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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Standard of care; Drug: Apremilast; Drug: Apremilast placebo; Drug: Lanadelumab; Drug: Lanadelumab placebo; Drug: Zilucoplan; Drug: Zilucoplan placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 515
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1221ADC
    • Hospital General de Agudos Dr. J. M. Ramos Mejia
  • Ciudad Autonoma Buenos Aires, Argentina, C1430EGF
    • Clinica Adventista Belgrano
  • Ciudad Autonoma Buenos Aires, Argentina, C1430BKC
    • Hospital General de Agudos Dr. Ignacio Pirovano
  • Rosario, Argentina, 2000
    • Hospital Italiano de Rosario
  • Buenos Aires
    • Ramos Mejia, Buenos Aires, Argentina, 1704
      • Hospital San Juan de Dios
• Brazil
  • Distrito Federal
    • Brasília, Distrito Federal, Brazil, 72.145-450
      • Chronos Pesquisa Clínica
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
  • Sao Paulo
    • Botucatu, Sao Paulo, Brazil, 18618-970
      • UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
    • Santo André, Sao Paulo, Brazil, 09090-790
      • Praxis Pesquisa Médica
• Chile
  • Osorno, Chile, 5290000
    • Hospital Base Osorno
• Mexico
  • Baja California Norte
    • Tijuana, Baja California Norte, Mexico, 22000
      • Hospital General de Tijuana
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Hospital Civil de Guadalajara Dr. Juan I. Menchaca
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80030
      • Hospital Civil de Culiacan
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660062
    • TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich
  • Moscow, Russian Federation, 125367
    • SBIH of Moscow "Infectious Clinical Hospital # 1 of Department of Healthcare of Moscow"
  • Saint Petersburg, Russian Federation, 193312
    • SPb SBIH "Alexandrovskaya City Hospital"
  • Saint Petersburg, Russian Federation, 194354
    • St-George Hospital
  • Saint Petersburg, Russian Federation, 198510
    • SPb SBIH "Nikolaevskaya Hospital"
  • Saint Petersburg, Russian Federation, 199106
    • SPb SBIH "City Pokrovskaya Hospital"
  • Sestroretsk, Russian Federation, 197706
    • SPb SBIH "City Hospital # 40 of Kurortnyi region"
• South Africa
  • Eastern Cape
    • Mthatha, Eastern Cape, South Africa, 5100
      • Nelson Mandela Academic Clinical Research Unit (NeMACRU)
  • Gauteng
    • Centurion, Gauteng, South Africa, 0157
      • Johese Clinical Research: Unitas
    • Johannesburg, Gauteng, South Africa, 2193
      • MERC SiReN
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4320
      • Drs Sarvan and Moodley
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • Tiervlei Trial Centre
    • Cape Town, Western Cape, South Africa, 7500
      • Tread Research
    • Cape Town, Western Cape, South Africa, 7800
      • 2 Military Hospital Internal Medicine
    • Somerset West, Western Cape, South Africa, 7130
      • Dr JM Engelbrecht Trial Site
    • Worcester, Western Cape, South Africa, 6850
      • Clinical Projects Research SA (PTY) LTD
• Ukraine
  • Dnipro, Ukraine, 49069
    • Communal Noncommercial Profit "Clinical City Hospital 16 of Dnipro Regional Council"
  • Kharkiv, Ukraine, 61096
    • CNE of Kharkov RC Reg Cl Infectious Hospital
  • Kremenchuk, Ukraine, 39623
    • Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1"
  • Odesa, Ukraine, 65026
    • City Clinical infectious Hospital
  • Rivne, Ukraine, 33017
    • Municipal Non-Profit Enterprise Central City Hospital Of Rivne City Council
  • Vinnytsia, Ukraine, 21029
    • CCH #1 Vinnytsia M.I.Pyrogov NMU Ch of Infectious Diseases
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group Llc
  • California
    • Bakersfield, California, United States, 93309
      • Good Samaritan Hospital
    • Chula Vista, California, United States, 91910
      • Sharp Chula Vista Medical Center
    • El Centro, California, United States, 92243
      • El Centro Regional Medical Center
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Riverside, California, United States, 92501-4135
      • Riverside Community Hospital
    • S. El Monte, California, United States, 91733
      • National Institute Of Clinical Research
    • Sacramento, California, United States, 95817
      • University of California Davis Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Shands Hospital
    • Jacksonville, Florida, United States, 32216
      • Memorial Hospital Jacksonville
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa
  • Michigan
    • Detroit, Michigan, United States, 48235
      • Sinai Grace Hospital
    • Detroit, Michigan, United States, 48201-2018
      • Harper University Hospital
    • Royal Oak, Michigan, United States, 48073
      • Detroit Receiving Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • University of Tennessee Health Sciences Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Medical City Ft. Worth
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
    • Sherman, Texas, United States, 75090
      • Texoma Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Apremilast + Standard of Care; Participants will be 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, death, or discontinuation of investigational product, whichever occurred first.	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.; Drug: Apremilast; Apremilast administered orally as a tablet.; Other Names: Otezla
PLACEBO_COMPARATOR: Apremilast Placebo + Standard of Care; Participants will be randomized to receive matching placebo to apremilast orally twice a day in addition to standard of care treatment for 14 days or until hospital discharge, death, or discontinuation of investigational product, whichever occurred first.	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.; Drug: Apremilast placebo; Matching apremilast placebo administered orally as a tablet.
EXPERIMENTAL: Lanadelumab + Standard of Care; Participants will be 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.	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.; Drug: Lanadelumab; Lanadelumab administered as an intravenous (IV) infusion.; Other Names: TAK-743; TAKHZYRO™
PLACEBO_COMPARATOR: Lanadelumab Placebo + Standard of Care; Participants will be randomized to receive placebo to lanadelumab by intravenous infusion on Day 1, and a second dose administered on Day 4 in addition to standard of care.	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.; Drug: Lanadelumab placebo; Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.
EXPERIMENTAL: Zilucoplan + Standard of Care; Participants will be 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.	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.; Drug: Zilucoplan; Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.
PLACEBO_COMPARATOR: Zilucoplan Placebo + Standard of Care; Participants will be randomized to receive placebo to 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.	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.; Drug: Zilucoplan placebo; Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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)

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 24, 2020
• Primary Completion (ACTUAL): August 3, 2021
• Study Completion (ACTUAL): August 3, 2021

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (ACTUAL): October 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Thalidomide; Antibodies, Monoclonal; Apremilast
• Other Study ID Numbers: COV-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No