A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 227
- 试验地点
- 29
- 主要终点
- Incidence of Mortality
研究概览
简要总结
Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.
详细描述
Gimsilumab is a monoclonal antibody against granulocyte macrophage-colony stimulating factor (GM-CSF), which is a myeloid cell growth factor and pro- inflammatory cytokine. Late stages of COVID-19 can be marked by a "cytokine storm" and the overactivation of inflammatory myeloid cells that infiltrate and damage tissue, such as the lungs. Inhibition of GM-CSF may be able to reverse this pathology. The anti-GM-CSF mechanism is distinct from antiviral therapeutic mechanisms and may provide synergistic effects when used in combination.
Study KIN-1901-2001 will consist of a 2-week treatment period (last dose Day 8, if administered) and a 22-week follow-up period, for a total study duration of 24 weeks for each subject. A total of 270 subjects (135 subjects per arm) who have a confirmed diagnosis of COVID-19 with clinical evidence of acute lung injury or ARDS will be entered into the trial.
Subjects will receive a 400 mg dose of gimsilumab on Day 1 and a 200 mg dose of gimsilumab on Day 8, or matching placebo (saline solution) on Day 1 and on Day 8. The Day 8 dose will be omitted if the subject is discharged from the hospital prior to the dose or is no longer in need of supplemental oxygen or ventilatory support for >48 hours.
The primary objective of Study KIN-1901-2001 is to evaluate the impact of IV treatment with gimsilumab on mortality in subjects with lung injury or ARDS secondary to COVID-19.
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
- •Male or non-pregnant female age ≥18 years, inclusive
- •Subject (or legally authorized representative) is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form
- •Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other approved clinical testing prior to randomization
- •Radiographic evidence of bilateral infiltrates
- •Subject requires high-flow oxygen or meets clinical classification for ARDS
- •Elevated serum CRP or ferritin
- •Subjects who have been treated with convalescent plasma (CP) prior to enrollment are eligible if the subject continues to meet all inclusion criteria at screening
- •The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the subject continues to meet all inclusion criteria at screening
- •Additional inclusion criteria are detailed in the protocol
排除标准
- •Evidence of life-threatening dysrhythmia or cardiac arrest on presentation
- •Intubated >72 hours
- •Absolute neutrophil count < 1,000 per mm3
- •Platelet count < 50,000 per mm3
- •AST or ALT > 5X upper limit of normal
- •eGFR <30 mL/min/1.73m2 or requiring hemofiltration or dialysis
- •History of known anti-GM-CSF autoantibodies or pulmonary alveolar proteinosis
- •Severe chronic respiratory disease (e.g., COPD, PAH, IPF, ILD) requiring supplemental oxygen therapy or mechanical ventilation pre-hospitalization (e.g., prior to COVID-19 diagnosis)
- •Use of any immunomodulatory biologic, cell therapy, or small molecule JAK inhibitor within past 7 days or 5 half lives or planned use of any of these agents unless approved by medical monitor
- •Chronic (>4 weeks) use of corticosteroids >10mg/day of prednisone or equivalent
- •Known or suspected active and untreated TB, HIV, hepatitis B or C infection
- •Additional exclusion criteria are detailed in the protocol.
研究组 & 干预措施
Gimsilumab
Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
干预措施: Gimsilumab (Drug)
Placebo
Normal saline on Day 1 Normal saline on Day 8
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Mortality
时间窗: Day 43
"Incidence" is defined as the percent of subjects that died by Day 43
次要结局
- Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation(Day 29)
- Number of Ventilator-free Days(Baseline to Day 29)
- Time to Hospital Discharge(Baseline to Day 43)