Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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.
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 : July 15, 2021
Actual Study Completion Date : August 16, 2021


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.




Primary Outcome Measures :
  1. Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 28 [ Time Frame: 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.

  2. Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 28 [ Time Frame: 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 :
  1. Part 1: Number of Participants Who Died Due to All Causes at Day 60 [ Time Frame: At Day 60 ]
    Number of participants who died due to all causes at Day 60 are reported.

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

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

  4. Part 1: Time to Death Due to All Causes up to Day 60 [ Time Frame: 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.

  5. Part 2: Time to Death Due to All Causes up to Day 60 [ Time Frame: 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.

  6. Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 7 [ Time Frame: 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.

  7. Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 14 [ Time Frame: 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.

  8. Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 42 [ Time Frame: 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.

  9. Part 1: Percentage of Participants Alive and Free of Respiratory Failure at Day 60 [ Time Frame: 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.

  10. Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 7 [ Time Frame: 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.

  11. Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 14 [ Time Frame: 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.

  12. Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 42 [ Time Frame: 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.

  13. Part 2: Percentage of Participants Alive and Free of Respiratory Failure at Day 60 [ Time Frame: 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.

  14. Part 1: Time to Recovery From Respiratory Failure up to Day 28 [ Time Frame: 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.

  15. Part 2: Time to Recovery From Respiratory Failure up to Day 28 [ Time Frame: 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.

  16. Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7 [ Time Frame: 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.

  17. Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14 [ Time Frame: 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.

  18. Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28 [ Time Frame: 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.

  19. Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42 [ Time Frame: 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.

  20. Part 1: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60 [ Time Frame: 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.

  21. Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 7 [ Time Frame: 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.

  22. Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 14 [ Time Frame: 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.

  23. Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 28 [ Time Frame: 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.

  24. Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 42 [ Time Frame: 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.

  25. Part 2: Percentage of Participants Alive and Independent of Supplementary Oxygen at Day 60 [ Time Frame: 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.

  26. Part 1: Time to Last Dependence on Supplementary Oxygen [ Time Frame: 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.

  27. Part 2: Time to Last Dependence on Supplementary Oxygen [ Time Frame: 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.

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

  29. Part 1: Time to Final ICU Discharge [ Time Frame: 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.

  30. Part 2: Time to Final ICU Discharge [ Time Frame: 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.

  31. Part 1: Time to First Discharge From Investigator Site up to Day 60 [ Time Frame: 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.

  32. Part 1: Time to First Discharge to Non-hospitalized Residence up to Day 60 [ Time Frame: 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.

  33. Part 2: Time to First Discharge From Investigator Site up to Day 60 [ Time Frame: 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.

  34. Part 2: Time to First Discharge to Non-hospitalized Residence [ Time Frame: 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.

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

  36. Part 2: Number of Participants With SAEs and Common (>=5%) Non-SAEs [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04376684


Locations
Show Show 120 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] January 25, 2021
Statistical Analysis Plan  [PDF] June 3, 2021

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04376684    
Other Study ID Numbers: 214094
First Posted: May 6, 2020    Key Record Dates
Results First Posted: March 9, 2022
Last Update Posted: March 23, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
COVID-19
Otilimab
Ordinal scale
Coronavirus
GSK3196165
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases