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

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ClinicalTrials.gov Identifier: NCT04315298
Recruitment Status : Completed
First Posted : March 19, 2020
Results First Posted : September 23, 2021
Last Update Posted : September 23, 2021
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Sarilumab Drug: Placebo Phase 2 Phase 3

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1912 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19
Actual Study Start Date : March 18, 2020
Actual Primary Completion Date : July 24, 2020
Actual Study Completion Date : September 2, 2020


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:
  • Kevzara®
  • REGN88
  • SAR153191

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:
  • Kevzara®
  • REGN88
  • SAR153191

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:
  • Kevzara®
  • REGN88
  • SAR153191

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:
  • Kevzara®
  • REGN88
  • SAR153191

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:
  • Kevzara®
  • REGN88
  • SAR153191

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:
  • Kevzara®
  • REGN88
  • SAR153191

Drug: Placebo
Single or multiple intravenous (IV) doses of placebo to match sarilumab administration




Primary Outcome Measures :
  1. Percent Change From Baseline in CRP Levels at Day 4 in Participants With Serum IL-6 Level Greater Than the ULN (Phase 2) [ Time Frame: Baseline and Day 4 ]
    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.

  2. 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) [ Time Frame: Day 22 ]

    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


  3. 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) [ Time Frame: Day 22 ]

    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



Secondary Outcome Measures :
  1. 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 Frame: Up to Day 29 ]

    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


  2. Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With All Serum IL-6 Levels (Phase 2) [ Time Frame: Up to Day 29 ]

    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


  3. 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 Frame: 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 ≥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).


  4. Time to Resolution of Fever for at Least 48 Hours Without Antipyretics by Clinical Severity (Phase 2) [ Time Frame: Up to day 29 ]

    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.


  5. 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) [ Time Frame: Up to Day 29 ]

    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.


  6. Time to Improvement in Oxygenation for at Least 48 Hours (Phase 2) [ Time Frame: Up to day 29 ]
    Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

  7. Time to Improvement in Oxygenation for at Least 48 Hours by Baseline IL-6 Levels (Phase 2) [ Time Frame: Up to day 29 ]
    Time to Improvement defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

  8. Time to Resolution of Fever and Improvement in Oxygenation for at Least 48 Hours (Phase 2) [ Time Frame: Up to day 29 ]

    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


  9. Percentage of Participants in Each Clinical Status Category Using the 7-point Ordinal Scale up to Day 29 (Phase 2) [ Time Frame: Days 1, 3, 5, 8, 11, 15 and 29 ]

    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


  10. Time to Discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and Maintained for 24 Hours (Phase 2) [ Time Frame: Up to day 29 ]
    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).

  11. Change From Baseline in NEWS2 Scoring System (Phase 2) [ Time Frame: Days 3, 5, 8, 11, 15 and 29 ]
    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).

  12. Number of Days With Fever (Phase 2) [ Time Frame: Up to Day 29 ]
    Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)

  13. Percentage of Participants Alive, Off Oxygen (Phase 2) [ Time Frame: At Day 29 ]
  14. Number of Days of Resting Respiratory Rate >24 Breaths/Min (Phase 2) [ Time Frame: Up to day 29 ]
  15. Number of Days With Hypoxemia (Phase 2) [ Time Frame: Up to day 29 ]
  16. Number of Days of Supplemental Oxygen Use (Phase 2) [ Time Frame: Up to day 29 ]
  17. Time to Saturation ≥94% on Room Air (Phase 2) [ Time Frame: Up to day 29 ]
  18. Number of Ventilator Free Days (Phase 2) [ Time Frame: Up to Day 22 ]
    Summary of Ventilator-free days during study in Participants using Invasive Mechanical Ventilation at Baseline

  19. Number of Participants Who Initiated Mechanical Ventilation After Baseline (Phase 2) [ Time Frame: Up to Day 29 ]
  20. Number of Days in an Intensive Care Unit (ICU) in Participants Who Were Not in ICU at Baseline (Phase 2) [ Time Frame: Up to Day 29 ]
  21. Number of Days of Hospitalization Among Survivors (Phase 2) [ Time Frame: Up to day 29 ]
  22. Number of Deaths Due to Any Cause [ Time Frame: Up to day 60 ]
    Number of deaths due to any cause (All-Cause Mortality)

  23. 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) [ Time Frame: Day 22 ]

    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


  24. Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Day 22 ]
    Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22

  25. Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Day 22 ]
    Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22

  26. Percentage of Participants Who Die (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Up to Day 29 and Day 60 ]
    Percentage of Participants who die through Day 29 and Day 60

  27. Percentage of Participants Who Die (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to Day 29 and Day 60 ]
    Percentage of Participants who die through Day 29 and Day 60

  28. Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: At Day 22 ]
    Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)

  29. 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) [ Time Frame: 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. 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


  30. Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT) [ Time Frame: At Day 22 ]
    Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)

  31. 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) [ Time Frame: 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. 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


  32. 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) [ Time Frame: Up to day 29 ]

    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


  33. Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to day 29 ]

    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


  34. Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 2) [ Time Frame: Up to day 29 ]

    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


  35. Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1) [ Time Frame: Up to day 29 ]

    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


  36. Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to day 29 ]

    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


  37. Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Day 22 ]
  38. Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Day 22 ]
  39. Percentage of Patients Discharged and Alive (Phase 3 Cohort 1) [ Time Frame: At Day 22 ]
    Percentage of Patients Discharged and Alive at Day 22

  40. Percentage of Participants Discharged and Alive at Day 22 (Phase 3 Cohort 1: Critical ITT) [ Time Frame: At Day 22 ]
    Percentage of Participants Discharged and Alive at Day 22

  41. Time to Recovery (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Up to day 29 ]
    Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)

  42. Time to Recovery (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to day 29 ]
    Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)

  43. Time to Recovery (Phase 3 Cohort 2) [ Time Frame: Up to day 29 ]
    Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)

  44. Time to Death (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Up to day 60 ]
    Phase 3 Cohort 1 Time to Death (All-Cause Mortality)

  45. Time to Death (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to day 60 ]
    Time to Death (All-Cause Mortality)

  46. Time to Death (Phase 3 Cohort 2) [ Time Frame: Up to day 60 ]
    Time to Death (All-Cause Mortality)

  47. Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline) [ Time Frame: Days 8, 15, 22 and 29 ]
    Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)

  48. Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Days 8, 15, 22 and 29 ]
    Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)

  49. Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1) [ Time Frame: Days 8, 15, 22 and 29 ]
    Number of days of hospitalization among survivors (Phase 3 Cohort 1)

  50. Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Days 8, 15, 22 and 29 ]
    Number of days of hospitalization among survivors (Phase 3 Cohort 1: Critical ITT population)

  51. Number of Participants With Any Serious Adverse Event [ Time Frame: Up to day 60 ]
  52. Number of Participants With Grade 4 Neutropenia (ANC <500/mm3) [ Time Frame: Up to day 60 ]
    Grade 4 Neutropenia defined as Absolute Neutrophil Count (ANC) of less than 500 per cubic millimeter(mm3)

  53. Number of Participants With Severe or Life-threatening Bacterial, Invasive Fungal, or Opportunistic Infection [ Time Frame: Up to day 60 ]
  54. Number of Participants With Grade 4 Neutropenia and Concurrent Invasive Infection [ Time Frame: Up to day 60 ]
  55. Number of Participants With Grade >=2 Infusion Related Reactions [ Time Frame: Up to day 60 ]
  56. Number of Participants With Grade >=2 Hypersensitivity Reactions [ Time Frame: Up to day 60 ]
  57. Number of Participants With Gastrointestinal Perforation [ Time Frame: Up to day 60 ]
  58. Mean Observed Leukocyte Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  59. Mean Observed Leukocyte Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  60. Mean Observed Hemoglobin Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  61. Mean Observed Hemoglobin Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  62. Mean Observed Platelet Count Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  63. Mean Observed Platelet Count Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  64. Mean Observed Total Bilirubin Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  65. Mean Observed Total Bilirubin Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  66. Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  67. Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  68. Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  69. Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  70. Mean Observed Creatinine Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  71. Mean Observed Creatinine Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04315298


Locations
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Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] June 11, 2020
Statistical Analysis Plan  [PDF] April 13, 2020
Informed Consent Form  [PDF] June 24, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04315298    
Other Study ID Numbers: 6R88-COV-2040
First Posted: March 19, 2020    Key Record Dates
Results First Posted: September 23, 2021
Last Update Posted: September 23, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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
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).
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
COVID-19
SARS-COV-2
coronavirus
IL-6
sarilumab
acute respiratory distress syndrome
treatment
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases