Study of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

COVID-19 Clinical Trial

— COMMUNITY  

Official title:

Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04590586
• Other study ID #: COV-01
• Status: Completed
• Phase: Phase 3
• Start date: November 24, 2020
• Est. completion date: August 3, 2021

Study information

• Verified date: June 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 515
• Est. completion date: August 3, 2021
• Est. primary completion date: August 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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] a 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).

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Standard 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.
• Apremilast
Apremilast administered orally as a tablet.
• Apremilast placebo
Matching apremilast placebo administered orally as a tablet.
• Lanadelumab
Lanadelumab administered as an intravenous (IV) infusion.
• Lanadelumab placebo
Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.
• Zilucoplan
Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
• Zilucoplan placebo
Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano	Ciudad Autonoma Buenos Aires
Argentina	Hospital General de Agudos Dr. Ignacio Pirovano	Ciudad Autonoma Buenos Aires
Argentina	Hospital General de Agudos Dr. J. M. Ramos Mejia	Ciudad Autonoma Buenos Aires
Argentina	Hospital San Juan de Dios	Ramos Mejia	Buenos Aires
Argentina	Hospital Italiano de Rosario	Rosario
Brazil	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu	Botucatu	Sao Paulo
Brazil	Chronos Pesquisa Clinica	Brasília	Distrito Federal
Brazil	HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás	Goiânia	Goiás
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Praxis Pesquisa Médica	Santo André	Sao Paulo
Chile	Hospital Base Osorno	Osorno
Mexico	Hospital Civil de Culiacan	Culiacán	Sinaloa
Mexico	Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	Jalisco
Mexico	Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo León
Mexico	Hospital General de Tijuana	Tijuana	Baja California Norte
Russian Federation	TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich	Krasnoyarsk
Russian Federation	SBIH of Moscow "Infectious Clinical Hospital # 1 of Department of Healthcare of Moscow"	Moscow
Russian Federation	SPb SBIH "Alexandrovskaya City Hospital"	Saint Petersburg
Russian Federation	SPb SBIH "City Pokrovskaya Hospital"	Saint Petersburg
Russian Federation	SPb SBIH "Nikolaevskaya Hospital"	Saint Petersburg
Russian Federation	St-George Hospital	Saint Petersburg
Russian Federation	SPb SBIH "City Hospital # 40 of Kurortnyi region"	Sestroretsk
South Africa	2 Military Hospital Internal Medicine	Cape Town	Western Cape
South Africa	Tiervlei Trial Centre	Cape Town	Western Cape
South Africa	Tread Research	Cape Town	Western Cape
South Africa	Johese Clinical Research: Unitas	Centurion	Gauteng
South Africa	Drs Sarvan and Moodley	Durban	KwaZulu-Natal
South Africa	MERC SiReN	Johannesburg	Gauteng
South Africa	Nelson Mandela Academic Clinical Research Unit (NeMACRU)	Mthatha	Eastern Cape
South Africa	Dr JM Engelbrecht Trial Site	Somerset West	Western Cape
South Africa	Clinical Projects Research SA (PTY) LTD	Worcester	Western Cape
Ukraine	Communal Noncommercial Profit "Clinical City Hospital 16 of Dnipro Regional Council"	Dnipro
Ukraine	CNE of Kharkov RC Reg Cl Infectious Hospital	Kharkiv
Ukraine	Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1"	Kremenchuk
Ukraine	City Clinical infectious Hospital	Odesa
Ukraine	Municipal Non-Profit Enterprise Central City Hospital Of Rivne City Council	Rivne
Ukraine	CCH #1 Vinnytsia M.I.Pyrogov NMU Ch of Infectious Diseases	Vinnytsia
United States	Pinnacle Research Group LLC	Anniston	Alabama
United States	Grady Health System	Atlanta	Georgia
United States	Good Samaritan Hospital	Bakersfield	California
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Sharp Chula Vista Medical Center	Chula Vista	California
United States	Harper University Hospital	Detroit	Michigan
United States	Sinai Grace Hospital	Detroit	Michigan
United States	El Centro Regional Medical Center	El Centro	California
United States	Medical City Ft. Worth	Fort Worth	Texas
United States	UF Health Shands Hospital	Gainesville	Florida
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	The University of Iowa	Iowa City	Iowa
United States	Memorial Hospital Jacksonville	Jacksonville	Florida
United States	University of Tennessee Health Sciences Center	Memphis	Tennessee
United States	University of California Irvine Medical Center	Orange	California
United States	Riverside Community Hospital	Riverside	California
United States	Detroit Receiving Hospital	Royal Oak	Michigan
United States	National Institute of Clinical Research	S. El Monte	California
United States	University of California Davis Health System	Sacramento	California
United States	Texoma Medical Center	Sherman	Texas
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Mexico,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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
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.	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
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.	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
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.	Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Baseline (Day 1) and Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; 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.	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 2 to Day 29
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).	Day 1 to Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 60
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.	From first dose of study drug to end of study (Day 60)
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.	Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Baseline (Day 1) and Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; 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.	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 2 to Day 29
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).	Day 1 to Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 60
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.	From first dose of study drug to end of study (Day 60)
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.	Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Baseline (Day 1) and Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; 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.	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 2 to Day 29
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).	Day 1 to Day 29
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.	Day 1 to Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high-flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 8, Day 15, and Day 29
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: Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on noninvasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care; Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities	Day 60
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.	From first dose of study drug to end of study (Day 60)