COVID-19
Conditions
Keywords
SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2
Brief summary
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.
Detailed description
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.
Interventions
DRUGStandard of care
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.
DRUGApremilast
Apremilast administered orally as a tablet.
DRUGApremilast placebo
Matching apremilast placebo administered orally as a tablet.
DRUGLanadelumab
Lanadelumab administered as an intravenous (IV) infusion.
DRUGLanadelumab placebo
Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.
DRUGZilucoplan
Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
DRUGZilucoplan placebo
Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥18 years of age) with active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by laboratory tests and/or point of care tests (eg, commercial or public health assay, which is approved for emergency use). If no diagnostic test results are available that have been obtained during the previous 72 hours, then a test should be performed as part of the screening assessment. * A score of Grade 2 (hospitalized, on invasive mechanical ventilation or ECMO), Grade 3 (hospitalized, on noninvasive ventilation or high-flow oxygen devices), Grade 4 (hospitalized, requiring supplemental oxygen), or Grade 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care \[COVID-19 related or otherwise\]), as defined by an 8 point ordinal scale. * Male participants: * A male participant must agree to use contraception during the treatment period and for at least 6 weeks after the last dose of study treatment and refrain from donating sperm during this period. * Female participants: * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: * Not a woman of childbearing potential (WOCBP). OR * A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 weeks after the last dose of study treatment. * Ability to provide informed consent signed by the study participant or legally authorized representative. * Ability and willingness to participate in telephone/telemedicine follow-up visits if needed. * Zilucoplan only: Antibiotic prophylaxis: all participants must be willing to take antibiotic prophylaxis concomitantly, starting with the first dose of zilucoplan or placebo.
Exclusion criteria
* Participant has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments (eg, participants unable to swallow study medication tablets). * Stage 4 severe chronic kidney disease or requiring dialysis. * Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia correction (QTcF) ≥ 500 ms. * Anticipated transfer to another hospital that is not a study center within 72 hours. * Participants who are currently pregnant or who are not willing to discontinue breastfeeding. * Participants participating in another clinical study of an investigational medicinal product or other unapproved (or investigational) treatment for COVID-19. * Active tuberculosis or a history of incompletely treated tuberculosis. * Active, uncontrolled systemic bacterial or fungal infection(s). * Apremilast only: Current treatment with apremilast, or another agent of similar mechanism of action, for any indication within 1 week prior to first dose of investigational product. * Apremilast only: Concurrent use at screening or randomization of cytochrome P450 (CYP)3A inducers (eg, rifampin, phenobarbital, carbamazepine) within 1 week prior to first dose of investigational product. * Apremilast only: Known hypersensitivity to apremilast or any excipients in formulation. * Lanadelumab only: Known or suspected hypersensitivity to lanadelumab or any of its excipients. * Lanadelumab only: Previous (within 3 months prior to baseline) or current use of immunomodulators (eg, methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis factor \[TNF\] α inhibitor, Janus kinase \[JAK\] inhibitor, alpha-integrin inhibitor). * Lanadelumab only: Known or suspected venous thromboembolism. * Lanadelumab only: Previous (within 3 months \[or 5 half-lives, whichever is greater\] of screening) or current use of plasma kallikrein (pKal) inhibitor or bradykinin receptor blocker. * Zilucoplan only: Participants with unresolved or suspected infection with Neisseria meningitidis or a past history of N. meningitidis (eg, in a complement-deficient patient).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 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 | 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. |
| Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 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 | 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. |
| Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8, Day 15, and 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 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. |
| Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | Day 2 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 |
| Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | Day 1 to 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). |
| Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | Day 1 to 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. |
| Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8, Day 15, and Day 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 |
| Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | Day 60 | 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 |
| Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug to end of study (Day 60) | 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. |
| Apremilast Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 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. |
| 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 | Baseline (Day 1) and 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 |
| Apremilast Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | Day 1 to 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. |
| Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8, Day 15, and 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 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. |
| Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Day 2 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 |
| Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | Day 1 to 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). |
| Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 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. |
| Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 8, Day 15, and Day 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 |
| Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | Day 60 | 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 |
| Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug to end of study (Day 60) | 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. |
| Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 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. |
| 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 | Baseline (Day 1) and 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 |
| Zilucoplan Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | Day 1 to 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. |
| Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8, Day 15, and 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 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. |
| Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Day 2 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 |
| Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | Day 1 to 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). |
| Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | Day 1 to 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. |
| Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8, Day 15, and Day 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 |
| Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | Day 60 | 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 |
| Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | From first dose of study drug to end of study (Day 60) | 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. |
| Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | Day 1 to 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. |
| 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 | Baseline (Day 1) and 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 |
| Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | Day 1 to 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. |
Countries
Argentina, Brazil, Chile, Mexico, Russia, South Africa, Ukraine, United States
Participant flow
Recruitment details
This adaptive platform study consisted of 3 sub-protocols, each designed to assess a candidate agent as treatment for coronavirus disease 2019 (COVID-19) in hospitalized adult patients who had severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. The control group for a candidate agent includes participants randomized to any matching placebo for a candidate agent if certain criteria were met (shared placebo).
Pre-assignment details
Participants were initially randomized to an active candidate agent or generically to placebo plus standard of care (SoC) for sub-protocols for which they met eligibility. Participants randomized to placebo plus SoC were subsequently randomized equally to a matching placebo for an available candidate agent whose sub-protocol the participant qualified for. Randomization was stratified by baseline clinical severity of 2 on the 8-point ordinal scale (yes/no) and remdesivir use at baseline (yes/no).
Participants by arm
| Arm | Count |
|---|---|
| Lanadelumab + Standard of Care Participants randomized to receive lanadelumab 300 mg by intravenous infusion on Day 1, and a second dose administered on Day 4, in addition to standard of care. | 28 |
| Lanadelumab Placebo Control Includes participants randomized to receive matching placebo to lanadelumab plus standard of care treatment as well as participants who were randomized to receive placebo to apremilast or placebo to zilucoplan plus standard of care treatment at a site that enrolled at least one participant in the lanadelumab sub-protocol. | 34 |
| Apremilast + Standard of Care Participants randomized to receive 30 mg apremilast orally twice a day (BID) in addition to standard of care treatment for 14 days or until hospital discharge, whichever occurred first. | 194 |
| Apremilast Placebo Control Includes participants randomized to receive matching placebo to apremilast plus standard of care treatment as well as participants who were randomized to receive placebo to lanadelumab or placebo to zilucoplan plus standard of care treatment at a site concurrently enrolling apremilast sub-protocol participants and who would have been eligible for the apremilast sub-protocol. | 190 |
| Zilucoplan + Standard of Care Participants randomized to receive 32.4 mg zilucoplan by subcutaneous injection every day for 14 days, or until discharge if discharge was before 14 days of treatment, in addition to standard of care. | 100 |
| Zilucoplan Placebo +Control Includes participants randomized to receive matching placebo to zilucoplan plus standard of care treatment as well as participants who were randomized to receive placebo to lanadelumab or placebo to apremilast plus standard of care treatment at a site that enrolled at least one participant in the zilucoplan sub-protocol. | 75 |
| Total | 621 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 7 | 1 | 37 | 34 | 19 | 3 |
| Overall Study | Lost to Follow-up | 3 | 0 | 11 | 11 | 6 | 0 |
| Overall Study | Other | 3 | 0 | 1 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 6 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Apremilast + Standard of Care | Apremilast Placebo Control | Total | Lanadelumab + Standard of Care | Lanadelumab Placebo Control | Zilucoplan + Standard of Care | Zilucoplan Placebo +Control |
|---|---|---|---|---|---|---|---|
| Age, Continuous Apremilast Sub-protocol | 57.2 years STANDARD_DEVIATION 13.84 | 55.7 years STANDARD_DEVIATION 13.37 | 56.5 years STANDARD_DEVIATION 13.61 | — | — | — | — |
| Age, Continuous Lanadelumab Sub-protocol | — | — | 56.8 years STANDARD_DEVIATION 14.57 | 53.4 years STANDARD_DEVIATION 15.34 | 59.6 years STANDARD_DEVIATION 13.5 | — | — |
| Age, Continuous Zilucoplan Sub-protocol | — | — | 55.4 years STANDARD_DEVIATION 14.11 | — | — | 53.2 years STANDARD_DEVIATION 14.13 | 58.4 years STANDARD_DEVIATION 13.62 |
| Age, Customized Apremilast Sub-protocol ≥ 18 to ≤ 49 years | 51 Participants | 56 Participants | 107 Participants | — | — | — | — |
| Age, Customized Apremilast Sub-protocol ≥ 50 to ≤ 64 years | 76 Participants | 81 Participants | 157 Participants | — | — | — | — |
| Age, Customized Apremilast Sub-protocol ≥ 65 to ≤ 84 years | 64 Participants | 52 Participants | 116 Participants | — | — | — | — |
| Age, Customized Apremilast Sub-protocol ≥ 85 years | 3 Participants | 1 Participants | 4 Participants | — | — | — | — |
| Age, Customized Lanadelumab Sub-protocol ≥ 18 to ≤ 49 years | — | — | 21 Participants | 13 Participants | 8 Participants | — | — |
| Age, Customized Lanadelumab Sub-protocol ≥ 50 to ≤ 64 years | — | — | 22 Participants | 7 Participants | 15 Participants | — | — |
| Age, Customized Lanadelumab Sub-protocol ≥ 65 to ≤ 84 years | — | — | 18 Participants | 8 Participants | 10 Participants | — | — |
| Age, Customized Lanadelumab Sub-protocol ≥ 85 years | — | — | 1 Participants | 0 Participants | 1 Participants | — | — |
| Age, Customized Zilucoplan Sub-protocol ≥ 18 to ≤ 49 years | — | — | 64 Participants | — | — | 45 Participants | 19 Participants |
| Age, Customized Zilucoplan Sub-protocol ≥ 50 to ≤ 64 years | — | — | 65 Participants | — | — | 36 Participants | 29 Participants |
| Age, Customized Zilucoplan Sub-protocol ≥ 65 to ≤ 84 years | — | — | 42 Participants | — | — | 16 Participants | 26 Participants |
| Age, Customized Zilucoplan Sub-protocol ≥ 85 years | — | — | 4 Participants | — | — | 3 Participants | 1 Participants |
| Clinical Severity Score of 2 Apremilast Sub-protocol No (Grade 3-5) | 183 Participants | 181 Participants | 364 Participants | — | — | — | — |
| Clinical Severity Score of 2 Apremilast Sub-protocol Yes (Grade 2) | 11 Participants | 9 Participants | 20 Participants | — | — | — | — |
| Clinical Severity Score of 2 Lanadelumab Sub-protocol No (Grade 3-5) | — | — | 55 Participants | 25 Participants | 30 Participants | — | — |
| Clinical Severity Score of 2 Lanadelumab Sub-protocol Yes (Grade 2) | — | — | 7 Participants | 3 Participants | 4 Participants | — | — |
| Clinical Severity Score of 2 Zilucoplan Sub-protocol No (Grade 3-5) | — | — | 161 Participants | — | — | 92 Participants | 69 Participants |
| Clinical Severity Score of 2 Zilucoplan Sub-protocol Yes (Grade 2) | — | — | 14 Participants | — | — | 8 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Apremilast Sub-protocol Hispanic or Latino | 75 Participants | 72 Participants | 147 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Apremilast Sub-protocol Not Hispanic or Latino | 108 Participants | 112 Participants | 220 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Apremilast Sub-protocol Unknown or Not Reported | 11 Participants | 6 Participants | 17 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) Lanadelumab Sub-protocol Hispanic or Latino | — | — | 37 Participants | 18 Participants | 19 Participants | — | — |
| Ethnicity (NIH/OMB) Lanadelumab Sub-protocol Not Hispanic or Latino | — | — | 25 Participants | 10 Participants | 15 Participants | — | — |
| Ethnicity (NIH/OMB) Lanadelumab Sub-protocol Unknown or Not Reported | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Ethnicity (NIH/OMB) Zilucoplan Sub-protocol Hispanic or Latino | — | — | 97 Participants | — | — | 65 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Zilucoplan Sub-protocol Not Hispanic or Latino | — | — | 78 Participants | — | — | 35 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Zilucoplan Sub-protocol Unknown or Not Reported | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Apremilast Sub-protocol American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol Asian | 11 Participants | 7 Participants | 18 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol Black or African American | 9 Participants | 9 Participants | 18 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol More than one race | 4 Participants | 7 Participants | 11 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol Unknown or Not Reported | 19 Participants | 14 Participants | 33 Participants | — | — | — | — |
| Race (NIH/OMB) Apremilast Sub-protocol White | 151 Participants | 151 Participants | 302 Participants | — | — | — | — |
| Race (NIH/OMB) Lanadelumab Sub-protocol American Indian or Alaska Native | — | — | 5 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol Asian | — | — | 8 Participants | 0 Participants | 0 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol Black or African American | — | — | 15 Participants | 3 Participants | 2 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol More than one race | — | — | 13 Participants | 2 Participants | 1 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol Unknown or Not Reported | — | — | 15 Participants | 2 Participants | 3 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Lanadelumab Sub-protocol White | — | — | 181 Participants | 20 Participants | 28 Participants | 75 Participants | 58 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol American Indian or Alaska Native | — | — | 4 Participants | — | — | 3 Participants | 1 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol Asian | — | — | 8 Participants | — | — | 3 Participants | 5 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol Black or African American | — | — | 10 Participants | — | — | 5 Participants | 5 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol More than one race | — | — | 10 Participants | — | — | 8 Participants | 2 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol Unknown or Not Reported | — | — | 10 Participants | — | — | 6 Participants | 4 Participants |
| Race (NIH/OMB) Zilucoplan Sub-protocol White | — | — | 133 Participants | — | — | 75 Participants | 58 Participants |
| Region Apremilast Sub-protocol Eastern Europe | 51 Participants | 53 Participants | 104 Participants | — | — | — | — |
| Region Apremilast Sub-protocol Latin America | 60 Participants | 50 Participants | 110 Participants | — | — | — | — |
| Region Apremilast Sub-protocol North America | 53 Participants | 60 Participants | 113 Participants | — | — | — | — |
| Region Apremilast Sub-protocol Rest of the World | 30 Participants | 27 Participants | 57 Participants | — | — | — | — |
| Region Lanadelumab Sub-protocol Eastern Europe | — | — | 0 Participants | 0 Participants | 0 Participants | — | — |
| Region Lanadelumab Sub-protocol Latin America | — | — | 38 Participants | 18 Participants | 20 Participants | — | — |
| Region Lanadelumab Sub-protocol North America | — | — | 18 Participants | 9 Participants | 9 Participants | — | — |
| Region Lanadelumab Sub-protocol Rest of the World | — | — | 6 Participants | 1 Participants | 5 Participants | — | — |
| Region Zilucoplan Sub-protocol Eastern Europe | — | — | 20 Participants | — | — | 6 Participants | 14 Participants |
| Region Zilucoplan Sub-protocol Latin America | — | — | 98 Participants | — | — | 65 Participants | 33 Participants |
| Region Zilucoplan Sub-protocol North America | — | — | 36 Participants | — | — | 26 Participants | 10 Participants |
| Region Zilucoplan Sub-protocol Rest of the World | — | — | 21 Participants | — | — | 3 Participants | 18 Participants |
| Remdesivir Use at Baseline Apremilast Sub-protocol No | 149 Participants | 146 Participants | 295 Participants | — | — | — | — |
| Remdesivir Use at Baseline Apremilast Sub-protocol Yes | 45 Participants | 44 Participants | 89 Participants | — | — | — | — |
| Remdesivir Use at Baseline Lanadelumab Sub-protocol No | — | — | 50 Participants | 21 Participants | 29 Participants | — | — |
| Remdesivir Use at Baseline Lanadelumab Sub-protocol Yes | — | — | 12 Participants | 7 Participants | 5 Participants | — | — |
| Remdesivir Use at Baseline Zilucoplan Sub-protocol No | — | — | 144 Participants | — | — | 78 Participants | 66 Participants |
| Remdesivir Use at Baseline Zilucoplan Sub-protocol Yes | — | — | 31 Participants | — | — | 22 Participants | 9 Participants |
| Sex: Female, Male Apremilast Sub-protocol Female | 84 Participants | 72 Participants | 156 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Apremilast Sub-protocol Male | 110 Participants | 118 Participants | 228 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Lanadelumab Sub-protocol Female | 0 Participants | 0 Participants | 20 Participants | 11 Participants | 9 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Lanadelumab Sub-protocol Male | 0 Participants | 0 Participants | 42 Participants | 17 Participants | 25 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Zilucoplan Sub-protocol Female | 0 Participants | 0 Participants | 62 Participants | 0 Participants | 0 Participants | 34 Participants | 28 Participants |
| Sex: Female, Male Zilucoplan Sub-protocol Male | 0 Participants | 0 Participants | 113 Participants | 0 Participants | 0 Participants | 66 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 28 | 1 / 1 | 37 / 194 | 35 / 184 | 20 / 100 | 3 / 8 |
| other Total, other adverse events | 12 / 27 | 1 / 1 | 63 / 189 | 50 / 182 | 46 / 95 | 4 / 7 |
| serious Total, serious adverse events | 11 / 27 | 1 / 1 | 51 / 189 | 55 / 182 | 31 / 95 | 2 / 7 |
Outcome results
Primary
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
Population: The apremilast full analysis set (FAS) includes all participants who were randomized to the apremilast arm as well as all participants who were randomized to any placebo arm included in the control arm for apremilast.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 14.0 days |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 14.0 days |
p-value: 0.877995% CI: [0.77, 1.24]Stratified log-rank test
Primary
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
Population: The lanadelumab sub-protocol primary analysis set includes all participants who were randomized to lanadelumab as well as all participants who were randomized to any placebo arm included in the control arm for lanadelumab with a baseline clinical severity status of Grade 3 to Grade 5 on the clinical severity status 8-point ordinal scale.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 10.0 days |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 15.5 days |
p-value: 0.667295% CI: [0.59, 2.35]Stratified log-rank test
Primary
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
Population: The zilucoplan full analysis set includes all participants who were randomized to the zilucoplan arm as well as all participants who were randomized to any placebo arm included in the control arm for zilucoplan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 14.0 days |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29 | 15.0 days |
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 38 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 31 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 46 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 5 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 78 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 22 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 22 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 34 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 6 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 16 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 26 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 6 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 9 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 36 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 9 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 34 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 25 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 110 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 10 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 11 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 8 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 20 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 26 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 26 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 40 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 33 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 34 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 24 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 13 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 9 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 8 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 5 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 48 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 79 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 31 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 6 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 3 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 40 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 104 Participants |
Comparison: Day 8p-value: 0.911995% CI: [0.71, 1.46]Proportional odds model
Comparison: Day 15p-value: 0.647595% CI: [0.75, 1.58]Proportional odds model
Comparison: Day 29p-value: 0.907195% CI: [0.64, 1.48]Proportional odds model
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 2 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 4 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 124 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 7 days | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 9 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 10 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 12 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 14 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 17 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 18 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 20 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 23 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 25 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 27 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 28 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 29 days | 8 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 34 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 122 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 29 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 2 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 14 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 4 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 23 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 4 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 28 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 3 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 17 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 7 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 25 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 4 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 18 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 9 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 32 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 10 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 20 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 27 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 12 days | 1 Participants |
p-value: 0.974195% CI: [0.64, 1.53]Proportional odds model
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 19 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 12 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 22 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 10 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 23 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 13 days | 2 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 9 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 25 days | 3 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 26 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 11 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 29 days | 1 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 18 days | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 34 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 147 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 33 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 147 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 9 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 10 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 11 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 12 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 13 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 18 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 19 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 22 days | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 23 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 25 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 26 days | 1 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 29 days | 0 Participants |
