Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19

An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19

Phase 2:

The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata.

Phase 3 Cohort 1:

The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline.

Phase 3 Cohort 2:

The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Sarilumab; Drug: Placebo

Detailed Description

Phase 2 and Phase 3 Cohort 1 completed. Cohorts 2 and 3 terminated early based on Phase 3 Cohort 1 results.

• Study Type: Interventional
• Enrollment (Actual): 1912
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Regeneron Study Site
    • Sacramento, California, United States, 95817
      • Regeneron Study Site
    • Santa Monica, California, United States, 90404
      • Regeneron Study Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Regeneron Study Site
    • Denver, Colorado, United States, 80206
      • Regeneron Study Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Regeneron Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Regeneron Study Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Regeneron Study Site
    • Orlando, Florida, United States, 32803
      • Regeneron Study Site
    • Tampa, Florida, United States, 33606
      • Regeneron Study Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Regeneron Study Site
    • Decatur, Georgia, United States, 30033
      • Regeneron Study Site
    • Marietta, Georgia, United States, 30060
      • Regeneron Study Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Regeneron Study Site
    • Chicago, Illinois, United States, 60611
      • Regeneron Study Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Regeneron Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Regeneron Study Site
    • Boston, Massachusetts, United States, 02111
      • Regeneron Study Site
    • Boston, Massachusetts, United States, 02215
      • Regeneron Study Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Regeneron Study Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Regeneron Study Site
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • Regeneron Study Site
    • Hackensack, New Jersey, United States, 07601
      • Regeneron Study Site
    • Livingston, New Jersey, United States, 07039
      • Regeneron Study Site
    • Morristown, New Jersey, United States, 07960
      • Regeneron Study Site
    • Neptune, New Jersey, United States, 07753
      • Regeneron Study Site
    • Newark, New Jersey, United States, 07112
      • Regeneron Study Site
    • Teaneck, New Jersey, United States, 07666
      • Regeneron Study Site
  • New York
    • Bronx, New York, United States, 10451
      • Regeneron Study Site
    • Bronx, New York, United States, 10461
      • Regeneron Study Site 1
    • Bronx, New York, United States, 10461
      • Regeneron Study Site 2
    • Bronx, New York, United States, 10467
      • Regeneron Study Site
    • Brooklyn, New York, United States, 11219
      • Regeneron Study Site
    • Buffalo, New York, United States, 14263
      • Regeneron Study Site
    • Elmhurst, New York, United States, 11373
      • Regeneron Study Site
    • Manhasset, New York, United States, 11030
      • Regeneron Study Site 1
    • Manhasset, New York, United States, 11030
      • Regeneron Study Site 2
    • New York, New York, United States, 10029
      • Regeneron Study Site
    • New York, New York, United States, 10032
      • Regeneron Study Site
    • New York, New York, United States, 10016
      • Regeneron Study Site
    • New York, New York, United States, 10065
      • Regeneron Study Site
    • New York, New York, United States, 10003
      • Regeneron Study Site
    • New York, New York, United States, 10037
      • Regeneron Study Site
    • New York, New York, United States, 10025
      • Regeneron Study Site 1
    • New York, New York, United States, 10025
      • Regeneron Study Site 2
    • New York, New York, United States, 10075
      • Regeneron Study Site
    • Stony Brook, New York, United States, 11794
      • Regeneron Study Site
    • Valhalla, New York, United States, 10595
      • Regeneron Study Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Regeneron Study Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Regeneron Study Site
    • Portland, Oregon, United States, 97213
      • Regeneron Study Site
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Regeneron Study Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Regeneron Study Site
    • Scranton, Pennsylvania, United States, 18510
      • Regeneron Study Site
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Regeneron Study Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Regeneron Study Site
    • Dallas, Texas, United States, 75390
      • Regeneron Study Site
  • Utah
    • Murray, Utah, United States, 84107
      • Regeneron Study Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Regeneron Study Site
    • Richmond, Virginia, United States, 23298
      • Regeneron Study Site
  • Washington
    • Everett, Washington, United States, 98201
      • Regeneron Study Site
    • Renton, Washington, United States, 98055
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), result from any specimen (or other commercial or public health assay) within 2 weeks prior to randomization and no alternative explanation for current clinical condition
• Hospitalized with illness of any duration with evidence of pneumonia, requires supplemental oxygen and/or assisted ventilation and meets one of the following:
• Phase 2 and Phase 3 Cohort 1:

Meets 1 of the following criteria at baseline:

• Severe disease OR
• Critical disease OR
• Multi-system organ dysfunction OR
• Immunocompromised
• Phase 3 Cohort 2:

Patients must be receiving mechanical ventilation to treat respiratory failure due to COVID-19

• Phase 3 Cohort 3:

Patients must be receiving supplemental oxygen to treat hypoxemia delivered by one of the following devices:

• Non-rebreather mask, OR
• High-flow device with at least 50% FiO2, OR
• Non-invasive positive pressure ventilator
• Ability to provide informed consent signed by study patient or legally acceptable representative
• Willingness and ability to comply with study-related procedures/assessments

Key Exclusion Criteria:

• In the opinion of the investigator, not expected to survive for more than 48 hours from screening
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2000 mm3, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN), platelets <50,000 per mm3
• Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with the simultaneous combination of leflunomide and methotrexate
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
• Participation in a double-blind clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit (The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, Emergency Use Authorization (EUA), compassionate use protocol or open-label use is permitted)
• Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
• Known systemic hypersensitivity to sarilumab or the excipients of the drug product
• Phase 3 Cohort 2 and Cohort 3 only:
• Known or suspected history of immunosuppression or immunodeficiency disorder
• Patients who require renal replacement therapy for acute kidney injury at randomization or who required renal replacement therapy within 72 hours prior to randomization
• Patients who have circulatory shock requiring vasopressors at randomization or within 24 hours prior to randomization
• Use of extracorporeal life support (eg, ECMO) or, in the opinion of the investigator, there is a high likelihood that extracorporeal life support will be initiated within 48 hours after randomization

NOTE: Other protocol defined inclusion / exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sarilumab 200mg IV (P2); Phase 2	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration
EXPERIMENTAL: Sarilumab 200mg IV (P3:C1); Phase 3: Cohort 1	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration
EXPERIMENTAL: Sarilumab 400mg IV (P2); Phase 2	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration
EXPERIMENTAL: Sarilumab 400mg IV (P3:C1); Phase 3: Cohort 1	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration
EXPERIMENTAL: Sarilumab 800mg IV (P3:C2); Phase 3: Cohort 2	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration
EXPERIMENTAL: Sarilumab 800mg IV (P3: C3); Phase 3: Cohort 3	Drug: Sarilumab; Single or multiple intravenous (IV) doses of sarilumab. Additional doses may be administered if the patient meets protocol defined criteria.; Other Names: SAR153191; Kevzara®; REGN88; Drug: Placebo; Single or multiple intravenous (IV) doses of placebo to match sarilumab administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in CRP Levels at Day 4 in Participants With Serum IL-6 Level Greater Than the ULN (Phase 2)	Percent Change from Baseline in C-Reactive Protein (CRP) Levels at Day 4 in Participants with Serum Interleukin 6 (IL-6) Level Greater than the Upper Limit of Normal (ULN) Least Squares (LS) means estimate of percent change from baseline at Day 4 (raw scale) for each treatment group is based on the Analysis of Covariance (ANCOVA) model. It is defined as anti-log of the estimate of dependent variable minus 1, i.e., (exp[ln(CRP at day 4/Baseline CRP)]-1. Negative numbers imply improvement in CRP.	Baseline and Day 4
Percentage of Participants With at Least a 1-point Improvement in Clinical Status From Baseline to Day 22 Using the 7-point Ordinal Scale in Participants With Critical COVID-19 Receiving Mechanical Ventilation at Baseline (Phase 3 Cohort 1)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Day 22
Percentage of Participants With at Least 1-point Improvement in Clinical Status Using the 7-point Ordinal Scale in Participants With COVID-19 Receiving Mechanical Ventilation at Baseline (Phase 3 Cohort 2)	The ordinal scale is an assessment of the clinical status of a participant The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With Serum IL-6 Levels Greater Than the Upper Limit of Normal (Phase 2)	Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical participants with serum IL-6 levels greater than the upper limit of normal (ULN). The ordinal scale is an assessment of the clinical status of a patient. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to Day 29
Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With All Serum IL-6 Levels (Phase 2)	Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical participants with all serum IL-6 levels. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to Day 29
Time to Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, in Patients With Documented Fever at Baseline (Phase 2)	Time to resolution of fever for at least 48 hours without antipyretics or until discharge, whichever is sooner, in patients with documented fever ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary) at Baseline. Resolution of fever is defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary).	Up to Day 29
Time to Resolution of Fever for at Least 48 Hours Without Antipyretics by Clinical Severity (Phase 2)	Resolution of fever is defined as body temperature <=36.8 C (axilla or temporal) or<= 37.2 C (oral) or <37.6 C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge. Resolution of fever is defined only in participants with presence of fever at baseline.	Up to day 29
Time to Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, by Baseline IL-6 Levels (Phase 2)	Resolution of fever is defined as body temperature <=36.8 C (axilla or temporal) or<= 37.2 C (oral) or <37.6 C (rectal or tympanic) for at least 48 hours without antipyretics or until discharge, by baseline IL-6 levels. Resolution of fever is defined only in participants with presence of fever at baseline.	Up to Day 29
Time to Improvement in Oxygenation for at Least 48 Hours (Phase 2)	Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2	Up to day 29
Time to Improvement in Oxygenation for at Least 48 Hours by Baseline IL-6 Levels (Phase 2)	Time to Improvement defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2	Up to day 29
Time to Resolution of Fever and Improvement in Oxygenation for at Least 48 Hours (Phase 2)	Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2	Up to day 29
Percentage of Participants in Each Clinical Status Category Using the 7-point Ordinal Scale up to Day 29 (Phase 2)	Percentage of participants in each clinical status category using the 7-point ordinal scale from Baseline (Day 1) up to Day 29. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Days 1, 3, 5, 8, 11, 15 and 29
Time to Discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and Maintained for 24 Hours (Phase 2)	NEWS2 was 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: 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).	Up to day 29
Change From Baseline in NEWS2 Scoring System (Phase 2)	NEWS2 was 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: 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).	Days 3, 5, 8, 11, 15 and 29
Number of Days With Fever (Phase 2)	Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)	Up to Day 29
Percentage of Participants Alive, Off Oxygen (Phase 2)		At Day 29
Number of Days of Resting Respiratory Rate >24 Breaths/Min (Phase 2)		Up to day 29
Number of Days With Hypoxemia (Phase 2)		Up to day 29
Number of Days of Supplemental Oxygen Use (Phase 2)		Up to day 29
Time to Saturation ≥94% on Room Air (Phase 2)		Up to day 29
Number of Ventilator Free Days (Phase 2)	Summary of Ventilator-free days during study in Participants using Invasive Mechanical Ventilation at Baseline	Up to Day 22
Number of Participants Who Initiated Mechanical Ventilation After Baseline (Phase 2)		Up to Day 29
Number of Days in an Intensive Care Unit (ICU) in Participants Who Were Not in ICU at Baseline (Phase 2)		Up to Day 29
Number of Days of Hospitalization Among Survivors (Phase 2)		Up to day 29
Number of Deaths Due to Any Cause	Number of deaths due to any cause (All-Cause Mortality)	Up to day 60
Percentage of Participants With at Least 1-point Improvement in Clinical Status Using the 7-point Ordinal Scale in Participants With Critical COVID-19 (Phase 3 Cohort 1: Critical ITT)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Day 22
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22	Day 22
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical ITT)	Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22	Day 22
Percentage of Participants Who Die (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Percentage of Participants who die through Day 29 and Day 60	Up to Day 29 and Day 60
Percentage of Participants Who Die (Phase 3 Cohort 1: Critical ITT)	Percentage of Participants who die through Day 29 and Day 60	Up to Day 29 and Day 60
Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)	At Day 22
Percentage of Participants With at Least a 2-point Improvement in Clinical Status From Baseline to Day 22 Using the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Percentage of participants with at least a 2-point improvement in clinical status from baseline to Day 22 using the 7-point ordinal scale. The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	At Day 22
Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT)	Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)	At Day 22
Percentage of Participants With at Least a 2-point Improvement in Clinical Status From Baseline to Day 22 Using the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)	Percentage of participants with at least a 2-point improvement in clinical status from baseline to Day 22 using the 7-point ordinal scale. The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	At Day 22
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to day 29
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to day 29
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 2)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to day 29
Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to day 29
Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)	The ordinal scale is an assessment of the clinical status of a participant. The 7-point ordinal scale is as follows: 1. Death; 2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized; higher score = less severity	Up to day 29
Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)		Day 22
Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT)		Day 22
Percentage of Patients Discharged and Alive (Phase 3 Cohort 1)	Percentage of Patients Discharged and Alive at Day 22	At Day 22
Percentage of Participants Discharged and Alive at Day 22 (Phase 3 Cohort 1: Critical ITT)	Percentage of Participants Discharged and Alive at Day 22	At Day 22
Time to Recovery (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)	Up to day 29
Time to Recovery (Phase 3 Cohort 1: Critical ITT)	Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)	Up to day 29
Time to Recovery (Phase 3 Cohort 2)	Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)	Up to day 29
Time to Death (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Phase 3 Cohort 1 Time to Death (All-Cause Mortality)	Up to day 60
Time to Death (Phase 3 Cohort 1: Critical ITT)	Time to Death (All-Cause Mortality)	Up to day 60
Time to Death (Phase 3 Cohort 2)	Time to Death (All-Cause Mortality)	Up to day 60
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)	Days 8, 15, 22 and 29
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical ITT)	Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)	Days 8, 15, 22 and 29
Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1)	Number of days of hospitalization among survivors (Phase 3 Cohort 1)	Days 8, 15, 22 and 29
Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1: Critical ITT)	Number of days of hospitalization among survivors (Phase 3 Cohort 1: Critical ITT population)	Days 8, 15, 22 and 29
Number of Participants With Any Serious Adverse Event		Up to day 60
Number of Participants With Grade 4 Neutropenia (ANC <500/mm3)	Grade 4 Neutropenia defined as Absolute Neutrophil Count (ANC) of less than 500 per cubic millimeter(mm3)	Up to day 60
Number of Participants With Severe or Life-threatening Bacterial, Invasive Fungal, or Opportunistic Infection		Up to day 60
Number of Participants With Grade 4 Neutropenia and Concurrent Invasive Infection		Up to day 60
Number of Participants With Grade >=2 Infusion Related Reactions		Up to day 60
Number of Participants With Grade >=2 Hypersensitivity Reactions		Up to day 60
Number of Participants With Gastrointestinal Perforation		Up to day 60
Mean Observed Leukocyte Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Leukocyte Values Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Hemoglobin Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Hemoglobin Values Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Platelet Count Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Platelet Count Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Total Bilirubin Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Total Bilirubin Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 3)		Days 1, 4, 15 and 29
Mean Observed Creatinine Values Across Study Days (Phase 2)		Days 1, 4, 15 and 29
Mean Observed Creatinine Values Across Study Days (Phase 3)		Days 1, 4, 15 and 29

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Sivapalasingam S, Lederer DJ, Bhore R, Hajizadeh N, Criner G, Hosain R, Mahmood A, Giannelou A, Somersan-Karakaya S, O'Brien MP, Boyapati A, Parrino J, Musser BJ, Labriola-Tompkins E, Ramesh D, Purcell LA, Gulabani D, Kampman W, Waldron A, Ng Gong M, Saggar S, Sperber SJ, Menon V, Stein DK, Sobieszczyk ME, Park W, Aberg JA, Brown SM, Kosmicki JA, Horowitz JE, Ferreira MA, Baras A, Kowal B, Thomas DiCioccio A, Akinlade B, Nivens MC, Braunstein N, Herman GA, Yancopoulos GD, Weinreich DM. Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial. Clin Infect Dis. 2022 Aug 24;75(1):e380-e388. doi: 10.1093/cid/ciac153.
• Boyapati A, Wipperman MF, Ehmann PJ, Hamon S, Lederer DJ, Waldron A, Flanagan JJ, Karayusuf E, Bhore R, Nivens MC, Hamilton JD, Sumner G, Sivapalasingam S. Baseline Severe Acute Respiratory Syndrome Viral Load Is Associated With Coronavirus Disease 2019 Severity and Clinical Outcomes: Post Hoc Analyses of a Phase 2/3 Trial. J Infect Dis. 2021 Dec 1;224(11):1830-1838. doi: 10.1093/infdis/jiab445.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 18, 2020
• Primary Completion (ACTUAL): July 24, 2020
• Study Completion (ACTUAL): September 2, 2020

Study Registration Dates

• First Submitted: March 15, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (ACTUAL): March 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: treatment; COVID-19; coronavirus; IL-6; SARS-COV-2; acute respiratory distress syndrome; sarilumab
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 6R88-COV-2040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No