Clinical Trial Results:
A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab in patients with severe pulmonary COVID-19 related disease
Summary
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EudraCT number |
2020-001759-42 |
Trial protocol |
GB NL ES BE DE IT |
Global end of trial date |
16 Aug 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Mar 2022
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First version publication date |
16 Mar 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
214094
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Sep 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Aug 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy of otilimab intravenous (IV) versus placebo
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Protection of trial subjects |
Not Applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 May 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 102
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Country: Number of subjects enrolled |
Belgium: 21
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Country: Number of subjects enrolled |
Brazil: 31
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Country: Number of subjects enrolled |
Canada: 19
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Country: Number of subjects enrolled |
Chile: 11
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Country: Number of subjects enrolled |
Colombia: 1
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Country: Number of subjects enrolled |
France: 258
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Country: Number of subjects enrolled |
India: 72
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Japan: 48
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Country: Number of subjects enrolled |
Mexico: 48
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Country: Number of subjects enrolled |
Netherlands: 47
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Country: Number of subjects enrolled |
Peru: 12
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Country: Number of subjects enrolled |
Poland: 12
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Country: Number of subjects enrolled |
Russian Federation: 113
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Country: Number of subjects enrolled |
South Africa: 36
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Country: Number of subjects enrolled |
Spain: 94
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
United States: 214
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Worldwide total number of subjects |
1156
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EEA total number of subjects |
439
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
499
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From 65 to 84 years |
643
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85 years and over |
14
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Recruitment
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Recruitment details |
This was a 2-part study evaluating efficacy and safety of intravenously (IV) administered otilimab in participants with severe pulmonary Coronavirus Disease-2019 (COVID-19) related disease. Part 1 consisted of participants aged 18 to 79 years and Part 2 consisted of participants aged 70 years and older. | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 1156 (806 in Part 1 and 350 in Part 2) participants were enrolled in the study (Enrolled Population: All participants who entered the study). | ||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part 1: Placebo 1 | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo 1
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Sterile 0.9% (w/v) sodium chloride solution administered once via IV infusion
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Arm title
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Part 1: Otilimab 90 mg | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Otilimab 90 mg (diluted in sodium chloride solution)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solution in single-use vial (150 mg/milliliters [mL]) diluted in sterile 0.9% (w/v) sodium chloride solution and administered once via IV infusion
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Arm title
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Part 2: Placebo 2 | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo 2
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Sterile 5% (w/v) dextrose solution administered once via IV infusion
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Arm title
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Part 2: Otilimab 90 mg | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Otilimab 90 mg (diluted in dextrose solution)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solution in single-use vial (150 mg/mL) diluted in sterile 5% (w/v) dextrose solution and administered once via IV infusion
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Baseline characteristics reporting groups
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Reporting group title |
Part 1: Placebo 1
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Reporting group description |
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 1: Otilimab 90 mg
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Reporting group description |
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2: Placebo 2
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Reporting group description |
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2: Otilimab 90 mg
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Reporting group description |
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part 1: Placebo 1
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Reporting group description |
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. | ||
Reporting group title |
Part 1: Otilimab 90 mg
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Reporting group description |
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. | ||
Reporting group title |
Part 2: Placebo 2
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Reporting group description |
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. | ||
Reporting group title |
Part 2: Otilimab 90 mg
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Reporting group description |
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care. |
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End point title |
Part 1: Percentage of participants alive and free of respiratory failure at Day 28 [1] | |||||||||
End point description |
Participants were considered alive and free of respiratory failure if they were in category 1,2,3 or 4 from the GSK modified version ordinal scale adapted from World Health Organization (WHO) scale 2020.The 8-point scale was as follows:1)Non-hospitalized,no limitation of activity;2) Non-hospitalized,limitation of activity;3) Hospitalized,no oxygen therapy;4)Hospitalized,low-flow oxygen by mask/nasal prongs;5) Hospitalized,highflow oxygen (>=15 liters per minute),continuous positive airway pressure(CPAP),bilevel positive airway pressure(BIPAP),non-invasive ventilation;6) Hospitalized,intubation and mechanical ventilation;7) Hospitalized,mechanical ventilation plus additional organ support;8)Death.Higher scale indicate higher intensity of respiratory failure. Percentage values are rounded off.Modified intent to treat(mITT) population consisted of all randomized participants who received study intervention.Only those participants with data available at specified timepoints were analyzed
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End point type |
