021-08-16

Last updated

2024-09-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Severe Acute Respiratory Syndrome

Keywords

COVID-19, Otilimab, Ordinal scale, Coronavirus, GSK3196165

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.

Interventions

BIOLOGICALOtilimab

Otilimab will be administered once via IV route.

BIOLOGICALPlacebo 1

Placebo 1 will consist of sterile 0.9 percent (%) sodium chloride solution administered once via IV route.

BIOLOGICALPlacebo 2

Placebo 2 will consist of sterile 5% dextrose or 5% glucose solution administered once via IV route.

DRUGStandard of care

All participants will receive standard of care as per institutional protocol.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

This is a double-blind study.

Intervention model description

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

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

for Part 1: * Participants aged \>=18 years and \<=79 years at the time of obtaining informed consent. * Participants must: 1. have positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) result (any validated test, for example. reverse transcription polymerase chain reaction \[RT-PCR\] \[performed on an appropriate specimen; for example: respiratory tract sample\]) 2. and be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography \[CT\] scan consistent with COVID-19) 3. and be developing new onset of oxygenation impairment requiring any of the following: 1. high-flow oxygen (\>=15L/min) 2. non-invasive ventilation (for example. CPAP, BIPAP) 3. mechanical ventilation \<=48 hours prior to dose 4. 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: 1. have positive SARS-CoV-2 result (any validated test, for example. RT-PCR \[performed on an appropriate specimen; for example. respiratory tract sample\]) 2. and be hospitalized due to diagnosis of pneumonia (chest X-ray or CT scan consistent with COVID-19). 3. and be developing new onset of oxygenation impairment requiring any of the following: 1. high-flow oxygen (\>=15L/min) 2. non-invasive ventilation (for example. CPAP, BiPAP) 3. mechanical ventilation \<=48 hours prior to dose 4. 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 \[New York Heart Association {NYHA} class III or higher\], 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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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: 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 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: 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 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 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.
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 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

Countries

Argentina, Belgium, Brazil, Canada, Chile, Colombia, France, India, Italy, Japan, Mexico, Netherlands, Peru, Poland, Russia, South Africa, Spain, United Kingdom, United States

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 details

A total of 1156 (806 in Part 1 and 350 in Part 2) participants were enrolled in the study (Enrolled Population: All participants who entered the study).

Participants by arm

Arm	Count
Part 1: Placebo 1 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.	403
Part 1: Otilimab 90 mg 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.	403
Part 2: Placebo 2 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.	175
Part 2: Otilimab 90 mg 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.	175
Total	1,156

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Part 1 (Up to Day 60)	Lost to Follow-up	4	8	0	0
Part 1 (Up to Day 60)	Physician Decision	2	5	0	0
Part 1 (Up to Day 60)	Protocol Violation	2	3	0	0
Part 1 (Up to Day 60)	Withdrawal by Subject	7	8	0	0
Part 2 (Up to Day 60)	Lost to Follow-up	0	0	3	2
Part 2 (Up to Day 60)	Physician Decision	0	0	1	1
Part 2 (Up to Day 60)	Withdrawal by Subject	0	0	1	1

Baseline characteristics

Characteristic	Part 1: Placebo 1	Part 1: Otilimab 90 mg	Part 2: Placebo 2	Part 2: Otilimab 90 mg	Total
Age, Customized <18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized >=65 to 84 years	154 Participants	153 Participants	168 Participants	168 Participants	643 Participants
Age, Customized >=85 years	0 Participants	0 Participants	7 Participants	7 Participants	14 Participants
Age, Customized Between 18 to 64 years	249 Participants	250 Participants	0 Participants	0 Participants	499 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	24 Participants	30 Participants	3 Participants	8 Participants	65 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	42 Participants	31 Participants	1 Participants	0 Participants	74 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	4 Participants	4 Participants	0 Participants	0 Participants	8 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	15 Participants	14 Participants	13 Participants	5 Participants	47 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	12 Participants	8 Participants	1 Participants	0 Participants	21 Participants
Race/Ethnicity, Customized Black or African American	25 Participants	26 Participants	6 Participants	6 Participants	63 Participants
Race/Ethnicity, Customized Mixed Asian Race	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Mixed White Race	1 Participants	1 Participants	1 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Multiple	7 Participants	7 Participants	0 Participants	0 Participants	14 Participants
Race/Ethnicity, Customized Unknown	11 Participants	9 Participants	0 Participants	1 Participants	21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	27 Participants	21 Participants	14 Participants	21 Participants	83 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	235 Participants	251 Participants	136 Participants	134 Participants	756 Participants
Sex: Female, Male Female	128 Participants	101 Participants	75 Participants	73 Participants	377 Participants
Sex: Female, Male Male	275 Participants	302 Participants	100 Participants	102 Participants	779 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	93 / 403	84 / 403	76 / 175	74 / 175
other Total, other adverse events	97 / 396	115 / 397	57 / 173	51 / 174
serious Total, serious adverse events	147 / 396	124 / 397	90 / 173	90 / 174

Outcome results

Primary

Part 1: Percentage of Participants Alive and Free of Respiratory Failure 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.

Time frame: At Day 28

Population: 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	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28	67 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28	71 Percentage of participants

p-value: 0.045695% CI: [0.96, 1.82]Regression, Logistic

Primary

Part 2: Percentage of Participants Alive and Free of Respiratory Failure 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.

Time frame: At Day 28

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28	51 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28	52 Percentage of participants

p-value: 0.857495% CI: [0.67, 1.61]Regression, Logistic

Secondary

Part 1: Number of Participants Who Died Due to All Causes at Day 60

Number of participants who died due to all causes at Day 60 are reported.

Time frame: At Day 60

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Placebo 1	Part 1: Number of Participants Who Died Due to All Causes at Day 60	93 Participants
Part 1: Otilimab 90 mg	Part 1: Number of Participants Who Died Due to All Causes at Day 60	84 Participants

p-value: 0.205795% CI: [0.61, 1.22]Regression, Logistic

Secondary

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)

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

Population: Safety population comprised of all participants who received study intervention

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Placebo 1	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)	Non-SAEs	67 Participants
Part 1: Placebo 1	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)	SAEs	147 Participants
Part 1: Otilimab 90 mg	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)	Non-SAEs	91 Participants
Part 1: Otilimab 90 mg	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)	SAEs	124 Participants

Secondary

Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28

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

Population: 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	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28	29 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28	16 Percentage of participants

p-value: 0.011995% CI: [0.18, 0.89]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14

Time frame: At Day 14

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14	61 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14	63 Percentage of participants

p-value: 0.175495% CI: [0.85, 1.58]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42

Time frame: At Day 42

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42	70 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42	74 Percentage of participants

p-value: 0.061695% CI: [0.93, 1.79]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60

Time frame: At Day 60

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60	74 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60	75 Percentage of participants

p-value: 0.18395% CI: [0.84, 1.63]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7

Time frame: At Day 7

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7	42 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7	44 Percentage of participants

p-value: 0.287195% CI: [0.8, 1.49]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen 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.

Time frame: At Day 14

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14	37 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14	37 Percentage of participants

p-value: 0.390195% CI: [0.77, 1.42]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28

Time frame: At Day 28

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28	57 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28	57 Percentage of participants

p-value: 0.476395% CI: [0.75, 1.36]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42

Time frame: At Day 42

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42	63 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42	66 Percentage of participants

p-value: 0.197395% CI: [0.84, 1.56]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60

Time frame: At Day 60

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60	67 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60	71 Percentage of participants

p-value: 0.117395% CI: [0.88, 1.67]Regression, Logistic

Secondary

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7

Time frame: At Day 7

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7	11 Percentage of participants
Part 1: Otilimab 90 mg	Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7	12 Percentage of participants

p-value: 0.281495% CI: [0.73, 1.8]Regression, Logistic

Secondary

Part 1: Time to Death Due to All Causes 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.

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to Death Due to All Causes up to Day 60	NA Days
Part 1: Otilimab 90 mg	Part 1: Time to Death Due to All Causes up to Day 60	NA Days

p-value: 0.194295% CI: [0.65, 1.18]Regression, Cox

Secondary

Part 1: Time to Final ICU Discharge

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

Population: 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	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to Final ICU Discharge	13 Days
Part 1: Otilimab 90 mg	Part 1: Time to Final ICU Discharge	15 Days

p-value: 0.440495% CI: [0.83, 1.24]Regression, Cox

Secondary

Part 1: Time to First Discharge From Investigator Site 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.

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to First Discharge From Investigator Site up to Day 60	18 Days
Part 1: Otilimab 90 mg	Part 1: Time to First Discharge From Investigator Site up to Day 60	18 Days

p-value: 0.107895% CI: [0.94, 1.3]Regression, Cox

Secondary

Part 1: 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.

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60	21 Days
Part 1: Otilimab 90 mg	Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60	20 Days

p-value: 0.11495% CI: [0.94, 1.31]Regression, Cox

Secondary

Part 1: Time to Last Dependence on Supplementary Oxygen

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

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to Last Dependence on Supplementary Oxygen	22 Days
Part 1: Otilimab 90 mg	Part 1: Time to Last Dependence on Supplementary Oxygen	21 Days

p-value: 0.42595% CI: [0.85, 1.23]Regression, Cox

Secondary

Part 1: Time to Recovery From Respiratory Failure 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.

Time frame: Up to Day 28

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 1: Time to Recovery From Respiratory Failure up to Day 28	10 Days
Part 1: Otilimab 90 mg	Part 1: Time to Recovery From Respiratory Failure up to Day 28	9 Days

p-value: 0.095995% CI: [0.95, 1.32]Regression, Cox

Secondary

Part 2: Number of Participants Who Died Due to All Causes at Day 28

Number of participants who died due to all causes at Day 28 is reported

Time frame: At Day 28

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Placebo 1	Part 2: Number of Participants Who Died Due to All Causes at Day 28	70 Participants
Part 1: Otilimab 90 mg	Part 2: Number of Participants Who Died Due to All Causes at Day 28	63 Participants

p-value: 0.306195% CI: [0.5, 1.24]Regression, Logistic

Secondary

Part 2: Number of Participants Who Died Due to All Causes at Day 60

Number of participants who died due to all causes at Day 60 is reported

Time frame: At Day 60

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Placebo 1	Part 2: Number of Participants Who Died Due to All Causes at Day 60	76 Participants
Part 1: Otilimab 90 mg	Part 2: Number of Participants Who Died Due to All Causes at Day 60	74 Participants

p-value: 0.666595% CI: [0.59, 1.41]Regression, Logistic

Secondary

Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs

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

Population: Safety population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Placebo 1	Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs	Non-SAEs	57 Participants
Part 1: Placebo 1	Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs	SAEs	90 Participants
Part 1: Otilimab 90 mg	Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs	Non-SAEs	50 Participants
Part 1: Otilimab 90 mg	Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs	SAEs	90 Participants

Secondary

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14

Time frame: At Day 14

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14	43 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14	49 Percentage of participants

p-value: 0.255795% CI: [0.83, 2]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42

Time frame: At Day 42

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42	54 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42	54 Percentage of participants

p-value: 0.85695% CI: [0.67, 1.61]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60

Time frame: At Day 60

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60	55 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60	56 Percentage of participants

p-value: 0.753395% CI: [0.69, 1.66]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7

Time frame: At Day 7

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7	28 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7	37 Percentage of participants

p-value: 0.083195% CI: [0.95, 2.39]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14

Time frame: At Day 14

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14	23 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14	28 Percentage of participants

p-value: 0.358195% CI: [0.77, 2.06]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28

Time frame: At Day 28

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28	39 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28	38 Percentage of participants

p-value: 0.962195% CI: [0.63, 1.54]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42

Time frame: At Day 42

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42	46 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42	41 Percentage of participants

p-value: 0.416795% CI: [0.54, 1.29]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60

Time frame: At Day 60

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60	51 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60	46 Percentage of participants

p-value: 0.340895% CI: [0.53, 1.25]Regression, Logistic

Secondary

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7

Time frame: At Day 7

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

Arm	Measure	Value (NUMBER)
Part 1: Placebo 1	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7	3 Percentage of participants
Part 1: Otilimab 90 mg	Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7	13 Percentage of participants

p-value: 0.003795% CI: [1.57, 10.13]Regression, Logistic

Secondary

Part 2: Time to Death Due to All Causes up to Day 60

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to Death Due to All Causes up to Day 60	NA Days
Part 1: Otilimab 90 mg	Part 2: Time to Death Due to All Causes up to Day 60	NA Days

p-value: 0.532495% CI: [0.65, 1.24]Regression, Cox

Secondary

Part 2: Time to Final ICU Discharge

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

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to Final ICU Discharge	NA Days
Part 1: Otilimab 90 mg	Part 2: Time to Final ICU Discharge	NA Days

p-value: 0.625395% CI: [0.72, 1.72]Regression, Cox

Secondary

Part 2: Time to First Discharge From Investigator Site 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.

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to First Discharge From Investigator Site up to Day 60	36 Days
Part 1: Otilimab 90 mg	Part 2: Time to First Discharge From Investigator Site up to Day 60	37 Days

p-value: 0.708495% CI: [0.8, 1.4]Regression, Cox

Secondary

Part 2: Time to First Discharge to Non-hospitalized Residence

Time frame: Up to Day 60

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to First Discharge to Non-hospitalized Residence	NA Days
Part 1: Otilimab 90 mg	Part 2: Time to First Discharge to Non-hospitalized Residence	53 Days

p-value: 0.408595% CI: [0.84, 1.52]Regression, Cox

Secondary

Part 2: Time to Last Dependence on Supplementary Oxygen

Time frame: Up to Day 28

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to Last Dependence on Supplementary Oxygen	NA Days
Part 1: Otilimab 90 mg	Part 2: Time to Last Dependence on Supplementary Oxygen	NA Days

p-value: 0.477495% CI: [0.81, 1.59]Regression, Cox

Secondary

Part 2: Time to Recovery From Respiratory Failure up to Day 28

Time frame: Up to Day 28

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

Arm	Measure	Value (MEDIAN)
Part 1: Placebo 1	Part 2: Time to Recovery From Respiratory Failure up to Day 28	24 Days
Part 1: Otilimab 90 mg	Part 2: Time to Recovery From Respiratory Failure up to Day 28	22 Days

p-value: 0.442195% CI: [0.84, 1.5]Regression, Cox

Source: ClinicalTrials.gov · Data processed: Jun 27, 2026

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

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Masking description

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28

Part 1: Number of Participants Who Died Due to All Causes at Day 60

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events (Non-SAEs)

Part 1: Percentage of Participants Admitted to Intensive Care Unit (ICU) up to Day 28

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60

Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60

Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7

Part 1: Time to Death Due to All Causes up to Day 60

Part 1: Time to Final ICU Discharge

Part 1: Time to First Discharge From Investigator Site up to Day 60

Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60

Part 1: Time to Last Dependence on Supplementary Oxygen

Part 1: Time to Recovery From Respiratory Failure up to Day 28

Part 2: Number of Participants Who Died Due to All Causes at Day 28

Part 2: Number of Participants Who Died Due to All Causes at Day 60

Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60

Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60

Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7

Part 2: Time to Death Due to All Causes up to Day 60

Part 2: Time to Final ICU Discharge

Part 2: Time to First Discharge From Investigator Site up to Day 60

Part 2: Time to First Discharge to Non-hospitalized Residence

Part 2: Time to Last Dependence on Supplementary Oxygen

Part 2: Time to Recovery From Respiratory Failure up to Day 28