p-value: 0.875495% CI: [0.64, 1.7]Proportional odds model
Secondary
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)
Population: Apremilast safety analysis set included all participants in the apremilast FAS who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 16 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 51 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 102 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 48 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 9 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 57 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 103 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 57 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 6 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 12 Participants |
| Lanadelumab Placebo + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 11 Participants |
| Lanadelumab Placebo + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 6 Participants |
| Lanadelumab Placebo + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 100 Participants |
| Lanadelumab Placebo + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 55 Participants |
| Lanadelumab Placebo + Standard of Care | Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 54 Participants |
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 8 | 36.6 percentage of participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 15 | 57.7 percentage of participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 29 | 66.0 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 8 | 35.8 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 15 | 60.0 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29 | Day 29 | 72.1 percentage of participants |
Comparison: Analysis of clinical recovery on Day 8p-value: 0.969595% CI: [-8.7, 9.1]Regression, Logistic
Comparison: Analysis of clinical recovery on Day 895% CI: [0.64, 1.59]
Comparison: Analysis of clinical recovery on Day 15p-value: 0.623695% CI: [-11.9, 7.1]Regression, Logistic
Comparison: Analysis of clinical recovery on Day 1595% CI: [0.59, 1.37]
Comparison: Analysis of clinical recovery on Day 29p-value: 0.166495% CI: [-14.9, 2.5]Regression, Logistic
Comparison: Analysis of clinical recovery on Day 2995% CI: [0.45, 1.15]
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 59.8 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 63.7 percentage of participants |
p-value: 0.377395% CI: [-12.9, 4.9]Regression, Logistic
95% CI: [0.52, 1.28]
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 66.0 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 66.3 percentage of participants |
p-value: 0.904395% CI: [-9.3, 8.3]Regression, Logistic
95% CI: [0.62, 1.54]
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 17.5 percentage of participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 17.4 percentage of participants |
p-value: 0.966595% CI: [-7.3, 7.6]Regression, Logistic
95% CI: [0.59, 1.74]
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | 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 | 74.7 percentage of participants |
| Lanadelumab Placebo Control | 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 | 77.9 percentage of participants |
p-value: 0.484695% CI: [-11.2, 5.3]Regression, Logistic
95% CI: [0.51, 1.37]
Secondary
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
Population: Apremilast sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 13 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 75 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 5 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 37 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 5 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 21 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Missing | 4 Participants |
| Lanadelumab + Standard of Care | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 34 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 31 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 10 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 43 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 62 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 35 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 2 Participants |
| Lanadelumab Placebo Control | Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 5 Participants |
p-value: 0.450795% CI: [0.8, 1.66]Proportional odds model
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 8 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 5 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 12 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 4 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 3 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 7 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 3 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 2 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 2 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 5 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 3 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 12 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 6 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 4 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 6 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 7 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 7 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 4 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 2 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 13 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 9 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 2 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 6 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 13 Participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 2 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 7 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 13 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 9 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 10 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 2 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 1 Participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 8 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 17 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 9 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 18 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 1 Participants |
Secondary
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)