Primary
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End point timeframe |
At Day 28
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Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
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Notes [2] - mITT Population [3] - mITT Population |
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Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
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Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
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Number of subjects included in analysis |
782
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.0456 [4] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.32
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.96 | |||||||||
upper limit |
1.82 | |||||||||
Notes [4] - p-value is from a one-sided test. |
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End point title |
Part 2: Percentage of participants alive and free of respiratory failure at Day 28 [5] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
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End point type |
Primary
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End point timeframe |
At Day 28
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Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
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Notes [6] - mITT Population. [7] - mITT Population. |
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Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
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Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
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Number of subjects included in analysis |
342
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.8574 [8] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.04
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.67 | |||||||||
upper limit |
1.61 | |||||||||
Notes [8] - p-value is generated from a two-sided test. |
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End point title |
Part 1: Number of participants who died due to all causes at Day 60 [9] | |||||||||
End point description |
Number of participants who died due to all causes at Day 60 are reported. Only those participants with data available at the specified time points were analyzed.
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End point type |
Secondary
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End point timeframe |
At Day 60
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Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
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Notes [10] - mITT Population. [11] - mITT Population. |
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Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
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Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
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Number of subjects included in analysis |
759
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.2057 [12] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.86
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.61 | |||||||||
upper limit |
1.22 | |||||||||
Notes [12] - p-value is from a one-sided test. |
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End point title |
Part 2: Number of participants who died due to all causes at Day 28 [13] | |||||||||
End point description |
Number of participants who died due to all causes at Day 28 is reported. Only those participants with data available at the specified time points were analyzed.
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End point type |
Secondary
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End point timeframe |
At Day 28
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Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
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Notes [14] - mITT Population. [15] - mITT Population. |
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Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
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Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
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Number of subjects included in analysis |
342
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.3061 [16] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.79
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.5 | |||||||||
upper limit |
1.24 | |||||||||
Notes [16] - p-value is generated from a two-sided test. |
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End point title |
Part 2: Number of participants who died due to all causes at Day 60 [17] | |||||||||
End point description |
Number of participants who died due to all causes at Day 60 is reported. Only those participants with data available at the specified time points were analyzed.
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End point type |
Secondary
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End point timeframe |
At Day 60
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Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
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Notes [18] - mITT Population. [19] - mITT Population. |
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Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
341
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.6665 [20] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.91
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.59 | |||||||||
upper limit |
1.41 | |||||||||
Notes [20] - p-value is generated from a two-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to death due to all causes up to Day 60 [21] | ||||||||||||
End point description |
Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented. Only those participants with data available at the specified time points were analyzed. 9999 indicates that <25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [22] - mITT Population. [23] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
177
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.1942 [24] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.88
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.65 | ||||||||||||
upper limit |
1.18 | ||||||||||||
Notes [24] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to death due to all causes up to Day 60 [25] | ||||||||||||
End point description |
Time to death due to all causes was defined as the time (days) from dosing to death, due to any cause, up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to death are presented. Only those participants with data available at the specified time points were analyzed. 9999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [26] - mITT Population. [27] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
|
||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
150
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.5324 [28] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.65 | ||||||||||||
upper limit |
1.24 | ||||||||||||
Notes [28] - p-value is generated from a two-sided test |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and free of respiratory failure at Day 7 [29] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 7
|
|||||||||
Notes [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [30] - mITT Population. [31] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
789
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.2871 [32] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.09
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.8 | |||||||||
upper limit |
1.49 | |||||||||
Notes [32] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and free of respiratory failure at Day 14 [33] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 14
|
|||||||||
Notes [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [34] - mITT Population. [35] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
785
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.1754 [36] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.16
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.85 | |||||||||
upper limit |
1.58 | |||||||||
Notes [36] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and free of respiratory failure at Day 42 [37] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 42
|
|||||||||
Notes [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [38] - mITT Population. [39] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
777
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.0616 [40] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.29
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.93 | |||||||||
upper limit |
1.79 | |||||||||
Notes [40] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and free of respiratory failure at Day 60 [41] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 60
|
|||||||||
Notes [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [42] - mITT Population. [43] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
759
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.183 [44] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.17
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.84 | |||||||||
upper limit |
1.63 | |||||||||
Notes [44] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and free of respiratory failure at Day 7 [45] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 7
|
|||||||||
Notes [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [46] - mITT Population. [47] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
347
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.0831 [48] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.51
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.95 | |||||||||
upper limit |
2.39 | |||||||||
Notes [48] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and free of respiratory failure at Day 14 [49] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 14
|
|||||||||
Notes [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [50] - mITT Population. [51] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
345
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.2557 [52] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.29
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.83 | |||||||||
upper limit |
2 | |||||||||
Notes [52] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and free of respiratory failure at Day 42 [53] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 42
|
|||||||||
Notes [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [54] - mITT Population. [55] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
342
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.856 [56] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.04
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.67 | |||||||||
upper limit |
1.61 | |||||||||
Notes [56] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and free of respiratory failure at Day 60 [57] | |||||||||
End point description |
Participants were alive and free of respiratory failure if they were in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Higher scale indicates higher intensity of respiratory failure. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 60
|
|||||||||
Notes [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [58] - mITT Population [59] - mITT Population |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
341
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.7533 [60] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.07
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.69 | |||||||||
upper limit |
1.66 | |||||||||
Notes [60] - p-value is generated from a two-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to recovery from respiratory failure up to Day 28 [61] | ||||||||||||
End point description |
Time to recovery from respiratory failure was defined as time (days) from dosing to last recovery from respiratory failure upto (and including) Day 28.Participants were in respiratory failure if they were in category 5 or above from the GSK modified ordinal scale adapted from WHO scale 2020.The 8-point scale was as follows:1) Non-hospitalized, no limitation of activity;2) Non-hospitalized,limitation of activity;3) Hospitalized, no oxygen therapy;4) Hospitalized, low-flow oxygen by mask/nasal prongs;5)Hospitalized,highflow oxygen(>=15L/min),continuous positive airway pressure (CPAP),bilevel positive airway pressure(BIPAP),non-invasive ventilation;6)Hospitalized, intubation and mechanical ventilation;7)Hospitalized, mechanical ventilation plus additional organ support;8)Death.9999 indicates that <75% participants experienced event within treatment arm. Third-quartile could not be derived. Only those participants with data available at the specified time points were analyzed
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [62] - mITT Population. [63] - mITT Population |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
544
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.0959 [64] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.12
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.95 | ||||||||||||
upper limit |
1.32 | ||||||||||||
Notes [64] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to recovery from respiratory failure up to Day 28 [65] | ||||||||||||
End point description |
Time to recovery from respiratory failure was defined as time (days) from dosing to last recovery from respiratory failure upto (and including) Day 28.Participants were in respiratory failure if they were in category 5 or above from the GSK modified ordinal scale adapted from WHO scale 2020.The 8-point scale was as follows:1) Non-hospitalized,no limitation of activity;2)Non-hospitalized,limitation of activity;3) Hospitalized, no oxygen therapy;4) Hospitalized, low-flow oxygen by mask/nasal prongs;5)Hospitalized,highflow oxygen(>=15L/min),continuous positive airway pressure (CPAP),bilevel positive airway pressure(BIPAP),non-invasive ventilation;6)Hospitalized, intubation and mechanical ventilation;7)Hospitalized, mechanical ventilation plus additional organ support;8)Death.99999 indicates that <75% participants experienced event within treatment arm. Third-quartile could not be derived. Only those participants with data available at the specified time points were analyzed
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [66] - mITT Population [67] - mITT Population |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
|
||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
181
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4421 [68] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.12
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.84 | ||||||||||||
upper limit |
1.5 | ||||||||||||
Notes [68] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 7 [69] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 7
|
|||||||||
Notes [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [70] - mITT Population. [71] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
789
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.2814 [72] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.14
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.73 | |||||||||
upper limit |
1.8 | |||||||||
Notes [72] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 14 [73] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 14
|
|||||||||
Notes [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [74] - mITT Population. [75] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
785
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.3901 [76] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.04
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.77 | |||||||||
upper limit |
1.42 | |||||||||
Notes [76] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 28 [77] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 28
|
|||||||||
Notes [77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [78] - mITT Population. [79] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
782
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.4763 [80] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.01
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.75 | |||||||||
upper limit |
1.36 | |||||||||
Notes [80] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 42 [81] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 42
|
|||||||||
Notes [81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [82] - mITT population. [83] - mITT population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
777
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.1973 [84] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.14
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.84 | |||||||||
upper limit |
1.56 | |||||||||
Notes [84] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants alive and independent of supplementary oxygen at Day 60 [85] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 60
|
|||||||||
Notes [85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [86] - mITT Population. [87] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
759
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.1173 [88] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.21
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.88 | |||||||||
upper limit |
1.67 | |||||||||
Notes [88] - p-value is from a one-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 7 [89] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 7
|
|||||||||
Notes [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [90] - mITT Population. [91] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
347
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.0037 [92] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
3.98
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
1.57 | |||||||||
upper limit |
10.13 | |||||||||
Notes [92] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 14 [93] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 14
|
|||||||||
Notes [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [94] - mITT Population. [95] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
345
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.3581 [96] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
1.26
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.77 | |||||||||
upper limit |
2.06 | |||||||||
Notes [96] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 28 [97] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 28
|
|||||||||
Notes [97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [98] - mITT Population. [99] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
342
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.9621 [100] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.99
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.63 | |||||||||
upper limit |
1.54 | |||||||||
Notes [100] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 42 [101] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 42
|
|||||||||
Notes [101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [102] - mITT Population. [103] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
342
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.4167 [104] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.83
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.54 | |||||||||
upper limit |
1.29 | |||||||||
Notes [104] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 2: Percentage of participants alive and independent of supplementary oxygen at Day 60 [105] | |||||||||
End point description |
Participants were independent of supplementary oxygen if they were in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale was as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized,limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, highflow oxygen (>=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. Percentage values are rounded off. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
At Day 60
|
|||||||||
Notes [105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [106] - mITT Population. [107] - mITT Population. |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, age, and both clinical status at Baseline and sex as randomized. Missing data was imputed with monotone logistic multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
341
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.3408 [108] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.81
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.53 | |||||||||
upper limit |
1.25 | |||||||||
Notes [108] - p-value is generated from a two-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to last dependence on supplementary oxygen [109] | ||||||||||||
End point description |
Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [110] - mITT Population. [111] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
444
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.425 [112] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.85 | ||||||||||||
upper limit |
1.23 | ||||||||||||
Notes [112] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to last dependence on supplementary oxygen [113] | ||||||||||||
End point description |
Time to last dependence on supplementary oxygen was defined as the time (days) from dosing to last dependence on supplementary oxygen up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to last dependence on supplementary oxygen are presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [113] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [114] - mITT Population. [115] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
|
||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
134
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4774 [116] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.81 | ||||||||||||
upper limit |
1.59 | ||||||||||||
Notes [116] - p-value is generated from a two-sided test. |
|
||||||||||
End point title |
Part 1: Percentage of participants admitted to Intensive Care Unit (ICU) up to Day 28 [117] | |||||||||
End point description |
Participants who were admitted to the ICU up to (and including) Day 28 were evaluated. Percentage values are rounded off. mITT Population (not in ICU at Baseline) comprised of participants in the mITT population who were not in the ICU at Baseline. Only those participants with data available at the specified time points were analyzed.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Day 28
|
|||||||||
Notes [117] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||
|
||||||||||
Notes [118] - mITT Population (not in ICU at Baseline) [119] - mITT Population (not in ICU at Baseline) |
||||||||||
Statistical analysis title |
Statistical analysis 1 | |||||||||
Statistical analysis description |
Analysis performed using logistic regression adjusted for treatment, and both clinical status at Baseline and age group as randomized. Missing data was imputed with monotone discriminant multiple imputation assuming data is missing at random.
|
|||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
|||||||||
Number of subjects included in analysis |
193
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
= 0.0119 [120] | |||||||||
Method |
Regression, Logistic | |||||||||
Parameter type |
Odds ratio (OR) | |||||||||
Point estimate |
0.4
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.18 | |||||||||
upper limit |
0.89 | |||||||||
Notes [120] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to final ICU discharge [121] | ||||||||||||
End point description |
Time to final ICU discharge was defined as the time from dosing to when the participant is discharged from the ICU for the last time up to (and including) Day 28. mITT Population admitted to ICU at Baseline comprised of those participants in mITT who were admitted to ICU at Baseline. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [121] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [122] - mITT population admitted to ICU at Baseline. [123] - mITT population admitted to ICU at Baseline. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
600
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4404 [124] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.83 | ||||||||||||
upper limit |
1.24 | ||||||||||||
Notes [124] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to final ICU discharge [125] | ||||||||||||
End point description |
Time to final ICU discharge was defined as the time from dosing to when the participant was discharged from the ICU for the last time up to (and including) Day 28. Median and inter-quartile range (first quartile and third quartile) of time to final ICU discharge is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 28
|
||||||||||||
Notes [125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [126] - mITT population admitted to ICU at Baseline. [127] - mITT population admitted to ICU at Baseline. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
|
||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
82
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.6253 [128] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.72 | ||||||||||||
upper limit |
1.72 | ||||||||||||
Notes [128] - p-value is generated from a two-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to first discharge from investigator site up to Day 60 [129] | ||||||||||||
End point description |
Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site (IS) up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [130] - mITT Population. [131] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
582
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.1078 [132] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.94 | ||||||||||||
upper limit |
1.3 | ||||||||||||
Notes [132] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 1: Time to first discharge to non-hospitalized residence up to Day 60 [133] | ||||||||||||
End point description |
Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge to non-hospitalized residence is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [133] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [134] - mITT Population. [135] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized and age group as randomized.
|
||||||||||||
Comparison groups |
Part 1: Placebo 1 v Part 1: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
549
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.114 [136] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.94 | ||||||||||||
upper limit |
1.31 | ||||||||||||
Notes [136] - p-value is from a one-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to first discharge from investigator site up to Day 60 [137] | ||||||||||||
End point description |
Time to first discharge from investigator site was defined as the time (days) from dosing to when the participant was first discharged from investigator site up to (and including) Day 60. Median and inter-quartile range (first quartile and third quartile) of time to first discharge from investigator site is presented. Only those participants with data available at the specified time points were analyzed. 99999 indicates that <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [138] - mITT Population. [139] - mITT Population. |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
195
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [140] | ||||||||||||
P-value |
= 0.7084 [141] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.8 | ||||||||||||
upper limit |
1.4 | ||||||||||||
Notes [140] - Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age. [141] - p-value is generated from a two-sided test. |
|
|||||||||||||
End point title |
Part 2: Time to first discharge to non-hospitalized residence [142] | ||||||||||||
End point description |
Time to first discharge to non-hospitalized residence was defined as the time (days) from dosing to when the participant (parti) was discharged to a non-hospitalized residence for the first time up to (and including) Day 60. Only those participants with data available at the specified time points were analyzed. In Part 2: Placebo 2 arm, 99999 indicates that <50% participants experienced event within treatment arm. Hence, median and third-quartile could not be derived. In Part 2: Otilimab 90 mg arm, 99999 indicates that <75%participants experienced event within the treatment arm. Hence, third-quartile could not be derived.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 60
|
||||||||||||
Notes [142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
|||||||||||||
|
|||||||||||||
Notes [143] - mITT Population [144] - mITT Population |
|||||||||||||
Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Model adjusted analysis performed using a Cox proportional hazards model adjusted by treatment, clinical status at Baseline as randomized, sex as randomized and age.
