Sarilumab COVID-19 | NCT04327388

ID	Type	Description	Link
2020-001162-12	EudraCT Number
U1111-1249-6021	Other Identifier	WHO Universal Trial Reference Number

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Label	Type	Description	Intervention Names
Sarilumab 200 mg	Experimental	Sarilumab 200 milligrams (mg), single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in fraction of inspired oxygen (FiO2) requirement or Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction.	Drug: Sarilumab SAR153191
Sarilumab 400 mg	Experimental	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.	Drug: Sarilumab SAR153191
Placebo	Placebo Comparator	Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Name	Type	Description	Arm Group Labels	Other Names
Sarilumab SAR153191	Drug	Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion	Sarilumab 200 mg Sarilumab 400 mg

Measure	Description	Time Frame
Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points	Time to improvement of greater than or equal (>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of >=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.	Baseline to Day 29

Measure	Description	Time Frame
Percentage of Participants Who Were Alive at Day 29	Percentage of participants who were alive at Day 29 were reported in this outcome measure.	Day 29
Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 0320001		Caba		1430	Argentina
Investigational Site Number 0320003

PubMed Identifier	Type	Citation	Retractions
33676590	Derived	Lescure FX, Honda H, Fowler RA, Lazar JS, Shi G, Wung P, Patel N, Hagino O; Sarilumab COVID-19 Global Study Group. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 May;9(5):522-532. doi: 10.1016/S2213-2600(21)00099-0. Epub 2021 Mar 4.

Label	URL
EFC16844 Plain Language Results Summary	View source

ID	Title	Description
FG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in fraction of inspired oxygen (FiO2) requirement or Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 11, 2020	Apr 28, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points

Time to improvement of greater than or equal (>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of >=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.

Analysis was performed on modified intention-to-treat (mITT) population which included all participants who were treated with study medication and were analyzed according to the initial treatment assigned to the participant (as randomized).

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG002	Placebo	Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Units	Counts
Participants	OG000159 OG001173 OG00284

Title

Denominators

Categories

Title	Measurements
	OG00010.0(9.00 to 12.00) OG00110.0(9.00 to 13.00) OG00212.0(9.00 to 15.00)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Log-rank test	Analyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.	0.9561		Hazard Ratio (HR)	1.026			2-Sided	95	0.751	1.402			Hazard ratio for estimation of treatment effect of each sarilumab dose versus placebo was assessed by cox proportional hazard model stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.		Superiority

Secondary

Percentage of Participants Who Were Alive at Day 29

Percentage of participants who were alive at Day 29 were reported in this outcome measure.

Analysis was performed on mITT population.

Posted

Number

percentage of participants

Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29

Clinical status of participants was assessed using 7-point ordinal scale ranges from: 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score=less severity. Percentage of participants With >=1 point improvement in clinical status from Baseline at Days 4, 7, 15, 21, and 29 (assessed using the 7-point ordinal scale) were reported.

Analysis was performed on mITT population.

Posted

Number

percentage of participants

Baseline, Days 4, 7, 15, 21, and 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score

Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.

Posted

Mean

Standard Deviation

scores on a scale

Baseline, Days 4, 7, 15, 21, and 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg

Secondary

Time to Resolution of Fever

Resolution of fever was defined as body temperature less than or equal to (<=) 36.6 degree Celsius (°C) (axilla), or <=37.2°C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics/until discharge, whichever was sooner. Time to resolution of fever (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever) - date of first dose + 1. Kaplan-Meier method was used for estimation.

Analysis was performed on mITT population.

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Time to Resolution of Fever and Improvement in Oxygenation

Time to resolution of fever was defined as body temperature <=36.6°C (axilla), or <=37.2 °C (oral), or <=37.8°C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge, whichever was sooner. Improvement in oxygenation was defined as oxygen saturation (SpO2)/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to resolution of fever and improvement in oxygenation (in days) was calculated as: date of first occurrence/episode of the event (resolution of fever and improvement in oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.

Analysis was performed on mITT population.

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg

Secondary

Number of Days With Fever

Fever was defined as body temperature greater than (>) 37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period. Number of days with fever were reported. Least square (LS) mean and standard error (SE) were estimated using the analysis of covariance (ANCOVA) model with treatment group and randomization strata as fixed effects.

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Posted

Least Squares Mean

Standard Error

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29

NEWS2: used to standardize assessment of acute-illness severity, track clinical condition of participants and to alert clinical teams to participant deterioration. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. Percentage of participants in following clinical risk categories were reported: low risk (score 0 to 4); low to medium risk (score of 3 in any individual parameter); medium risk (score 5 to 6); high risk (score 7 to 19).

Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Posted

Number

percentage of participants

Baseline, Days 4, 7, 15, 21, and 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours

Time to NEWS2 <2 and maintained for 24 hours: time (in days) from 1st dose of study drug until 1st occurrence of NEWS score of <2 (maintained for 24 hours); calculated as: date of 1st occurrence/episode of event (NEWS score of <2) - date of 1st dose + 1. NEWS2 score was based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (score of 0 or 1 was allocated) and level of consciousness (score of 0 or 3 was allocated), where 0=normal health condition to 3=worst health condition; higher score=more severity. All scores were summed to get an aggregate score which ranged from 0 to 19, with higher scores=more severity/higher risk. Kaplan-Meier method was used for analysis.

Analysis was performed on mITT population.

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2

The NEWS2 was used to standardize the assessment of acute-illness severity, track the clinical condition of participants, and to alert clinical teams to participant deterioration. NEWS2 score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, and temperature. A score of 0, 1, 2, and 3 was allocated to each parameter except supplemental oxygen (a score of 0 or 1 was allocated) and level of consciousness (a score of 0 or 3 was allocated), where 0 = normal health condition to 3 = worst health condition; higher score indicated more severity. All scores were summed to get an aggregate score. Aggregate NEWS2 score ranged from 0 to 19, with higher scores meaning more severity/higher risk. LS means and SE were estimated using ANCOVA model with treatment group and randomization strata as fixed effects, and baseline NEWS2 score as a covariate.

Posted

Least Squares Mean

Standard Error

scores on a scale

Baseline, Days 4, 7, 15, 21, and 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Time-to-improvement in Oxygenation

Time-to-improvement in oxygenation was defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours or until discharge, whichever was sooner. Nadir SpO2/FiO2 was the nadir (lowest value) at any point in the study. Time to improvement in oxygenation was calculated as: date of first occurrence/episode of the event (oxygenation) - date of first dose + 1. Kaplan-Meier method was used for estimation.

Analysis was performed on mITT population.

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants Alive Off Supplemental Oxygen at Day 29

Supplemental oxygen was defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

Analysis was performed on mITT population.

Posted

Number

percentage of participants

Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Days With Hypoxemia

Hypoxemia (low level of oxygen in the blood) was defined as SpO2 <93% on room air, or required supplemental oxygen, or mechanical ventilatory support. Days meeting the criteria for hypoxemia since the first study dose were counted and the percentage of days with hypoxemia were calculated as:100*number of days with the hypoxemia divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.

Analysis was performed on mITT population.

Posted

Least Squares Mean

Standard Error

percentage of days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Days With Supplemental Oxygen Use

Supplemental oxygen (oxygen therapy) was defined as oxygen administration using oxygen delivery device (e.g. nasal cannula, simple face mask, non-rebreather mask, high flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, extracorporeal life support, etc.). Days meeting the criteria for supplemental oxygen use since the first study dose were counted and the percentage of days with supplemental oxygen use were calculated as:100*number of days with the supplemental oxygen use divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29) . LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.

Analysis was performed on mITT population.

Posted

Least Squares Mean

Standard Error

percentage of days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg

Secondary

Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute

Resting respiratory rate was measured in terms of number of breaths per minute (bpm) while a person is at rest. Only the days with respiratory rate >24 breath per minute since the first dose were counted and percentage of days with respiratory rate > 24 bpm were calculated as:100*number of days with respiratory rate >24 bpm divided by number of days of follow up (defined as the earlier date of death or discharge or last visit up to Day 29). LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.

Analysis was performed on mITT population. Hence, overall number of participants analyzed = participants evaluable for this outcome measure.

Posted

Least Squares Mean

Standard Error

percentage of days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg

Secondary

Time to Oxygen Saturation >= 94% on Room Air

Time to oxygen saturation >=94% on room air was defined as the time (in days) from first dose of study drug until the time of first occurrence of oxygen saturation >=94% and it was calculated as: Date of first occurrence/episode of the event (oxygen saturation >=94%) - date of first dose + 1.Kaplan-Meier method was used for estimation.

Analysis was performed on mITT population.

Posted

Median

95% Confidence Interval

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Mean Number of Ventilator Free Days

Mean number of ventilator free days in participants were reported.

Analysis was performed on mITT population.

Posted

Mean

Standard Deviation

days

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula

Percentage of participants With initiation of mechanical ventilation or non-invasive ventilation, or use of high flow nasal cannula were reported in this outcome measure.

Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.

Posted

Number

percentage of participants

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants Who Required Rescue Medication

Rescue medications were defined as the immunosuppressive (methylprednisolone, dexamethasone and prednisone) therapies. During the course of the study, participant who required rescue therapy was based on the judgement of the study physician.

Analysis was performed on mITT population.

Posted

Number

percentage of participants

Baseline to Day 28

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study

Percentage of participants who needed ICU care until Day 29 were reported for those not in an ICU at baseline.

Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Posted

Number

percentage of participants

Baseline to Day 29

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Days of Hospitalization Among Survivors (Alive Participants)

Number of days of hospitalization among alive participants were counted at Day 60 since the first dose. LS mean and SE were estimated using the ANCOVA model with treatment group and randomization strata as fixed effects.

Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.

Posted

Least Squares Mean

Standard Error

days

At Day 60

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Treatment-emergent AEs (TEAEs) were the AEs that developed or worsened or became serious during the TEAE period (from the time of first dose of study drug to the last dose of study drug + 60 days). SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event.

Analysis was performed on safety population which included all randomized participants who were treated with the study medication and were analyzed according to the actual treatment received.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Major or Opportunistic Bacterial or Fungal Infections

Major or opportunistic bacterial or fungal infections was considered as an adverse event of special interest (AESI: defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).

Analysis was performed on safety population.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection

Grade 4 neutropenia was defined as participants with absolute neutrophil count (ANC) <500 per cubic millimeter (mm^3). Grade 4 neutropenia with concurrent invasive infection was defined as infections and infestations (in participants with Grade 4 neutropenia) within 1 week of ANC <500/mm^3 and was considered as an AESI (defined as an AE [serious or non-serious] of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required).

Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category and "0" in the number analyzed field signifies that no participants had Grade 4 neutropenia and therefore were not evaluable.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation

Grade >=2 (moderate) infusion related reactions (defined as any TEAE signs or symptoms experienced by participants who received study medication within 24 hours of the start of infusion) and Grade >=2 (moderate) hypersensitivity reactions (anaphylactic reaction, hypersensitivity or angioedema and moderate reactions) were considered as AESI which was defined as an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required. Gastrointestinal Perforation was defined as formation of a hole through the stomach, large bowel or small intestine.

Analysis was performed on safety population.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001

Secondary

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets

Criteria for PCSA:

Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (male) and <=95 g/L (female); greater than or equal to (>=) 185 g/L (male) and >=165 g/L (female); and decrease from baseline >=20 g/L.
Leukocytes: <3.0*10^9/Liters (L) (Non-Black) or <2.0*10^9/L (black); >=16.0*10^9/L.
Platelets: < 100*10^9/L; >=700*10^9/L.

Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters

Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline; >= 100% change from baseline.

Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Secondary

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

Alanine Aminotransferase (ALT): >3 upper limit of normal (ULN); >5 ULN; >10 ULN and >20 ULN.
Bilirubin: >1.5 ULN; >2 ULN.

Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Posted

Count of Participants

Participants

Baseline up to 60 days

ID	Title	Description
OG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
OG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Blood Loss Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0013 events3 affected173 at risk EG0020 events0 affected84 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0023 events3 affected84 at risk
Cardiac Arrest	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Intracardiac Thrombus	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Pulseless Electrical Activity	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Ventricular Tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Entropion	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Gastric Ulcer Perforation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Intra-Abdominal Haematoma	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Megacolon	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Death	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Hyperthermia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected159 at risk EG0013 events3 affected173 at risk EG0023 events3 affected84 at risk
Physical Deconditioning	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Sudden Death	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Hepatic Steatosis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hepatitis Acute	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hepatocellular Injury	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Abscess Limb	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Bacterial Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0022 events2 affected84 at risk
Covid-19 Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG00011 events11 affected159 at risk EG0014 events4 affected173 at risk EG0022 events2 affected84 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Cystitis Klebsiella	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Endocarditis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Lower Respiratory Tract Infection Fungal	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Peritonitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0016 events6 affected173 at risk EG0020 events0 affected84 at risk
Pneumonia Bacterial	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0013 events3 affected173 at risk EG0021 events1 affected84 at risk
Pneumonia Klebsiella	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Septic Shock	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected159 at risk EG0015 events4 affected173 at risk EG0022 events2 affected84 at risk
Soft Tissue Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Staphylococcal Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Systemic Bacterial Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0012 events2 affected173 at risk EG0020 events0 affected84 at risk
Systemic Candida	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0012 events2 affected173 at risk EG0020 events0 affected84 at risk
Tracheobronchitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected159 at risk EG0013 events3 affected173 at risk EG0021 events1 affected84 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Brain Oedema	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Carotid Artery Thrombosis	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Hydrocephalus	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Hypoxic-Ischaemic Encephalopathy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected159 at risk EG0014 events4 affected173 at risk EG0020 events0 affected84 at risk
Renal Failure	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0012 events2 affected173 at risk EG0020 events0 affected84 at risk
Renal Impairment	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0014 events4 affected173 at risk EG0020 events0 affected84 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Organising Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Pneumothorax Spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0012 events2 affected173 at risk EG0022 events2 affected84 at risk
Respiratory Arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0006 events6 affected159 at risk EG0015 events5 affected173 at risk EG0023 events3 affected84 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Hypertensive Crisis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Peripheral Artery Occlusion	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0011 events1 affected173 at risk EG0020 events0 affected84 at risk
Thrombophlebitis Superficial	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Vena Cava Thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected159 at risk EG0010 events0 affected173 at risk EG0021 events1 affected84 at risk
Venous Thrombosis Limb	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected159 at risk EG0010 events0 affected173 at risk EG0020 events0 affected84 at risk

ID	Term
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Title	Description
BG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
BG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
BG002	Placebo	Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sarilumab 200 mg	Sarilumab 200 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.	17	159	42	159	57	159
EG001	Sarilumab 400 mg	Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.	18	173	51	173	68	173
EG002	Placebo	Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 [dated 08-Apr-2020]): Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and Increase/recurrence of fever or Increase/no change in FiO2 requirement or Required vasopressors, ECMO or development of multi-organ dysfunction.	9	84	20	84	14	84