A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 814
- 试验地点
- 32
- 主要终点
- Cohort 1, Phase 2: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
研究概览
简要总结
Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).
详细描述
The Phase 2 portion of the study will evaluate the efficacy and safety of 2 dose levels of mavrilimumab relative to placebo (standard of care) in participants who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with x-ray/computed tomography (CT) evidence of bilateral pneumonia and active or recent signs of hyperinflammation (fever or clinical laboratory results indicative of hyper-inflammation). The Phase 3 portion is intended to confirm Phase 2 efficacy and safety findings. In both Phase 2 and Phase 3, participants will be enrolled into 2 cohorts: Cohort 1 will include non-mechanically ventilated, hospitalized participants who require supplemental oxygen to maintain oxygen saturation (SpO2) ≥ 92% (ie, "non-mechanically ventilated" participants); Cohort 2 will include hospitalized participants for whom mechanical ventilation was recently initiated (ie, "mechanically ventilated" participants). Following Screening, enrolled participants in each cohort will be randomized 1:1:1 to receive one of 2 mavrilimumab dose levels, or placebo as a single intravenous (IV) infusion (Day 1). Participants will undergo primary study assessments through Day 29 and will be followed for safety through Day 90.
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
- Double (Participant, Investigator)
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
- •Subject (or legally authorized representative) is able and willing to provide informed consent, which includes compliance with study requirements and restrictions listed in the consent form. Consent must be performed per institutional regulations.
- •Age of ≥ 18 years
- •Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization
- •Hospitalized for SARS-CoV-2 (2019-nCoV)
- •Bilateral pneumonia on chest x-ray or computed tomography
- •Clinical laboratory results indicative of hyper-inflammation within 7 days prior to randomization
- •Cohort 1: Receiving any form of non-invasive ventilation OR oxygenation to maintain SpO2 ≥ 92% and non-mechanically ventilated (examples include nasal cannula, face mask, venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation)
- •Cohort 2: Recently ventilated with mechanical ventilation beginning within 48 hours prior to randomization
排除标准
- •Onset of COVID-19 symptoms > 14 days prior to randomization
- •Hospitalized > 7 days prior to randomization
- •Need for invasive mechanical ventilation (Only for Cohort 1)
- •Need for ECMO
- •Serious prior or concomitant illness that in the opinion of the Investigator precludes the subject from enrolling in the trial
- •Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12 months, non-cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil (MMF), or other immunosuppressant (except for corticosteroids) within 4 weeks prior to randomization. Medications that become standard of care for COVID-19 and/or receive emergency use authorization may be allowed after discussion with the medical monitor.
- •If subject is receiving or has received hydroxychloroquine within 3 months prior to screening visit, a corrected QT interval by Federicia method (QTcF) on Screening electrocardiogram (ECG) ≥500ms is exclusionary. If subject has a pacemaker, this criterion does not apply.
- •Enrolled in another investigational study of a medical intervention within 30 days prior to randomization. Participation in open label trials involving investigational treatments for COVID-19 may be allowed upon approval by the Sponsor.
- •Life expectancy less than 48 hours, in the opinion of the Investigator
- •Known human immunodeficiency virus infection (regardless of immunological status), known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus positivity
研究组 & 干预措施
Placebo (Cohort 1)
Non-mechanically ventilated participants administered placebo as a single IV infusion
干预措施: Placebo (Other)
Placebo (Cohort 2)
Mechanically ventilated participants administered placebo as a single IV infusion
干预措施: Placebo (Other)
6 mg/kg (Cohort 2)
Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
干预措施: mavrilimumab (Drug)
10 mg/kg (Cohort 2)
Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
干预措施: mavrilimumab (Drug)
6 mg/kg (Cohort 1)
Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
干预措施: mavrilimumab (Drug)
10 mg/kg (Cohort 1)
Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
干预措施: mavrilimumab (Drug)
结局指标
主要结局
Cohort 1, Phase 2: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
时间窗: Day 29
Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status was evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Participants whose clinical outcome met a NIAID score of 2 were considered as using mechanical ventilation. The NIAID score is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive 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.
Cohort 1, Phase 3: Percentage of Participants Alive and Free of Mechanical Ventilation at Day 29
时间窗: Day 29
Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Mechanical ventilation status was evaluated based on the National Institute of Allergy and Infectious Diseases (NIAID) clinical outcome 8-point ordinal scale. Participants whose clinical outcome met a NIAID score of 2 were considered as using mechanical ventilation. The NIAID score is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive 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.
Cohort 2, Phase 2: Percentage of Participants Who Died by Day 29
时间窗: Day 29
Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.
Cohort 2, Phase 3: Percentage of Participants Who Died by Day 29
时间窗: Day 29
Defined as the proportion of subjects with mechanical ventilation who have died by Day 29.
次要结局
- Phase 2, Cohort 1: Time to Return to Room Air or Discharge by Day 29(Day 29)
- Phase 2, Cohort 2: Time to 1-Point Clinical Improvement by Day 29(Day 29)
- Phase 2, Cohort 1: Percentage of Participants Who Die by Day 29(Day 29)
- Phase 3, Cohort 1: Percentage of Participants Who Died at Day 29(Day 29)
- Cohort 1, Phase 2: Time to 2-point Clinical Improvement by Day 29(Day 29)
- Phase 3, Cohort 1: Ventilation-Free Survival (Time to Ventilation or Death) by Day 29(Day 29)
- Phase 3, Cohort 1: Overall Survival by Day 29(Day 29)
- Phase 3, Cohort 2: Time to 1-point Clinical Improvement by Day 29(Day 29)