Sarilumab COVID-19

Percentage of Participants Who Were Alive at Day 29

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

Time frame: 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

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.

Time frame: Baseline, Days 4, 7, 15, 21, and 29

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

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.

Time frame: Baseline, Days 4, 7, 15, 21, and 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

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).

Time frame: Baseline, Days 4, 7, 15, 21, and 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline, Days 4, 7, 15, 21, and 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Day 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

Mean Number of Ventilator Free Days

Mean number of ventilator free days in participants were reported.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 29

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.

Time frame: Baseline to Day 28

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.

Time frame: Baseline to Day 29

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.

Time frame: At Day 60

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.

Time frame: Baseline up to 60 days

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).

Time frame: Baseline up to 60 days

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).

Time frame: Baseline up to 60 days

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.

Time frame: Baseline up to 60 days

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.

Time frame: Baseline up to 60 days

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.

Time frame: Baseline up to 60 days

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.

Time frame: Baseline up to 60 days