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Completed

NCT Number: NCT04590586

Study 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.

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital San Juan de Dios, Ramos Mejía, Buenos Aires, Argentina

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About this study

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:

  • 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 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Standard of care

Drug

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

Drug

Apremilast administered orally as a tablet.

Other names: Otezla

Apremilast placebo

Drug

Matching apremilast placebo administered orally as a tablet.

Lanadelumab

Drug

Lanadelumab administered as an intravenous (IV) infusion.

Other names: TAKHZYRO™, TAK-743

Lanadelumab placebo

Drug

Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.

Zilucoplan

Drug

Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

Zilucoplan placebo

Drug

Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

Primary outcomes

  1. Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

    Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

    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.

  2. Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

    Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

    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.

  3. Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

    Time frame: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

    Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29.

    The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.

Secondary outcomes

  1. Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29

    Time frame: 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.

  2. 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

    Time frame: Baseline (Day 1) and Day 29

    Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

    The clinical severity status 8-point ordinal scale scores are:

    • 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

  3. Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29

    Time frame: Day 1 to Day 29

    All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

  4. Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29

    Time frame: Day 8, Day 15, and 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

    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.

  5. Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29

    Time frame: Day 2 to Day 29

    The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

    The clinical severity status 8-point ordinal scale scores are:

    • 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

  6. Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

  7. Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

  8. Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29

    Time frame: Day 8, Day 15, and Day 29

    Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

    Clinical severity status 8-point ordinal scale:

    • 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

  9. Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery

    Time frame: Day 60

    Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

    Clinical severity status 8-point ordinal scale:

    • 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

  10. Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: From first dose of study drug to end of study (Day 60)

    An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A Serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

    The Investigator assessed the intensity of each AE according to the Common Terminology Criteria for Adverse Events (CTCAE):

    • Grade 1 Mild; asymptomatic or mild symptoms;
    • Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
    • Grade 3 Severe or medically significant, not immediately life-threatening;
    • Grade 4 Life-threatening; urgent intervention indicated;
    • Grade 5 Death due to AE.

  11. Apremilast Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29

    Time frame: 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.

  12. 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

    Time frame: Baseline (Day 1) and Day 29

    Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

    The clinical severity status 8-point ordinal scale scores are:

    • 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

  13. Apremilast Sub-protocol: Percentage of Participants Who Died Before or on Day 29

    Time frame: Day 1 to Day 29

    All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

  14. Apremilast Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29

    Time frame: Day 8, Day 15, and 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

    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.

  15. Apremilast Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29

    Time frame: Day 2 to Day 29

    The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

    The clinical severity status 8-point ordinal scale scores are:

    • 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

  16. Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

  17. Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

  18. Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29

    Time frame: Day 8, Day 15, and Day 29

    Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

    Clinical severity status 8-point ordinal scale:

    • 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

  19. Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery

    Time frame: Day 60

    Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

    Clinical severity status 8-point ordinal scale:

    • 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

  20. Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: From first dose of study drug to end of study (Day 60)

    An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

    The Investigator assessed the intensity of each AE according to the CTCAE grades:

    • Grade 1 Mild; asymptomatic or mild symptoms;
    • Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
    • Grade 3 Severe or medically significant, not immediately life-threatening;
    • Grade 4 Life-threatening; urgent intervention indicated;
    • Grade 5 Death due to AE.

  21. Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29

    Time frame: 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.

  22. 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

    Time frame: Baseline (Day 1) and Day 29

    Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

    The clinical severity status 8-point ordinal scale scores are:

    • 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

  23. Zilucoplan Sub-protocol: Percentage of Participants Who Died Before or on Day 29

    Time frame: Day 1 to Day 29

    All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

  24. Zilucoplan Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29

    Time frame: Day 8, Day 15, and 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

    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.

  25. Zilucoplan Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-Point Ordinal Scale From Baseline to Day 29

    Time frame: Day 2 to Day 29

    The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale scores, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care were considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

    The clinical severity status 8-point ordinal scale scores scores are:

    • 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

  26. Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

  27. Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29

    Time frame: Day 1 to Day 29

    Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

  28. Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29

    Time frame: Day 8, Day 15, and Day 29

    Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

    Clinical severity status 8-point ordinal scale:

    • 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

  29. Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery

    Time frame: Day 60

    Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

    Clinical severity status 8-point ordinal scale:

    • 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

  30. Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events

    Time frame: From first dose of study drug to end of study (Day 60)

    An adverse event is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

    The Investigator assessed the intensity of each AE according to the CTCAE grades:

    • Grade 1 Mild; asymptomatic or mild symptoms;
    • Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
    • Grade 3 Severe or medically significant, not immediately life-threatening;
    • Grade 4 Life-threatening; urgent intervention indicated;
    • Grade 5 Death due to AE.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study title

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

Acronym: COMMUNITY

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Oct 19, 2020
Registry last updated
Jun 29, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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