A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia
试验速览
- 阶段
- 3 期
- 入组人数
- 520
- 试验地点
- 27
- 主要终点
- Ventilator-free Survival
研究概览
简要总结
The primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome (CRS) and improve ventilator-free survival in hospitalized subjects with severe or critical COVID-19 pneumonia.
详细描述
In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. The mortality rate for hospitalized COVID-19 patients remains unacceptably high, particularly in patients who progress to invasive mechanical ventilation (IMV). This randomized, double-blind, multicenter, placebo-controlled pivotal phase 3 trial will evaluate the impact of lenzilumab (anti-human GM-CSF monoclonal antibody) on ventilator-free survival in hospitalized, hypoxic patients with COVID-19. The study is also designed to evaluate other key endpoints, including ventilator-free days, duration of ICU stay, incidence of IMV, ECMO and/or death, time to death, all-cause mortality and time to recovery.
Approximately 516 patients will be randomized to receive lenzilumab + SOC vs. placebo + SOC in a 1:1 ratio.
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)
盲法说明
Double-Blind
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 or older who are capable of providing informed consent or have a proxy capable of giving consent for them
- •Virologic confirmation of SARS-CoV-2 infection via any FDA authorized diagnostic test for SARS-CoV-2
- •Pneumonia diagnosed by Chest X-ray or Computed Tomography revealing infiltrates consistent with pneumonia
- •SpO2 ≤ 94% on room air and/or require low-flow supplemental oxygen and/or require high-flow oxygen support or NIPPV
- •Hospitalized, not requiring invasive mechanical ventilation during this hospitalization
- •Have not participated in other clinical trial for COVID-19 using an immunomodulatory monoclonal antibody or kinase inhibitor (use of remdesivir, corticosteroids, convalescent plasma, hydroxychloroquine or chloroquine is permitted)
- •Females of childbearing potential must have a negative serum or urine pregnancy test
排除标准
- •Requiring invasive mechanical ventilation or extracorporeal membrane oxygenation prior to randomization
- •Confirmed diagnosis of bacterial pneumonia or other active/uncontrolled fungal or viral infections at screening/baseline
- •Known active tuberculosis (TB), history of incompletely treated TB or suspected or known extrapulmonary TB
- •Currently receiving treatment for hepatitis A, hepatitis B, hepatitis C or HIV infection
- •History of pulmonary alveolar proteinosis (PAP)
- •Women of childbearing potential who are pregnant or breastfeeding
- •Known hypersensitivity to lenzilumab or any of its components
- •Use of any FDA authorized anti-IL-6 (e.g., tocilizumab, sarilumab, sitlukimab), anti-IL-1 (e.g., anakinra, canakinumab), kinase inhibitor (e.g., baracitinib, ibrutinib, acalabrutinib), or neutralizing monoclonal antibody (e.g. bamlanivimab or casirivimab/imdevimab) therapy to treat COVID-19 within 8 weeks prior to randomization
- •Use of GM-CSF agents (e.g., sargramostim) within prior 2 months of randomization
- •Expected survival < 48h in the opinion of the investigator
- •Any condition that, in the opinion of the investigator, is likely to interfere with the safety and efficacy of the study treatment or puts the patient at unacceptably high risk from the study
研究组 & 干预措施
Lenzilumab Arm
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
干预措施: Lenzilumab (Biological)
Lenzilumab Arm
Participants will receive IV infusion of lenzilumab upon randomization at a pre-specified dosing interval and continued administration of standard of care
干预措施: Standard of Care (Drug)
Placebo Arm
Participants will receive IV infusion of preservative-free 0.9% sodium chloride solution upon randomization matched to lenzilumab at same pre-specified dosing interval and continued administration of standard of care
干预措施: Standard of Care (Drug)
结局指标
主要结局
Ventilator-free Survival
时间窗: Up to Day 28
次要结局
- Ventilator-free Days(Up to Day 28)
- Duration of Intensive Care Unit (ICU) Stay(Up to Day 28)
- Percentage of Participants Experiencing Serious Adverse Events(Up to Day 60)
- Incidence of Invasive Mechanical Ventilation, ECMO and/or Death(Up to Day 28)
- Time to Death(Up to Day 28)
- All-cause Mortality(Day 28)
- Time to Recovery(Up to Day 28)
- Incidence of severe acute respiratory distress syndrome (ARDS)(Up to Day 28)
- Proportion of Subjects Discharged from Hospital(Up to Day 60)
- Duration of Hospitalization(Up to Day 28)
- Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale(Up to Day 28)
- Number of Subjects Alive and Off Oxygen(Up to Day 60)
- Percentage of Participants Experiencing Adverse Events(Up to Day 60)
- Time to improvement in oxygenation for > 48 hours(Up to Day 28)
- Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)(Up to Day 28)
- Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours(Up to Day 28)
- Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale(Up to Day 28)
- Duration of Time on Low-flow or High-flow Supplemental Oxygen(Up to Day 28)