Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 515
- 试验地点
- 59
- 主要终点
- Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •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).
研究组 & 干预措施
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.
干预措施: Standard of care (Drug)
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.
干预措施: Apremilast (Drug)
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.
干预措施: Standard of care (Drug)
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.
干预措施: Apremilast placebo (Drug)
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.
干预措施: Standard of care (Drug)
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.
干预措施: Lanadelumab (Drug)
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.
干预措施: Standard of care (Drug)
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.
干预措施: Lanadelumab placebo (Drug)
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.
干预措施: Standard of care (Drug)
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.
干预措施: Zilucoplan (Drug)
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.
干预措施: Standard of care (Drug)
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.
干预措施: Zilucoplan placebo (Drug)
结局指标
主要结局
Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
时间窗: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.
Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
时间窗: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.
Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29
时间窗: 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.
次要结局
- Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29(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(Baseline (Day 1) and Day 29)
- Lanadelumab Sub-protocol: Percentage of Participants Who Died 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(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(Day 2 to Day 29)
- Lanadelumab Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29(Day 1 to Day 29)
- Lanadelumab Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29(Day 1 to Day 29)
- Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29(Day 8, Day 15, and Day 29)
- Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery(Day 60)
- Lanadelumab Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(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(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(Baseline (Day 1) and Day 29)
- Apremilast Sub-protocol: Percentage of Participants Who Died 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(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(Day 2 to Day 29)
- Apremilast Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29(Day 1 to Day 29)
- Apremilast Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29(Day 1 to Day 29)
- Apremilast Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery at Days 8, 15, and 29(Day 8, Day 15, and Day 29)
- Apremilast Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery(Day 60)
- Apremilast Sub-protocol: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(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(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(Baseline (Day 1) and Day 29)
- Zilucoplan Sub-protocol: Percentage of Participants Who Died 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(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(Day 2 to Day 29)
- Zilucoplan Sub-protocol: Number of Intensive Care Unit (ICU) Days From Day 1 Through Day 29(Day 1 to Day 29)
- Zilucoplan Sub-protocol: Number of Invasive Mechanical Ventilator Days From Day 1 Through Day 29(Day 1 to Day 29)
- Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Clinical Recovery by Days 8, 15, and 29(Day 8, Day 15, and Day 29)
- Zilucoplan Sub-protocol: Percentage of Participants Who Achieved Sustained Clinical Recovery(Day 60)
- Zilucoplan Sub-protocol: Number of Participants With Treatment-emergent Adverse Events(From first dose of study drug to end of study (Day 60))