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

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ClinicalTrials.gov Identifier: NCT04590586
Recruitment Status : Completed
First Posted : October 19, 2020
Last Update Posted : November 23, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Standard of care Drug: Apremilast Drug: Apremilast placebo Drug: Lanadelumab Drug: Lanadelumab placebo Drug: Zilucoplan Drug: Zilucoplan placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 516 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 24, 2020
Actual Primary Completion Date : August 3, 2021
Actual Study Completion Date : August 3, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Apremilast and standard of care (SoC) 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.

Placebo Comparator: Apremilast placebo and standard of care (SoC) 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 and standard of care (SoC) 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.

Placebo Comparator: Lanadelumab placebo and standard of care (SoC) 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 and standard of care (SoC) 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 and standard of care (SoC) 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.




Primary Outcome Measures :
  1. Time to confirmed clinical recovery [ Time Frame: Baseline (Day 1) to Day 29 ]

    Confirmed clinical recovery means the participant is fit for discharge from hospital. Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29.

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

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities


Secondary Outcome Measures :
  1. Number of participants who achieve oxygen-free recovery at Day 29 [ Time Frame: Day 29 ]
    Oxygen-free recovery is defined as participants who are alive, discharged, and not receiving supplement oxygen

  2. Number of participants who experience ≥2-point improvement from baseline or assessed as fit-for-discharge on the ordinal scale at Day 29 [ Time Frame: Baseline (Day 1) to Day 29 ]

    Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29.

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

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities

  3. Incidence of all-cause mortality [ Time Frame: Baseline (Day 1) to Day 29 ]
    All-cause mortality is death due to any cause.

  4. Distribution of participants across the 8-point ordinal scale of clinical severity status scores at Day 8, Day 15 and Day 29 [ Time Frame: Day 8, Day 15 and Day 29 ]

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

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities

  5. Worst post-baseline score on the 8-point ordinal scale of clinical severity status [ Time Frame: Baseline (Day 1) to Day 29 ]

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

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities

  6. Number of intensive care unit (ICU) days [ Time Frame: Baseline (Day 1) to Day 29 ]
  7. Number of invasive mechanical ventilator days [ Time Frame: Baseline (Day 1) to Day 29 ]
  8. Number of participants who achieve clinical recovery at Day 8, Day 15, and Day 29 [ Time Frame: Day 8, Day 15, and Day 29 ]

    Clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status.

    8-point ordinal scale of clinical severity status scores are

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities

  9. Number of participants who achieve sustained clinical recovery at Day 60 [ Time Frame: Day 60 ]

    Sustained clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status at follow-up visit (Day 60).

    8-point ordinal scale of clinical severity status scores are

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
    3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
    7. Not hospitalized, limitation on activities and/or requiring home oxygen
    8. Not hospitalized, no limitations on activities

  10. Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline (Day 1) 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 the study treatment. A TEAE is an AE that occurs after the use of study treatment.

  11. Number of participants who experience one or more serious adverse events (SAEs) [ Time Frame: Baseline (Day 1) to End of Study (Day 60) ]
    An SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect, or is considered to be serious by the Investigator.

  12. Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade 3 or higher [ Time Frame: Baseline (Day 1) to End of Study (Day 60) ]

    The CTCAE defines grade 3 and above as:

    • Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden).
    • Grade 4: Life-threatening consequences; urgent intervention indicated.
    • Grade 5: Death related to AE.

  13. Number of participants who experience one or more adverse events (AEs) leading to dose modification [ Time Frame: Baseline (Day 1) to End of Study (Day 60) ]
    An adverse event (AE) leading to dose modification is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment that leads to a change in dose of study treatment.

  14. Number of participants who experience one or more adverse events (AEs) leading to discontinuation [ Time Frame: Baseline (Day 1) to End of Study (Day 60) ]
    An adverse event (AE) leading to discontinuation is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment that leads to the participant discontinuing the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (≥18 years of age) with active 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 N. meningitidis or a past history of N. meningitidis (eg, in a complement-deficient patient).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04590586


Locations
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Sponsors and Collaborators
Amgen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04590586    
Other Study ID Numbers: COV-01
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: November 23, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Thalidomide
Apremilast
Antibodies, Monoclonal
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents