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)
description: 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_frame: Up to Day 29
Time to Improvement (2 Points) in Clinical Status Assessment in Severe or Critical Patients With All Serum IL-6 Levels (Phase 2)
description: 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_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 at Baseline (Phase 2)
description: 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_frame: Up to Day 29
Time to Resolution of Fever for at Least 48 Hours Without Antipyretics by Clinical Severity (Phase 2)
description: 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_frame: Up to day 29
Time to Resolution of Fever for at Least 48 Hours Without Antipyretics or Until Discharge, Whichever is Sooner, by Baseline IL-6 Levels (Phase 2)
description: 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_frame: Up to Day 29
Time to Improvement in Oxygenation for at Least 48 Hours (Phase 2)
description: Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
time_frame: Up to day 29
Time to Improvement in Oxygenation for at Least 48 Hours by Baseline IL-6 Levels (Phase 2)
description: Time to Improvement defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
time_frame: Up to day 29
Time to Resolution of Fever and Improvement in Oxygenation for at Least 48 Hours (Phase 2)
description: 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
time_frame: Up to day 29
Percentage of Participants in Each Clinical Status Category Using the 7-point Ordinal Scale up to Day 29 (Phase 2)
description: 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_frame: Days 1, 3, 5, 8, 11, 15 and 29
Time to Discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and Maintained for 24 Hours (Phase 2)
description: 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).
time_frame: Up to day 29
Change From Baseline in NEWS2 Scoring System (Phase 2)
description: 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).
time_frame: Days 3, 5, 8, 11, 15 and 29
Number of Days With Fever (Phase 2)
description: Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)
time_frame: Up to Day 29
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)
description: Summary of Ventilator-free days during study in Participants using Invasive Mechanical Ventilation at Baseline
time_frame: Up to Day 22
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
description: Number of deaths due to any cause (All-Cause Mortality)
time_frame: Up to day 60
Percentage of Participants With at Least 1-point Improvement in Clinical Status Using the 7-point Ordinal Scale in Participants With Critical COVID-19 (Phase 3 Cohort 1: Critical ITT)
description: 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_frame: Day 22
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22
time_frame: Day 22
Percentage of Participants Who Recover (Phase 3 Cohort 1: Critical ITT)
description: Percentage of Participants Who Recover (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use) at Day 22
time_frame: Day 22
Percentage of Participants Who Die (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Percentage of Participants who die through Day 29 and Day 60
time_frame: Up to Day 29 and Day 60
Percentage of Participants Who Die (Phase 3 Cohort 1: Critical ITT)
description: Percentage of Participants who die through Day 29 and Day 60
time_frame: Up to Day 29 and Day 60
Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)
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 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: 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_frame: At Day 22
Percentage of Participants Alive Not Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical ITT)
description: Percentage of participants alive not receiving mechanical ventilation or ECMO at Day 22 (Phase 3 Cohort 1)
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 (Phase 3 Cohort 1: Critical ITT)
description: 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_frame: At Day 22
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: 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_frame: Up to day 29
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)
description: 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_frame: Up to day 29
Time to at Least 1-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 2)
description: 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_frame: Up to day 29
Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1)
description: 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_frame: Up to day 29
Time to at Least 2-point Improvement in Clinical Status Assessment on the 7-point Ordinal Scale (Phase 3 Cohort 1: Critical ITT)
description: 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_frame: Up to day 29
Percentage of Participants Receiving Mechanical Ventilation or ECMO at Day 22 (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
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)
description: Percentage of Patients Discharged and Alive at Day 22
time_frame: At Day 22
Percentage of Participants Discharged and Alive at Day 22 (Phase 3 Cohort 1: Critical ITT)
description: Percentage of Participants Discharged and Alive at Day 22
time_frame: At Day 22
Time to Recovery (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)
time_frame: Up to day 29
Time to Recovery (Phase 3 Cohort 1: Critical ITT)
description: Phase 3 Cohort 1 Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)
time_frame: Up to day 29
Time to Recovery (Phase 3 Cohort 2)
description: Time to Recovery (Discharged, or Alive without Supplemental Oxygen Use or at Pre-COVID Oxygen Use)
time_frame: Up to day 29
Time to Death (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Phase 3 Cohort 1 Time to Death (All-Cause Mortality)
time_frame: Up to day 60
Time to Death (Phase 3 Cohort 1: Critical ITT)
description: Time to Death (All-Cause Mortality)
time_frame: Up to day 60
Time to Death (Phase 3 Cohort 2)
description: Time to Death (All-Cause Mortality)
time_frame: Up to day 60
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical on Mechanical Ventilation at Baseline)
description: Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)
time_frame: Days 8, 15, 22 and 29
Number of Ventilator-Free Days (Phase 3 Cohort 1: Critical ITT)
description: Number of Ventilator-Free days up to Day 29 (Phase 3 Cohort 1)
time_frame: Days 8, 15, 22 and 29
Number of Days of Hospitalization Among Survivors (Phase 3 Cohort 1)
description: 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: Critical ITT)
description: Number of days of hospitalization among survivors (Phase 3 Cohort 1: Critical ITT population)
time_frame: Days 8, 15, 22 and 29
Number of Participants With Any Serious Adverse Event
time_frame: Up to day 60
Number of Participants With Grade 4 Neutropenia (ANC <500/mm3)
description: Grade 4 Neutropenia defined as Absolute Neutrophil Count (ANC) of less than 500 per cubic millimeter(mm3)
time_frame: Up to day 60
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 [2]