Population: Lanadelumab safety analysis set included all participants in the lanadelumab FAS who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 2 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 11 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 17 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 11 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 1 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 18 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 22 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 18 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 3 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 5 Participants |
| Lanadelumab Placebo + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 0 Participants |
| Lanadelumab Placebo + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to dose modification | 0 Participants |
| Lanadelumab Placebo + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 1 Participants |
| Lanadelumab Placebo + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 1 Participants |
| Lanadelumab Placebo + Standard of Care | Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE with a CTCAE grade ≥ 3 | 1 Participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8 | 44.0 percentage of participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 15 | 56.0 percentage of participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 29 | 60.0 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8 | 36.7 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 15 | 56.7 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 29 | 63.3 percentage of participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 52.0 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 56.7 percentage of participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 40.0 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 56.7 percentage of participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 32.0 percentage of participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 30.0 percentage of participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | 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 | 72.0 percentage of participants |
| Lanadelumab Placebo Control | 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 | 63.3 percentage of participants |
Secondary
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
Population: Lanadelumab sub-protocol primary analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 8 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 0 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 6 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | Missing | 1 Participants |
| Lanadelumab + Standard of Care | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 8 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | Missing | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 9 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 4 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 5 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 11 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 0 Participants |
| Lanadelumab Placebo Control | Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 1 Participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 11 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 25 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 31 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 24 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 8 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 14 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 10 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 16 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 16 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 3 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 22 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 10 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 20 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 12 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 44 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 2 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 5 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 1 (Death or discharged to hospice care) | 5 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 8 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 4 (Hospitalized, requiring supplemental oxygen) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 10 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 9 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | 8 (Not hospitalized, no limitations on activities) | 12 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 8 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 1 (Death or discharged to hospice care) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 7 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 3 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 4 (Hospitalized, requiring supplemental oxygen) | 6 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | 8 (Not hospitalized, no limitations on activities) | 26 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 15 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 1 (Death or discharged to hospice care) | 18 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29 | Day 29 | 8 (Not hospitalized, no limitations on activities) | 35 Participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 7 days | 4 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 14 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 56 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 17 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 18 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 9 days | 3 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 22 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 10 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 25 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 26 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 29 days | 8 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 4 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 17 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 18 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 0 days | 34 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 1 day | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 3 days | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 4 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 5 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 6 days | 3 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 7 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 8 days | 4 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 9 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 10 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 11 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 13 days | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 14 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 15 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 17 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 18 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 21 days | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 22 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 25 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 26 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29 | 29 days | 2 Participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 22 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 12 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 9 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 25 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 13 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 26 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 7 days | 4 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 27 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 28 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 10 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 29 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 18 days | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 18 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 67 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 30 days (death or discharged to hospice care) | 18 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 0 days | 52 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 6 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 7 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 9 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 10 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 12 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 13 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 16 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 18 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 22 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 24 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 25 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 26 days | 1 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 27 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 28 days | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29 | 29 days | 0 Participants |
Secondary
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)
Population: Zilucoplan safety analysis set included all participants in the zilucoplan FAS who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to dose modification | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 31 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 65 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE with a CTCAE grade ≥ 3 | 34 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 7 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 29 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 47 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE with a CTCAE grade ≥ 3 | 29 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to dose modification | 5 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 5 Participants |
| Lanadelumab Placebo + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Lanadelumab Placebo + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE leading to dose modification | 0 Participants |
| Lanadelumab Placebo + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 4 Participants |
| Lanadelumab Placebo + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | Serious TEAE | 2 Participants |
| Lanadelumab Placebo + Standard of Care | Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events | TEAE with a CTCAE grade ≥ 3 | 3 Participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8 | 33.0 percentage of participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 15 | 53.0 percentage of participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 29 | 60.0 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 8 | 30.7 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 15 | 53.3 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29 | Day 29 | 66.7 percentage of participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 54.0 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29 | 60.0 percentage of participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 55.0 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery | 64.0 percentage of participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 18.0 percentage of participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Percentage of Participants Who Died Before or on Day 29 | 24.0 percentage of participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanadelumab + Standard of Care | 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 | 66.0 percentage of participants |
| Lanadelumab Placebo Control | 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 | 69.3 percentage of participants |
Secondary
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
Population: Zilucoplan sub-protocol full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 21 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 30 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 1 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 24 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 0 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Missing | 5 Participants |
| Lanadelumab + Standard of Care | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 14 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | Missing | 2 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 1 (Death or discharged to hospice care) | 18 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 2 (Hospitalized on invasive mechanical ventilation or ECMO) | 6 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 3 (Hospitalized on noninvasive ventilation or high-flow oxygen devices) | 12 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 4 (Hospitalized, requiring supplemental oxygen) | 29 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 5 (Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care) | 7 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 6 (Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care) | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 7 (Not hospitalized, limitation on activities and/or requiring home oxygen) | 0 Participants |
| Lanadelumab Placebo Control | Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29 | 8 (Not hospitalized, no limitations on activities) | 1 Participants |