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Trial record 3 of 17 for:    kevzara covid

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 15, 2020
First Posted Date  ICMJE March 19, 2020
Results First Submitted Date  ICMJE July 23, 2021
Results First Posted Date  ICMJE September 23, 2021
Last Update Posted Date September 23, 2021
Actual Study Start Date  ICMJE March 18, 2020
Actual Primary Completion Date July 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 23, 2021)
  • 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.
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Time to resolution of fever for at least 48 hours without antipyretics for 48 hours [ Time Frame: Up to day 29 ]
    Phase 2 Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)
  • Percentage of patients reporting each severity rating on a 6-point ordinal scale [ Time Frame: Day 15 ]
    Phase 3 6-point Ordinal Scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2021)
  • 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
  • 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
  • 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).
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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).
  • 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).
  • 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)
  • Percentage of Participants Alive, Off Oxygen (Phase 2) [ Time Frame: At Day 29 ]
  • Number of Days of Resting Respiratory Rate >24 Breaths/Min (Phase 2) [ Time Frame: Up to day 29 ]
  • Number of Days With Hypoxemia (Phase 2) [ Time Frame: Up to day 29 ]
  • Number of Days of Supplemental Oxygen Use (Phase 2) [ Time Frame: Up to day 29 ]
  • Time to Saturation ≥94% on Room Air (Phase 2) [ Time Frame: Up to day 29 ]
  • 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
  • Number of Participants Who Initiated Mechanical Ventilation After Baseline (Phase 2) [ Time Frame: Up to Day 29 ]
  • 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 ]
  • Number of Days of Hospitalization Among Survivors (Phase 2) [ Time Frame: Up to day 29 ]
  • Number of Deaths Due to Any Cause [ Time Frame: Up to day 60 ]
    Number of deaths due to any cause (All-Cause Mortality)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 ]
  • Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Day 22 ]
  • Percentage of Patients Discharged and Alive (Phase 3 Cohort 1) [ Time Frame: At Day 22 ]
    Percentage of Patients Discharged and Alive at Day 22
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • Time to Death (Phase 3 Cohort 1: Critical ITT) [ Time Frame: Up to day 60 ]
    Time to Death (All-Cause Mortality)
  • Time to Death (Phase 3 Cohort 2) [ Time Frame: Up to day 60 ]
    Time to Death (All-Cause Mortality)
  • 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)
  • 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)
  • 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)
  • 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)
  • Number of Participants With Any Serious Adverse Event [ Time Frame: Up to day 60 ]
  • 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)
  • Number of Participants With Severe or Life-threatening Bacterial, Invasive Fungal, or Opportunistic Infection [ Time Frame: Up to day 60 ]
  • Number of Participants With Grade 4 Neutropenia and Concurrent Invasive Infection [ Time Frame: Up to day 60 ]
  • Number of Participants With Grade >=2 Infusion Related Reactions [ Time Frame: Up to day 60 ]
  • Number of Participants With Grade >=2 Hypersensitivity Reactions [ Time Frame: Up to day 60 ]
  • Number of Participants With Gastrointestinal Perforation [ Time Frame: Up to day 60 ]
  • Mean Observed Leukocyte Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Leukocyte Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Hemoglobin Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Hemoglobin Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Platelet Count Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Platelet Count Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Total Bilirubin Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Total Bilirubin Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Aspartate Aminotransferase Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Alanine Aminotransferase Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Creatinine Values Across Study Days (Phase 2) [ Time Frame: Days 1, 4, 15 and 29 ]
  • Mean Observed Creatinine Values Across Study Days (Phase 3) [ Time Frame: Days 1, 4, 15 and 29 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2020)
  • Time to improvement in oxygenation for at least 48 hours [ Time Frame: Up to day 29 ]
    Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
  • Mean change in the 6-point ordinal scale [ Time Frame: Up to day 29 ]
    6-point Ordinal Scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized
  • Clinical status using the 6-point ordinal scale [ Time Frame: Up to day 29 ]
    6-point Ordinal Scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized
  • Time to improvement in one category from admission using the 6-point ordinal scale [ Time Frame: Up to day 29 ]
    6-point Ordinal Scale:
    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO;
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen
    6. Not hospitalized
  • Time to resolution of fever for at least 48 hours without antipyretics by clinical severity [ Time Frame: Up to day 29 ]
    Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)
  • Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels [ Time Frame: Up to day 29 ]
    Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic)
  • Time to improvement in oxygenation for at least 48 hours by clinical severity [ Time Frame: Up to day 29 ]
    Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
  • Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels [ Time Frame: Up to day 29 ]
    Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
  • Time to resolution of fever and improvement in oxygenation for at least 48 hours [ Time Frame: Up to day 29 ]
    Resolution of fever defined as Defined as ≤36.6°C (axilla), ≤37.2°C (oral) or ≤37.8°C (rectal or tympanic). Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
  • Time to change in National Early Warning Score 2 (NEWS2) scoring system [ Time Frame: Up to day 29 ]
    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
  • Time to score of <2 maintained for 24 hours in NEWS2 scoring system [ Time Frame: Up to day 29 ]
    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
  • Mean change in NEWS2 scoring system [ Time Frame: Up to day 29 ]
    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
  • Number of days with fever [ Time Frame: Up to day 29 ]
    Defined as >36.6°C (axilla), >37.2°C (oral) or >37.8°C (rectal or tympanic)
  • Number of patients alive off oxygen [ Time Frame: Day 29 ]
  • Number of days of resting respiratory rate >24 breaths/min [ Time Frame: Up to day 29 ]
  • Number of days with hypoxemia [ Time Frame: Up to day 29 ]
  • Number of days of supplemental oxygen use [ Time Frame: Up to day 29 ]
  • Time to saturation ≥94% on room air [ Time Frame: Up to day 29 ]
  • Number of ventilator free days in the first 28 days [ Time Frame: Baseline to day 29 ]
  • Number of patients requiring initiation of mechanical ventilation [ Time Frame: Up to day 29 ]
  • Number of patients requiring non-invasive ventilation [ Time Frame: Up to day 29 ]
  • Number of patients requiring the use of high flow nasal cannula [ Time Frame: Up to day 29 ]
  • Number of patients admitted into an intensive care unit (ICU) [ Time Frame: Up to day 29 ]
  • Number of days of hospitalization among survivors [ Time Frame: Up to day 29 ]
  • Number of deaths due to any cause [ Time Frame: Up to day 60 ]
  • Incidence of serious adverse events [ Time Frame: Up to day 60 ]
  • Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection [ Time Frame: Up to day 29 ]
  • Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with grade 4 neutropenia [ Time Frame: Up to day 60 ]
  • Incidence of hypersensitivity reactions [ Time Frame: Up to day 29 ]
  • Incidence of infusion reactions [ Time Frame: Up to day 29 ]
  • Incidence of gastrointestinal perforation [ Time Frame: Up to day 60 ]
  • White blood cell count [ Time Frame: Up to day 29 if still hospitalized ]
  • Hemoglobin levels [ Time Frame: Up to day 29 if still hospitalized ]
  • Platelet count [ Time Frame: Up to day 29 if still hospitalized ]
  • Creatinine levels [ Time Frame: Up to day 29 if still hospitalized ]
  • Total bilirubin level [ Time Frame: Up to day 29 if still hospitalized ]
  • Alanine aminotransferase level [ Time Frame: Up to day 29 if still hospitalized ]
  • Aspartate aminotransferase level [ Time Frame: Up to day 29 if still hospitalized ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19
Official Title  ICMJE An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Sarilumab 200mg IV (P2)
    Phase 2
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
  • Experimental: Sarilumab 200mg IV (P3:C1)
    Phase 3: Cohort 1
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
  • Experimental: Sarilumab 400mg IV (P2)
    Phase 2
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
  • Experimental: Sarilumab 400mg IV (P3:C1)
    Phase 3: Cohort 1
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
  • Experimental: Sarilumab 800mg IV (P3:C2)
    Phase 3: Cohort 2
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
  • Experimental: Sarilumab 800mg IV (P3: C3)
    Phase 3: Cohort 3
    Interventions:
    • Drug: Sarilumab
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 16, 2020)
1912
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2020)
400
Actual Study Completion Date  ICMJE September 2, 2020
Actual Primary Completion Date July 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04315298
Other Study ID Numbers  ICMJE 6R88-COV-2040
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All IPD that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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/
Current Responsible Party Regeneron Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Regeneron Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP