Sarilumab COVID-19

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT04327388
Collaborator
Regeneron Pharmaceuticals (Industry)
420
Enrollment
47
Locations
3
Arms
5.2
Actual Duration (Months)
8.9
Patients Per Site
1.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the clinical efficacy of sarilumab relative to the control arm in adult participants hospitalized with severe or critical Coronavirus Disease 2019 (COVID-19).

Secondary Objectives:
  • Evaluate the 28-day survival rate.

  • Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity.

  • Evaluate changes in the National Early Warning Score 2.

  • Evaluate the duration of predefined symptoms and signs (if applicable).

  • Evaluate the duration of supplemental oxygen dependency (if applicable).

  • Evaluate the incidence of new mechanical ventilation use during the study.

  • Evaluate the duration of new mechanical ventilation use during the Study.

  • Evaluate the proportion of participants requiring rescue medication during the 28-day period.

  • Evaluate need for admission into intensive care unit.

  • Evaluate duration of hospitalization (days).

  • The secondary safety objectives of the study were to evaluate the safety of sarilumab through hospitalization (up to Day 29 if participant was still hospitalized) compared to the control arm as assessed by incidence of:

  • Serious adverse events.

  • Major or opportunistic bacterial or fungal infections in participants with grade 4 neutropenia.

  • Grade greater than or equal to (>=) 2 infusion related reactions.

  • Grade >=2 hypersensitivity reactions.

  • Increase in alanine transaminase (ALT) >=3X upper limit of normal (ULN) (for participants with normal baseline) or greater than 3X ULN AND at least 2-fold increase from baseline value (for participants with abnormal baseline).

  • Major or opportunistic bacterial or fungal infections.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Sarilumab SAR153191
  • Drug: Placebo
Phase 3

Detailed Description

An individual participant would complete the study approximately 60 days from screening to follow-up on day 60 ±7 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
420 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19
Actual Study Start Date :
Mar 28, 2020
Actual Primary Completion Date :
Jul 31, 2020
Actual Study Completion Date :
Sep 2, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Sarilumab 200 mg

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
Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
Other Names:
  • REGN88
  • Kevzara®
  • Experimental: 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.

    Drug: Sarilumab SAR153191
    Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
    Other Names:
  • REGN88
  • Kevzara®
  • Placebo Comparator: 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.

    Drug: Placebo
    Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion

    Outcome Measures

    Primary Outcome Measures

    1. Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points [Baseline to Day 29]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants Who Were Alive at Day 29 [Day 29]

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

    2. 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 [Baseline, 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.

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

    4. Time to Resolution of Fever [Baseline to Day 29]

      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.

    5. Time to Resolution of Fever and Improvement in Oxygenation [Baseline to Day 29]

      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.

    6. Number of Days With Fever [Baseline to Day 29]

      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.

    7. 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 [Baseline, 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).

    8. Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours [Baseline to Day 29]

      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.

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

      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.

    10. Time-to-improvement in Oxygenation [Baseline to Day 29]

      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.

    11. Percentage of Participants Alive Off Supplemental Oxygen at Day 29 [Day 29]

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

    12. Percentage of Days With Hypoxemia [Baseline to Day 29]

      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.

    13. Percentage of Days With Supplemental Oxygen Use [Baseline to Day 29]

      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.

    14. Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute [Baseline to Day 29]

      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.

    15. Time to Oxygen Saturation >= 94% on Room Air [Baseline to Day 29]

      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.

    16. Mean Number of Ventilator Free Days [Baseline to Day 29]

      Mean number of ventilator free days in participants were reported.

    17. Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula [Baseline to Day 29]

      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.

    18. Percentage of Participants Who Required Rescue Medication [Baseline to Day 28]

      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.

    19. Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study [Baseline to Day 29]

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

    20. Number of Days of Hospitalization Among Survivors (Alive Participants) [At Day 60]

      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.

    21. Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [Baseline up to 60 days]

      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.

    22. Number of Participants With Major or Opportunistic Bacterial or Fungal Infections [Baseline up to 60 days]

      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).

    23. Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection [Baseline up to 60 days]

      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).

    24. Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation [Baseline up to 60 days]

      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.

    25. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets [Baseline up to 60 days]

      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.

    26. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters [Baseline up to 60 days]

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

    27. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters [Baseline up to 60 days]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria :

    Participants must be >=18 years of age. Participants must be hospitalized for less than or equal to 7 days with evidence of pneumonia and have one of the following disease categories: severe disease or critical disease.

    Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.

    Exclusion criteria:

    Unlikely to survive after 48 hours from screening or unlikely to remain at the investigational site beyond 48 hours. Participants with multi organ dysfunction or requiring extracorporeal life support or renal replacement therapy were excluded.

    Presence of neutropenia less than 2000/cubic millimeter (mmˆ3), aspartate transaminase or ALT greater than 5X ULN, platelets less than 50,000/mmˆ3.

    Prior immunosuppressive therapies. Use of systemic chronic corticosteroids for non-COVID-19 related condition. Known or suspected history of tuberculosis. Suspected or known active systemic bacterial or fungal infections.

    The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Investigational Site Number 0320001CabaArgentina1430
    2Investigational Site Number 0320003CabaArgentinaC1180AAX
    3Investigational Site Number 0320004CabaArgentinaC1426AAM
    4Investigational Site Number 0760003Porto AlegreBrazil90110-270
    5Investigational Site Number 0760001Sao PauloBrazil01327-001
    6Investigational Site Number 0760002Sao PauloBrazil04231-030
    7Investigational Site Number 0760004São José Do Rio PretoBrazil15090-000
    8Investigational Site Number 0760005São PauloBrazil04321-120
    9Investigational Site Number 1240001MontrealCanadaH2X3E4
    10Investigational Site Number 1240005MontrealCanadaH4A 3J1
    11Investigational Site Number 1240004TorontoCanadaM4N3M5
    12Investigational Site Number 1240002TorontoCanadaM5G 2N2
    13Investigational Site Number 1240003VancouverCanadaV5Z 1M9
    14Investigational Site Number 1520003SantiagoChile750-0691
    15Investigational Site Number 1520002SantiagoChile80004005
    16Investigational Site Number 1520004SantiagoChile
    17Investigational Site Number 1520001TalcaChile3460001
    18Investigational Site Number 2500001Bordeaux CedexFrance33076
    19Investigational Site Number 2500007ClamartFrance92140
    20Investigational Site Number 2500006La Roche Sur Yon Cedex 9France85925
    21Investigational Site Number 2500002NantesFrance44093
    22Investigational Site Number 2500005Paris Cedex 18France75877
    23Investigational Site Number 2500003StrasbourgFrance67098
    24Investigational Site Number 2500004SuresnesFrance92151
    25Investigational Site Number 2760002EssenGermany45147
    26Investigational Site Number 2760004KölnGermany50937
    27Investigational Site Number 2760001MünsterGermany48149
    28Investigational site number 3760003AshdodIsrael7747629
    29Investigational Site Number 3760002JerusalemIsrael91120
    30Investigational Site Number 3760001Ramat GanIsrael52662
    31Investigational Site Number 3800005MilanoItaly20122
    32Investigational Site Number 3800001MilanoItaly20132
    33Investigational Site Number 3800002MilanoItaly20157
    34Investigational Site Number 3800003ModenaItaly41100
    35Investigational Site Number 3800004ParmaItaly43100
    36Investigational Site Number 3800006RozzanoItaly20089
    37Investigational Site Number 3920002Fuchu-ShiJapan
    38Investigational Site Number 3920003Iruma-GunJapan
    39Investigational Site Number 3920001Kamakura-ShiJapan
    40Investigational Site Number 6430003MoscowRussian Federation111539
    41Investigational Site Number 6430002MoscowRussian Federation123182
    42Investigational Site Number 6430001MoscowRussian Federation129301
    43Investigational Site Number 7240003BarcelonaSpain08035
    44Investigational Site Number 7240004BarcelonaSpain08036
    45Investigational Site Number 7240002MadridSpain28007
    46Investigational Site Number 7240005MadridSpain28034
    47Investigational Site Number 7240001MadridSpain28046

    Sponsors and Collaborators

    • Sanofi
    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Sciences & Operations, Sanofi

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT04327388
    Other Study ID Numbers:
    • EFC16844
    • 2020-001162-12
    • U1111-1249-6021
    First Posted:
    Mar 31, 2020
    Last Update Posted:
    Mar 17, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsStudy was conducted at 46 active centers in 11 countries. A total of 431 participants were screened between 28 March 2020 and 02 July 2020, of which 10 participants were screen failures and 1 participant was randomized twice and thus excluded. Therefore, a total of 420 participants were randomized in the study treatment by the interactive response technology (IRT) (2:2:1 ratio) to receive sarilumab 200 milligrams (mg)/400 mg and placebo. Screen failures were mainly due to exclusion criteria met.
    Pre-assignment DetailRandomization was stratified by severity of illness (severe disease, critical disease) and use of systemic corticosteroids (Yes/No).
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Period Title: Overall Study
    STARTED16117386
    Treated15917384
    Participants Who Received Second Dose13115
    COMPLETED14115375
    NOT COMPLETED202011

    Baseline Characteristics

    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlaceboTotal
    Arm/Group DescriptionSarilumab 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.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.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.Total of all reporting groups
    Overall Participants16117386420
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.3
    (13.7)
    58.0
    (14.1)
    59.9
    (14.8)
    58.5
    (14.1)
    Sex: Female, Male (Count of Participants)
    Female
    52
    32.3%
    74
    42.8%
    30
    34.9%
    156
    37.1%
    Male
    109
    67.7%
    99
    57.2%
    56
    65.1%
    264
    62.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    1.2%
    2
    1.2%
    1
    1.2%
    5
    1.2%
    Asian
    5
    3.1%
    9
    5.2%
    6
    7%
    20
    4.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    1
    1.2%
    1
    0.2%
    Black or African American
    3
    1.9%
    5
    2.9%
    1
    1.2%
    9
    2.1%
    White
    128
    79.5%
    128
    74%
    69
    80.2%
    325
    77.4%
    More than one race
    0
    0%
    3
    1.7%
    0
    0%
    3
    0.7%
    Unknown or Not Reported
    23
    14.3%
    26
    15%
    8
    9.3%
    57
    13.6%
    Clinical Status: 7-point ordinal scale (Count of Participants)
    Scale Score 1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Scale Score 2
    17
    10.6%
    24
    13.9%
    10
    11.6%
    51
    12.1%
    Scale Score 3
    28
    17.4%
    21
    12.1%
    11
    12.8%
    60
    14.3%
    Scale Score 4
    113
    70.2%
    128
    74%
    65
    75.6%
    306
    72.9%
    Scale Score 5
    3
    1.9%
    0
    0%
    0
    0%
    3
    0.7%
    Scale Score 6
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Scale Score 7
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleTime to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points
    DescriptionTime 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.
    Time FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    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).
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    10.0
    10.0
    12.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sarilumab 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.9561
    Comments
    MethodLog-rank test
    CommentsAnalyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.026
    Confidence Interval (2-Sided) 95%
    0.751 to 1.402
    Parameter Dispersion Type:
    Value:
    Estimation CommentsHazard 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.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sarilumab 400 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.3376
    Comments
    MethodLog-rank test
    CommentsAnalyzed based on logrank test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.135
    Confidence Interval (2-Sided) 95%
    0.835 to 1.543
    Parameter Dispersion Type:
    Value:
    Estimation CommentsHazard 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.
    2. Secondary Outcome
    TitlePercentage of Participants Who Were Alive at Day 29
    DescriptionPercentage of participants who were alive at Day 29 were reported in this outcome measure.
    Time FrameDay 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Number [percentage of participants]
    89.9
    55.8%
    91.9
    53.1%
    91.7
    106.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sarilumab 200 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.6280
    Comments
    MethodCochran-Mantel-Haenszel
    CommentsBy Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
    Method of EstimationEstimation ParameterDifference in percentage
    Estimated Value-1.7
    Confidence Interval (2-Sided) 95%
    -9.27 to 5.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sarilumab 400 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.8478
    Comments
    MethodCochran-Mantel-Haenszel
    CommentsBy Cochran-Mantel-Haenszel test stratified by severity of illness (severe, critical) and use of systemic corticosteroids (Yes, No) as entered in IRT.
    Method of EstimationEstimation ParameterDifference in percentage
    Estimated Value0.2
    Confidence Interval (2-Sided) 95%
    -6.93 to 7.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    TitlePercentage 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
    DescriptionClinical 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 FrameBaseline, Days 4, 7, 15, 21, and 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Day 4
    25.2
    15.7%
    25.4
    14.7%
    23.8
    27.7%
    Day 7
    51.6
    32%
    48.6
    28.1%
    42.9
    49.9%
    Day 15
    74.8
    46.5%
    76.9
    44.5%
    71.4
    83%
    Day 21
    80.5
    50%
    81.5
    47.1%
    85.7
    99.7%
    Day 29
    84.9
    52.7%
    84.4
    48.8%
    88.1
    102.4%
    4. Secondary Outcome
    TitleChange From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score
    DescriptionClinical 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 FrameBaseline, Days 4, 7, 15, 21, and 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Day 4
    0.1
    (0.9)
    0.1
    (1.0)
    0.2
    (0.9)
    Day 7
    0.7
    (1.5)
    0.7
    (1.6)
    0.7
    (1.4)
    Day 15
    1.9
    (1.8)
    2.0
    (1.9)
    1.7
    (1.8)
    Day 21
    2.3
    (1.9)
    2.3
    (1.9)
    2.5
    (1.7)
    Day 29
    2.5
    (1.9)
    2.5
    (1.9)
    2.7
    (1.6)
    5. Secondary Outcome
    TitleTime to Resolution of Fever
    DescriptionResolution 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    8.0
    9.0
    7.0
    6. Secondary Outcome
    TitleTime to Resolution of Fever and Improvement in Oxygenation
    DescriptionTime 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    9.0
    10.0
    8.0
    7. Secondary Outcome
    TitleNumber of Days With Fever
    DescriptionFever 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants14315977
    Least Squares Mean (Standard Error) [days]
    1.2
    (0.23)
    1.3
    (0.21)
    1.8
    (0.30)
    8. Secondary Outcome
    TitlePercentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29
    DescriptionNEWS2: 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 FrameBaseline, Days 4, 7, 15, 21, and 29

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15916984
    Baseline: Low
    28.8
    17.9%
    22.1
    12.8%
    34.2
    39.8%
    Baseline: Low to Medium
    0
    0%
    0
    0%
    0
    0%
    Baseline: Medium
    34.2
    21.2%
    37.4
    21.6%
    27.8
    32.3%
    Baseline: High
    37.0
    23%
    40.5
    23.4%
    38.0
    44.2%
    Day 4: Low
    52.8
    32.8%
    56.2
    32.5%
    40.5
    47.1%
    Day 4: Low to Medium
    0.6
    0.4%
    1.2
    0.7%
    0
    0%
    Day 4: Medium
    19.5
    12.1%
    16.6
    9.6%
    28.6
    33.3%
    Day 4: High
    27.0
    16.8%
    26.0
    15%
    31.0
    36%
    Day 7: Low
    57.0
    35.4%
    60.8
    35.1%
    51.4
    59.8%
    Day 7: Low to Medium
    0
    0%
    2.1
    1.2%
    0
    0%
    Day 7: Medium
    20.0
    12.4%
    10.5
    6.1%
    20.3
    23.6%
    Day 7: High
    23.0
    14.3%
    26.6
    15.4%
    28.4
    33%
    Day 15: Low
    52.5
    32.6%
    52.2
    30.2%
    61.1
    71%
    Day 15: Low to Medium
    0
    0%
    1.5
    0.9%
    2.8
    3.3%
    Day 15: Medium
    21.3
    13.2%
    19.4
    11.2%
    13.9
    16.2%
    Day 15: High
    26.2
    16.3%
    26.9
    15.5%
    22.2
    25.8%
    Day 21: Low
    44.8
    27.8%
    50.0
    28.9%
    66.7
    77.6%
    Day 21: Low to Medium
    13.8
    8.6%
    0
    0%
    0
    0%
    Day 21: Medium
    24.1
    15%
    21.1
    12.2%
    8.3
    9.7%
    Day 21: High
    17.2
    10.7%
    28.9
    16.7%
    25.0
    29.1%
    Day 29: Low
    57.1
    35.5%
    27.8
    16.1%
    60.0
    69.8%
    Day 29: Low to Medium
    0
    0%
    0
    0%
    0
    0%
    Day 29: Medium
    14.3
    8.9%
    27.8
    16.1%
    20.0
    23.3%
    Day 29: High
    28.6
    17.8%
    44.4
    25.7%
    20.0
    23.3%
    9. Secondary Outcome
    TitleTime to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours
    DescriptionTime 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    9.0
    9.0
    11.0
    10. Secondary Outcome
    TitleChange From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2
    DescriptionThe 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 FrameBaseline, Days 4, 7, 15, 21, and 29

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants14615979
    Day 4
    -1.07
    (0.212)
    -1.25
    (0.198)
    -0.36
    (0.274)
    Day 7
    -1.63
    (0.265)
    -1.47
    (0.245)
    -0.83
    (0.338)
    Day 15
    -2.10
    (0.508)
    -1.83
    (0.467)
    -2.36
    (0.641)
    Day 21
    -3.02
    (0.769)
    -2.24
    (0.676)
    -2.96
    (1.090)
    Day 29
    -2.57
    (0.936)
    -1.27
    (0.884)
    -3.64
    (1.508)
    11. Secondary Outcome
    TitleTime-to-improvement in Oxygenation
    DescriptionTime-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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    6.0
    6.0
    7.0
    12. Secondary Outcome
    TitlePercentage of Participants Alive Off Supplemental Oxygen at Day 29
    DescriptionSupplemental oxygen was defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
    Time FrameDay 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Number [percentage of participants]
    84.9
    52.7%
    83.8
    48.4%
    86.9
    101%
    13. Secondary Outcome
    TitlePercentage of Days With Hypoxemia
    DescriptionHypoxemia (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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Least Squares Mean (Standard Error) [percentage of days]
    73.01
    (2.063)
    75.10
    (1.941)
    76.32
    (2.724)
    14. Secondary Outcome
    TitlePercentage of Days With Supplemental Oxygen Use
    DescriptionSupplemental 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Least Squares Mean (Standard Error) [percentage of days]
    70.57
    (2.082)
    73.30
    (1.959)
    73.23
    (2.748)
    15. Secondary Outcome
    TitlePercentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute
    DescriptionResting 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Hence, overall number of participants analyzed = participants evaluable for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15016478
    Least Squares Mean (Standard Error) [percentage of days]
    14.74
    (1.582)
    14.58
    (1.485)
    15.74
    (2.105)
    16. Secondary Outcome
    TitleTime to Oxygen Saturation >= 94% on Room Air
    DescriptionTime 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Median (95% Confidence Interval) [days]
    8.0
    8.0
    8.0
    17. Secondary Outcome
    TitleMean Number of Ventilator Free Days
    DescriptionMean number of ventilator free days in participants were reported.
    Time FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Mean (Standard Deviation) [days]
    23.8
    (9.4)
    24.0
    (8.8)
    24.9
    (8.6)
    18. Secondary Outcome
    TitlePercentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula
    DescriptionPercentage 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 FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants12714168
    Number [percentage of participants]
    20.5
    12.7%
    23.4
    13.5%
    19.1
    22.2%
    19. Secondary Outcome
    TitlePercentage of Participants Who Required Rescue Medication
    DescriptionRescue 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 FrameBaseline to Day 28

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Number [percentage of participants]
    13.8
    8.6%
    15.0
    8.7%
    22.6
    26.3%
    20. Secondary Outcome
    TitlePercentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study
    DescriptionPercentage of participants who needed ICU care until Day 29 were reported for those not in an ICU at baseline.
    Time FrameBaseline to Day 29

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants9811456
    Number [percentage of participants]
    11.2
    7%
    14.9
    8.6%
    12.5
    14.5%
    21. Secondary Outcome
    TitleNumber of Days of Hospitalization Among Survivors (Alive Participants)
    DescriptionNumber 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 FrameAt Day 60

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on mITT population. Here, "overall number of participants analyzed"=participants evaluable for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants14215575
    Least Squares Mean (Standard Error) [days]
    15.6
    (0.96)
    16.1
    (0.91)
    15.9
    (1.27)
    22. Secondary Outcome
    TitleNumber of Participants With Treatment-emergent Serious Adverse Events (SAEs)
    DescriptionAn 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 FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Count of Participants [Participants]
    42
    26.1%
    51
    29.5%
    20
    23.3%
    23. Secondary Outcome
    TitleNumber of Participants With Major or Opportunistic Bacterial or Fungal Infections
    DescriptionMajor 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 FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Count of Participants [Participants]
    8
    5%
    15
    8.7%
    3
    3.5%
    24. Secondary Outcome
    TitleNumber of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection
    DescriptionGrade 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 FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Grade 4 neutropenia
    3
    1.9%
    6
    3.5%
    0
    0%
    Grade 4 neutropenia with concurrent invasive infection
    0
    0%
    0
    0%
    25. Secondary Outcome
    TitleNumber of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation
    DescriptionGrade >=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 FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15917384
    Grade >=2 Infusion related reactions
    1
    0.6%
    6
    3.5%
    0
    0%
    Grade >=2 Hypersensitivity reactions
    1
    0.6%
    7
    4%
    0
    0%
    Gastrointestinal perforation
    1
    0.6%
    0
    0%
    0
    0%
    26. Secondary Outcome
    TitleNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets
    DescriptionCriteria 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 FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15617084
    Hemoglobin <=115 g/L (male) and <=95 g/L (female)
    29
    18%
    34
    19.7%
    15
    17.4%
    Hemoglobin >=185 g/L (male) and >=165 g/L (female)
    0
    0%
    0
    0%
    0
    0%
    Hemoglobin decrease from baseline >=20 g/L
    32
    19.9%
    30
    17.3%
    15
    17.4%
    Leukocytes <3.0*10^9/L (Non-Black) or <2.0*10^9/L (black)
    19
    11.8%
    31
    17.9%
    1
    1.2%
    Leukocytes >=16*10^9/L
    13
    8.1%
    21
    12.1%
    6
    7%
    Platelets <100*10^9/L
    2
    1.2%
    7
    4%
    3
    3.5%
    Platelets >=700*10^9/L
    3
    1.9%
    2
    1.2%
    2
    2.3%
    27. Secondary Outcome
    TitleNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
    DescriptionCriteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline; >= 100% change from baseline.
    Time FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15617084
    Creatinine >=150 mcmol/L
    15
    9.3%
    15
    8.7%
    5
    5.8%
    >=30% change from baseline in Creatinine
    31
    19.3%
    30
    17.3%
    10
    11.6%
    >=100% change from baseline in Creatinine
    6
    3.7%
    7
    4%
    3
    3.5%
    28. Secondary Outcome
    TitleNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
    DescriptionAlanine Aminotransferase (ALT): >3 upper limit of normal (ULN); >5 ULN; >10 ULN and >20 ULN. Bilirubin: >1.5 ULN; >2 ULN.
    Time FrameBaseline up to 60 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    Measure Participants15616984
    ALT >3 ULN
    60
    37.3%
    63
    36.4%
    24
    27.9%
    ALT >5 ULN
    28
    17.4%
    25
    14.5%
    12
    14%
    ALT >10 ULN
    6
    3.7%
    5
    2.9%
    3
    3.5%
    ALT >20 ULN
    1
    0.6%
    0
    0%
    0
    0%
    Bilirubin >1.5 ULN
    5
    3.1%
    4
    2.3%
    4
    4.7%
    Bilirubin >2 ULN
    4
    2.5%
    2
    1.2%
    2
    2.3%

    Adverse Events

    Time FrameAll AEs were collected from the time of first dose of study drug up to 60 days regardless of seriousness or relationship to study drug.
    Adverse Event Reporting Description Reported AEs and deaths were TEAEs that developed/worsened in grade or became serious during 'treatment-emergent adverse event period' (from the time of first dose of study drug to the last dose of study drug + 60 days). Analysis was performed on safety population.
    Arm/Group TitleSarilumab 200 mgSarilumab 400 mgPlacebo
    Arm/Group DescriptionSarilumab 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.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.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.
    All Cause Mortality
    Sarilumab 200 mgSarilumab 400 mgPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total17/159 (10.7%) 18/173 (10.4%) 9/84 (10.7%)
    Serious Adverse Events
    Sarilumab 200 mgSarilumab 400 mgPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total42/159 (26.4%) 51/173 (29.5%) 20/84 (23.8%)
    Blood and lymphatic system disorders
    Anaemia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Blood Loss Anaemia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Leukopenia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Neutropenia1/159 (0.6%) 13/173 (1.7%) 30/84 (0%) 0
    Thrombocytopenia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Cardiac disorders
    Atrial Fibrillation0/159 (0%) 00/173 (0%) 03/84 (3.6%) 3
    Cardiac Arrest1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Cardio-Respiratory Arrest1/159 (0.6%) 11/173 (0.6%) 10/84 (0%) 0
    Intracardiac Thrombus1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Pulseless Electrical Activity0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Ventricular Tachycardia1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Eye disorders
    Entropion0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Gastrointestinal disorders
    Dysphagia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Gastric Ulcer Perforation1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Intra-Abdominal Haematoma0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Megacolon0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    General disorders
    Death0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Hyperthermia0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Multiple Organ Dysfunction Syndrome2/159 (1.3%) 23/173 (1.7%) 33/84 (3.6%) 3
    Physical Deconditioning1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Sudden Death0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Hepatobiliary disorders
    Cholelithiasis1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Hepatic Steatosis0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Hepatitis1/159 (0.6%) 11/173 (0.6%) 10/84 (0%) 0
    Hepatitis Acute0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Hepatocellular Injury1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Infections and infestations
    Abscess Limb0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Bacterial Infection0/159 (0%) 01/173 (0.6%) 12/84 (2.4%) 2
    Covid-19 Pneumonia11/159 (6.9%) 114/173 (2.3%) 42/84 (2.4%) 2
    Clostridium Difficile Colitis0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Cystitis Klebsiella0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Endocarditis0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Lower Respiratory Tract Infection Fungal0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Peritonitis1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Pneumonia1/159 (0.6%) 16/173 (3.5%) 60/84 (0%) 0
    Pneumonia Bacterial1/159 (0.6%) 13/173 (1.7%) 31/84 (1.2%) 1
    Pneumonia Klebsiella1/159 (0.6%) 10/173 (0%) 01/84 (1.2%) 1
    Sepsis0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Septic Shock4/159 (2.5%) 44/173 (2.3%) 52/84 (2.4%) 2
    Soft Tissue Infection0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Staphylococcal Sepsis0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Systemic Bacterial Infection0/159 (0%) 02/173 (1.2%) 20/84 (0%) 0
    Systemic Candida0/159 (0%) 02/173 (1.2%) 20/84 (0%) 0
    Tracheobronchitis0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Injury, poisoning and procedural complications
    Ankle Fracture1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Femur Fracture1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Infusion Related Reaction0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Investigations
    Alanine Aminotransferase Increased4/159 (2.5%) 43/173 (1.7%) 31/84 (1.2%) 1
    Metabolism and nutrition disorders
    Hyperkalaemia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Hypertriglyceridaemia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Hyponatraemia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Musculoskeletal and connective tissue disorders
    Rhabdomyolysis1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Nervous system disorders
    Brain Oedema1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Carotid Artery Thrombosis0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Cerebrovascular Accident1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Hydrocephalus1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Hypoxic-Ischaemic Encephalopathy1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Ischaemic Stroke2/159 (1.3%) 21/173 (0.6%) 10/84 (0%) 0
    Renal and urinary disorders
    Acute Kidney Injury2/159 (1.3%) 24/173 (2.3%) 40/84 (0%) 0
    Renal Failure0/159 (0%) 02/173 (1.2%) 20/84 (0%) 0
    Renal Impairment0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure0/159 (0%) 04/173 (2.3%) 40/84 (0%) 0
    Hypoxia0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Organising Pneumonia0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Pneumomediastinum1/159 (0.6%) 10/173 (0%) 01/84 (1.2%) 1
    Pneumothorax0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Pneumothorax Spontaneous0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Pulmonary Embolism1/159 (0.6%) 12/173 (1.2%) 22/84 (2.4%) 2
    Respiratory Arrest1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Respiratory Distress0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Respiratory Failure6/159 (3.8%) 65/173 (2.9%) 53/84 (3.6%) 3
    Vascular disorders
    Deep Vein Thrombosis1/159 (0.6%) 11/173 (0.6%) 10/84 (0%) 0
    Hypertensive Crisis1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Hypotension0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Peripheral Artery Occlusion0/159 (0%) 01/173 (0.6%) 10/84 (0%) 0
    Thrombophlebitis Superficial0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Vena Cava Thrombosis0/159 (0%) 00/173 (0%) 01/84 (1.2%) 1
    Venous Thrombosis Limb1/159 (0.6%) 10/173 (0%) 00/84 (0%) 0
    Other (Not Including Serious) Adverse Events
    Sarilumab 200 mgSarilumab 400 mgPlacebo
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total57/159 (35.8%) 68/173 (39.3%) 14/84 (16.7%)
    Blood and lymphatic system disorders
    Neutropenia11/159 (6.9%) 1113/173 (7.5%) 130/84 (0%) 0
    Investigations
    Alanine Aminotransferase Increased48/159 (30.2%) 4858/173 (33.5%) 5914/84 (16.7%) 14
    Aspartate Aminotransferase Increased11/159 (6.9%) 1115/173 (8.7%) 160/84 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

    Results Point of Contact

    Name/TitleTrial Transparency Team
    OrganizationSanofi
    Phone800-633-1610 ext 6#
    EmailContact-US@sanofi.com
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT04327388
    Other Study ID Numbers:
    • EFC16844
    • 2020-001162-12
    • U1111-1249-6021
    First Posted:
    Mar 31, 2020
    Last Update Posted:
    Mar 17, 2022
    Last Verified:
    Mar 1, 2022