|
||||||||||||
Comparison groups |
Part 2: Placebo 2 v Part 2: Otilimab 90 mg
|
||||||||||||
Number of subjects included in analysis |
176
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.4085 [145] | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.13
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.84 | ||||||||||||
upper limit |
1.52 | ||||||||||||
Notes [145] - p-value is generated from a two-sided test. |
|
||||||||||||||||
End point title |
Part 1: Number of participants with serious adverse events (SAEs) and common (>=5%) non-serious adverse events (non-SAEs) [146] | |||||||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented. Safety population comprised of all participants who received study intervention.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to Day 60
|
|||||||||||||||
Notes [146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||||||||
|
||||||||||||||||
Notes [147] - Safety Population [148] - Safety Population |
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Part 2: Number of participants with SAEs and common (>=5%) non-SAEs [149] | |||||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Number of participants with any SAE and common (>=5%) non-SAEs are presented.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to Day 60
|
|||||||||||||||
Notes [149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoints are described part-wise; whereas the Baseline characteristics are for overall study. |
||||||||||||||||
|
||||||||||||||||
Notes [150] - Safety Population [151] - Safety Population |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All-cause mortality, SAEs, and non-SAEs were collected up to Day 60 in Part 1 and 2 of the study
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
SAEs and non-serious AEs were reported for Safety Population (all participants who received study intervention). All-cause mortality was reported for Enrolled population(all participants who entered the study).Sixteen participants from Enrolled Population(N=1156) did not receive study treatment, hence were not included in Safety Population(N=1140)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Part 1: Placebo 1
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)79 years received blinded 1-hour IV infusion of placebo (sterile 0.9 percent [%] weight by volume [w/v] sodium chloride solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 1: Otilimab 90 mg
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants between the ages of >=18 years and <=79 years received blinded otilimab 90 milligrams (mg) (solution in single-use vial diluted in sterile 0.9% w/v sodium chloride solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2: Placebo 2
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Reporting group description |
Participants aged 70 years or above received blinded 1-hour IV infusion of placebo (sterile 5% w/v dextrose solution) once along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2: Otilimab 90 mg
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Reporting group description |
Participants aged 70 years or above received blinded otilimab 90 mg (solution in single-use vial diluted in sterile 5% dextrose solution) once as 1-hour IV infusion along with standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 May 2020 |
Amendment 1: Modifications to the protocol in response to regulatory feedback, and clarifications based on investigator feedback. The key change is revision of the primary endpoint (where definition of “free of respiratory failure” is participants in categories 1-4 on GlaxoSmithKline [GSK] Ordinal Scale). Other changes are (1) to revise recording of blood pressure and pulse rate; (2) to add details of randomization caps; (3) to simplify/clarify some Inclusion and Exclusion Criteria; (4) to clarify medications permitted during the study. |
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02 Jul 2020 |
Amendment 2: Modifications to the protocol in response to regulatory and ethics committee feedback, and clarifications based on investigator feedback. The main changes are (1) clarification that Day 1 pre-dose assessments do not need to be repeated if Screening and Randomization are within 24 hours; (2) expedited reporting of cytokine release syndrome (CRS) as an adverse event of special interest (AESI); (3) clarification that organ transplant participants are excluded per Exclusion Criteria #11; (4) clarification of conditions by which convalescent plasma is permitted or not during the study; (5) removed specific mention of chloroquine and hydroxychloroquine; (6) expanded the null hypothesis; (7) consent may be collected before the 48hour screening window. |
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25 Jan 2021 |
Amendment 3: Before the last of 806 participants completed the study (Last Subject Last Visit, Day 60), an interim analysis of the primary endpoint and all-cause mortality data at Day 28 showed that substantial clinical benefit was evident in one of the pre-defined stratification subgroups “Age 70 to less than (<)80 years”, with no safety concerns in any subgroup. Given the ongoing pandemic and particularly high mortality of Coronavirus Disease-2019 (COVID-19) disease in participants over 70 years old, together with recent publications that support the hypothesis that the severity of the disease is driven by a maladaptive innate immune response in which Granulocyte-macrophage colony stimulating factor (GM-CSF) plays a key role and which is more commonly elevated in older participants. GSK has therefore determined to urgently confirm these subgroup findings by amending the protocol to allow the enrolment of an additional cohort of participants aged 70 years and above with no upper age limit. GSK has reviewed the results from what is now considered as the first part of the study (Part 1) and decided that a second part will be added to the study (Part 2) which has less frequent assessments to decrease the burden on sites |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |