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

Phase 2

Completed

Conditions: COVID-19

Interventions: Drug: Sarilumab
Drug: Placebo

Registration Number: NCT04315298

Lead Sponsor: 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1912

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sarilumab 200mg IV (P2)	Sarilumab	Phase 2
Sarilumab 200mg IV (P3:C1)	Sarilumab	Phase 3: Cohort 1
Sarilumab 400mg IV (P3:C1)	Sarilumab	Phase 3: Cohort 1
Sarilumab 800mg IV (P3:C2)	Sarilumab	Phase 3: Cohort 2
Sarilumab 200mg IV (P2)	Placebo	Phase 2
Sarilumab 200mg IV (P3:C1)	Placebo	Phase 3: Cohort 1
Sarilumab 400mg IV (P2)	Placebo	Phase 2
Sarilumab 800mg IV (P3: C3)	Placebo	Phase 3: Cohort 3
Sarilumab 400mg IV (P3:C1)	Placebo	Phase 3: Cohort 1
Sarilumab 800mg IV (P3:C2)	Placebo	Phase 3: Cohort 2
Sarilumab 800mg IV (P3: C3)	Sarilumab	Phase 3: Cohort 3
Sarilumab 400mg IV (P2)	Sarilumab	Phase 2

Primary Outcome Measures

Name	Time	Method
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)	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)	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
Percent Change From Baseline in CRP Levels at Day 4 in Participants With Serum IL-6 Level Greater Than the ULN (Phase 2)	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.

Secondary Outcome Measures

Name	Time	Method
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)	Up to Day 22	Summary of Ventilator-free days during study in Participants using Invasive Mechanical Ventilation at Baseline
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 Deaths Due to Any Cause	Up to day 60	Number of deaths due to any cause (All-Cause Mortality)
Time to Death (Phase 3 Cohort 1: Critical ITT)	Up to day 60	Time to Death (All-Cause Mortality)
Time to Death (Phase 3 Cohort 2)	Up to day 60	Time to Death (All-Cause Mortality)
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)
Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1: Critical ITT)	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	Up to day 60
Number of Participants With Grade >=2 Hypersensitivity Reactions	Up to day 60
Mean Observed Creatinine Values Across Study Days (Phase 3)	Days 1, 4, 15 and 29
Time to Resolution of Fever and Improvement in Oxygenation for at Least 48 Hours (Phase 2)	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 Alive, Off Oxygen (Phase 2)	At Day 29
Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With All Serum IL-6 Levels (Phase 2)	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 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)	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 Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, by Baseline IL-6 Levels (Phase 2)	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 by Baseline IL-6 Levels (Phase 2)	Up to day 29	Time to Improvement defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Change From Baseline in NEWS2 Scoring System (Phase 2)	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).
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	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)	Up to Day 29 and Day 60	Percentage of Participants who die through Day 29 and Day 60
Time to Discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and Maintained for 24 Hours (Phase 2)	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).
Number of Participants Who Initiated Mechanical Ventilation After Baseline (Phase 2)	Up to Day 29
Number of Days of Hospitalization Among Survivors (Phase 2)	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)	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)	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 Improvement in Oxygenation for at Least 48 Hours (Phase 2)	Up to day 29	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)	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
Number of Days With Fever (Phase 2)	Up to Day 29	Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)
Number of Days of Resting Respiratory Rate >24 Breaths/Min (Phase 2)	Up to day 29
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)	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 Die (Phase 3 Cohort 1: Critical ITT)	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)	At Day 22	Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)	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)	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 Recovery (Phase 3 Cohort 2)	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)	Up to day 60	Phase 3 Cohort 1 Time to Death (All-Cause Mortality)
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical ITT)	Days 8, 15, 22 and 29	Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)
Number of Participants With Grade 4 Neutropenia (ANC <500/mm3)	Up to day 60	Grade 4 Neutropenia defined as Absolute Neutrophil Count (ANC) of less than 500 per cubic millimeter(mm3)
Mean Observed Leukocyte 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 Total Bilirubin Across Study Days (Phase 3)	Days 1, 4, 15 and 29
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical ITT)	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 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)	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)	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)	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)	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)	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)	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)	Day 22
Percentage of Patients Discharged and Alive (Phase 3 Cohort 1)	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)	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)	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)	Up to day 29	Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)	Days 8, 15, 22 and 29	Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)
Number of Participants With Grade 4 Neutropenia and Concurrent Invasive Infection	Up to day 60
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
Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT)	Day 22
Number of Participants With Severe or Life-threatening Bacterial, Invasive Fungal, or Opportunistic Infection	Up to day 60
Number of Participants With Grade >=2 Infusion Related Reactions	Up to day 60
Number of Participants With Gastrointestinal Perforation	Up to day 60
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 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 Total Bilirubin Values Across Study Days (Phase 2)	Days 1, 4, 15 and 29
Mean Observed Aspartate 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

Trial Locations

Locations (3): Regeneron Study Site
🇺🇸
Renton, Washington, United States
Regeneron Study Site 1
🇺🇸
New York, New York, United States
Regeneron Study Site 2
🇺🇸
New York, New York, United States