Phase 2, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study of Anti-CD14 Treatment With a Recombinant Chimeric Monoclonal Antibody (IC14) in Hospitalized Patients With Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Day 4 Oxygenation Index
研究概览
简要总结
Hospitalized patients with ARDS will be randomized to intravenous treatment with a monoclonal antibody against CD14, called IC14, or placebo. They will be followed for 28 days.
The primary outcome is the day 4 oxygenation index assessed as a continuous measure.
详细描述
This is a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of anti-CD14 treatment with a recombinant chimeric monoclonal antibody (IC14) in hospitalized patients with Acute Respiratory Distress Syndrome (ARDS). CD14 is a key mediator in recognition of molecular markers of tissue damage (damage-associated molecular patterns, DAMPs) and infection (pathogen-associated molecular patterns, PAMPS).
The primary objective of the study is to determine the efficacy of IC14 in patients hospitalized with ARDS for reducing the severity of lung injury as measured by the day 4 Oxygenation Index (OI) assessed as a continuous measure (mean airway pressure x fraction of inspired oxygen [FiO2] x 100/partial pressure of oxygen [PaO2]). OI captures severity of hypoxemia and concurrent intensity of ventilatory support.
Secondary objectives include determining whether IC14 reduces the systemic and alveolar inflammatory response, and improves indices of oxygenation and illness severity. Exploratory endpoints include determining the effect of CD14 blockade on duration of mechanical ventilation and mortality in patients hospitalized with ARDS. Pharmacokinetic [PK]/Pharmacodynamic [PD] endpoints include determining day 4 IC14 levels in bronchoalveolar fluid (BALF) vs. serum, and determining the feasibility of measuring blood presepsin levels, a CD14-pathway specific biomarker for rapid assessment.
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)
盲法说明
Identical-appearing placebo prepared by research pharmacist
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
- •Patients may be included in the study only if they meet all the following criteria:
- •Adult patients (18+) on mechanical ventilations with acute respiratory distress syndrome (ARDS) by Berlin Criteria (≤48 hours)
- •P:F ratio < 300
- •Positive end-expiratory pressure (PEEP) ≥5 cm H2O
- •Bilateral opacities on chest x-ray or chest computerized tomography (CT)-- not fully explained by effusions, lobar/lung collapse, or nodules
- •Respiratory failure not fully explained by cardiac failure or fluid overload
- •Within 1 week of known clinical insult or new or worsening respiratory symptoms
- •i. Common Risk Factors for ARDS: Pneumonia, aspiration, inhalation injury, pulmonary contusion, pulmonary vasculitis, drowning, non-pulmonary sepsis, major trauma, pancreatitis, severe burns, non-cardiogenic shock, drug overdose, multiple transfusions
- •Patient or Legal authorized representative able to understand and give written informed consent
排除标准
- •An individual fulfilling any of the following criteria should be excluded from enrollment in the study:
- •Significant pre-existing organ dysfunction prior to hospitalization
- •Lung: Currently receiving home oxygen therapy as documented in medical record
- •Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record
- •Renal: End-stage renal disease requiring renal replacement therapy or estimated glomerular filtration rate (eGFR) <30 mL/min.
- •Liver: Severe chronic liver disease defined as Child-Pugh Class C or hepatic transaminases >5 times upper limit of normal
- •Hematologic: Baseline platelet count <50,000/mm3
- •Presence of co-existing infection, including, but not limited to:
- •HIV infection not virally suppressed and with pre-hospitalization CD4 counts ≤ 500 cell/mm3
- •Active tuberculosis or a history of inadequately treated tuberculosis
- •Active hepatitis B or hepatitis C viral infection
- •Current treatment, or treatment within 30 days or five half-lives (whichever is longer) with etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab (Cimzia®), golimumab (Simponi®), anakinra (Kineret®), rilonacept (Arcalyst®), tocilizumab (Actemra®), sarilumab (Kevzara®), siltuximab (Sylvant®), or other potent immunosuppressant or immunomodulatory drugs or treatments
- •Receiving comfort measures only
- •Requiring >2 vasopressors
- •History of hypersensitivity or idiosyncratic reaction to IC14
- •Women who are currently breastfeeding
- •Bronchoscopy safety exclusions
- •P:F <100 on 100% FiO2
- •Mean pulmonary artery pressure > 55 mmHg
- •Marked cardiovascular instability (Mean arterial pressure <55 mmHg with vasopressor support)
- •Intracranial pressure ≥20 mmHg
- •Acute ischemic heart disease (unstable angina or ST-elevation myocardial infarction or Type 1 non-ST-elevation myocardial infarction)
- •Supported on extracorporeal membrane oxygenation
- •Endotracheal tube <6.5 mm
研究组 & 干预措施
Identical-appearing placebo
Sterile normal saline
干预措施: Placebo (Other)
IC14 (atibuclimab)
IC14 (atibuclimab) is a recombinant monoclonal antibody against human CD14
干预措施: Atibuclimab (Biological)
结局指标
主要结局
Day 4 Oxygenation Index
时间窗: Day 1 through Day 4
(mean airway pressure x fraction of inspired oxygen \[FiO2\] x100)/ partial pressure of oxygen \[PaO2\]
次要结局
- Biomarkers of injury and inflammation measured in bronchoalveolar lavage fluid(Day 4)
- Biomarkers of injury and inflammation measured in plasma(Day 4)
- P:F ratio(Days 4, 7, and 14)
- Oxygenation index(Days 7 and 14)
- Oxygen saturation index(Days 4, 7, and 14)
- S:F ratio(Days 4, 7, and 14)
- Sequential Organ Failure Assessment (SOFA) Score (range 0 [best] to 24 [worst])(Days 4, 7, and 14)
- Time to blood presepsin level(Days 0-4)
- Cumulative incidence of run failures(Days 0-1)
- Cumulative incidence of protocol-specified exempt serious events(Days 1-28)
- Cumulative incidence of grade 3 and 4 clinical and laboratory adverse events(Days 1-28)
- Cumulative incidence of serious adverse events(Days 1-28)
- Cumulative incidence of adverse events of special interest(Days 1-28)