The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.
This adaptive, randomized, placebo-controlled platform study is designed to rapidly assess multiple candidate agents as treatments for COVID-19 in hospitalized patients. Candidate agents will be evaluated frequently (through ongoing monitoring) for futility and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation. For inclusion, participants will need to be hospitalized with a clinical status of Grade 2 to Grade 5, as defined by the following Clinical Severity Status 8-Point Ordinal Scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities Participants will be randomized equally to either the candidate agent plus standard of care (SoC) or placebo plus SoC in a double-blind fashion. Participants who are randomized to placebo plus SoC will subsequently be randomized equally to a matching placebo corresponding to an available agent whose sub-protocol the patient qualified for (ie, a 2-stage randomization). Each participant in the placebo plus SoC group will only receive one type of placebo. Randomization will be stratified by baseline clinical severity of 2 on the 8-point ordinal scale (yes/no) and remdesivir use at baseline (yes/no). The study will evaluate each candidate agent separately as an add-on to the SoC to assess safety and efficacy. The comparator group for a candidate agent will include participants randomized to the placebo arm of any sub-protocol according to the following conditions: * Apremilast sub-protocol: participants who were enrolled concurrently to apremilast and who would have been eligible for the apremilast sub-protocol. * Lanadelumab sub-protocol: at a site where at least one participant was randomized to either lanadelumab active or placebo arms. * Zilucoplan sub-protocol: at a site where at least one participant was randomized to either the zilucoplan active or placebo arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
515
Standard of care (SoC) treatment for COVID-19 infection in line with institutional practice. The SoC may change as new information becomes available about treating COVID-19.
Apremilast administered orally as a tablet.
Matching apremilast placebo administered orally as a tablet.
Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.
Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.
Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
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Lanadelumab administered as an intravenous (IV) infusion.
Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.
Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
Pinnacle Research Group LLC
Anniston, Alabama, United States
Good Samaritan Hospital
Bakersfield, California, United States
Sharp Chula Vista Medical Center
Chula Vista, California, United States
El Centro Regional Medical Center
El Centro, California, United States
University of California Irvine Medical Center
Orange, California, United States
Riverside Community Hospital
Riverside, California, United States
University of California Davis Health System
Sacramento, California, United States
National Institute of Clinical Research
South El Monte, California, United States
UF Health Shands Hospital
Gainesville, Florida, United States
Memorial Hospital Jacksonville
Jacksonville, Florida, United States
...and 49 more locations
Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.
Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.
Time frame: Day 29
Lanadelumab Sub-protocol: Percentage of Participants With a ≥ 2-point Improvement From Baseline or Fit for Discharge on the Clinical Severity Status 8-Point Ordinal Scale at Day 29
Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29. The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Baseline (Day 1) and Day 29
Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.
Time frame: Day 1 to Day 29
Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29
The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.
Time frame: Day 8, Day 15, and Day 29
Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29
The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint. The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 2 to Day 29
Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29
Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).
Time frame: Day 1 to Day 29
Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29
Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.
Time frame: Day 1 to Day 29
Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29
Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 8, Day 15, and Day 29
Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery
Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 60
Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A Serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above. The Investigator assessed the intensity of each AE according to the Common Terminology Criteria for Adverse Events (CTCAE): * Grade 1 Mild; asymptomatic or mild symptoms; * Grade 2 Moderate; minimal, local or noninvasive intervention indicated; * Grade 3 Severe or medically significant, not immediately life-threatening; * Grade 4 Life-threatening; urgent intervention indicated; * Grade 5 Death due to AE.
Time frame: From first dose of study drug to end of study (Day 60)
Apremilast Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.
Time frame: Day 29
Apremilast Sub-protocol: Percentage of Participants With a ≥ 2-point Improvement From Baseline or Fit for Discharge on the Clinical Severity Status 8-Point Ordinal Scale at Day 29
Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29. The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Baseline (Day 1) and Day 29
Apremilast Sub-protocol: Percentage of Participants Who Died Before or on Day 29
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.
Time frame: Day 1 to Day 29
Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29
The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.
Time frame: Day 8, Day 15, and Day 29
Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29
The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint. The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 2 to Day 29
Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29
Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).
Time frame: Day 1 to Day 29
Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29
Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.
Time frame: Day 1 to Day 29
Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29
Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 8, Day 15, and Day 29
Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery
Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 60
Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above. The Investigator assessed the intensity of each AE according to the CTCAE grades: * Grade 1 Mild; asymptomatic or mild symptoms; * Grade 2 Moderate; minimal, local or noninvasive intervention indicated; * Grade 3 Severe or medically significant, not immediately life-threatening; * Grade 4 Life-threatening; urgent intervention indicated; * Grade 5 Death due to AE.
Time frame: From first dose of study drug to end of study (Day 60)
Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.
Time frame: Day 29
Zilucoplan Sub-protocol: Percentage of Participants With a ≥ 2-point Improvement From Baseline or Fit for Discharge on the Clinical Severity Status 8-Point Ordinal Scale at Day 29
Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29. The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Baseline (Day 1) and Day 29
Zilucoplan Sub-protocol: Percentage of Participants Who Died Before or on Day 29
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.
Time frame: Day 1 to Day 29
Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29
The clinical severity status 8-point ordinal scale scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.
Time frame: Day 8, Day 15, and Day 29
Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29
The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale scores, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care were considered as having a score of 1 (death) instead of a score of 7 for this endpoint. The clinical severity status 8-point ordinal scale scores scores are: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive 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, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 2 to Day 29
Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29
Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).
Time frame: Day 1 to Day 29
Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29
Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.
Time frame: Day 1 to Day 29
Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29
Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 8, Day 15, and Day 29
Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery
Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery. Clinical severity status 8-point ordinal scale: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on noninvasive ventilation or high flow oxygen devices 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care 7. Not hospitalized, limitation on activities and/or requiring home oxygen 8. Not hospitalized, no limitations on activities
Time frame: Day 60
Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events
An adverse event is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above. The Investigator assessed the intensity of each AE according to the CTCAE grades: * Grade 1 Mild; asymptomatic or mild symptoms; * Grade 2 Moderate; minimal, local or noninvasive intervention indicated; * Grade 3 Severe or medically significant, not immediately life-threatening; * Grade 4 Life-threatening; urgent intervention indicated; * Grade 5 Death due to AE.
Time frame: From first dose of study drug to end of study (Day 60)