A Single Dose, Dose Escalation Clinical Trial on the Safety, Tolerability and Efficacy of Lyophilized Powder for Inhalation of Recombinant Human Keratinocyte Growth Factor-2 (Rh-KGF-2) in The Treatment of Patients With Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of airway spasm (increased airway resistance) caused by local drug stimulation
研究概览
简要总结
This study is a randomized, blank-controlled, open-label, single-dose, dose-escalation clinical study of rhKGF-2 in patients with ARDS.
The trial is designed with three dose groups (5 mg, 10 mg, and 15 mg), which will be escalated sequentially from the lowest dose group to the highest dose group. Each dose group will enroll 8 subjects, randomized in a 6:2 ratio according to the order of enrollment, to receive either the corresponding dose of rhKGF-2 (6 subjects) or serve as a blank control (2 subjects). Each subject will receive a single dose, administered once via a disposable bronchoscopic catheter.
All subjects will receive the trial intervention on top of standard ARDS treatment (see Concomitant Medications for details). Following the completion of drug administration, subjects will enter a 28-day follow-up period. Outcome measures include adverse events (AE), vital signs, laboratory parameters, oxygenation index (PFR), chest imaging changes, etc., to evaluate the safety, tolerability, and efficacy of the treatment.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥18 years and <80 years, male or female.
- •Definite diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin Definition.
- •Patients with PaO₂/FiO₂ < 200 mmHg and receiving invasive mechanical ventilation via endotracheal intubation.
- •Diagnosis of ARDS confirmed no more than 72 hours prior to enrollment.
- •No plan for parenthood within 1 year and agree to take effective contraceptive measures during the study period. Female participants of childbearing potential must have a negative serum pregnancy test.
- •The subject fully understands the purpose of the study, as well as the nature, methods, and potential reactions of the investigational drug. The subject voluntarily signs the informed consent form to participate in the study and agrees to comply with the requirements of the study protocol. If the subject is unable to provide consent or has limited capacity to consent, consent must be obtained from the subject's legal guardian.
排除标准
- •Use of inhaled pulmonary vasodilators (e.g., nitric oxide or prostaglandins).
- •Current receipt or planned receipt of extracorporeal membrane oxygenation (ECMO) during the study period.
- •Expected survival < 3 months due to causes other than respiratory failure.
- •Cerebrovascular or cardiovascular events within 3 months prior to study drug administration, including unstable angina, congestive heart failure, myocardial infarction within the past 12 months, hemodynamic instability, known left ventricular ejection fraction (LVEF) < 40%, or clinically significant arrhythmia or conduction abnormality.
- •Inability to tolerate single-use bronchoscopic imaging catheter examination, including but not limited to the following: active massive hemoptysis; severe hypertension and arrhythmia; myocardial infarction or unstable angina within 4-6 weeks prior to screening; severe cardiac dysfunction; uncorrectable bleeding tendency (platelet count < 60 × 10⁹/L), such as severe coagulation disorders, uremia, or severe pulmonary hypertension; severe superior vena cava syndrome; suspected aortic aneurysm; multiple pulmonary bullae.
- •History of severe allergic reaction, or known allergy or hypersensitivity to any component of the investigational product.
- •Breastfeeding or pregnant women.
- •Participation in any drug clinical trial within 3 months prior to enrollment.
- •Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.
研究组 & 干预措施
15 mg rhKGF-2
干预措施: Recombinant Human Keratinocyte Growth Factor-2 for Inhalation (Lyophilized Powder) (Drug)
Blank Control for 15 mg Cohort
Blank Control for 5 mg Cohort
10 mg rhKGF-2
干预措施: Recombinant Human Keratinocyte Growth Factor-2 for Inhalation (Lyophilized Powder) (Drug)
5 mg rhKGF-2
干预措施: Recombinant Human Keratinocyte Growth Factor-2 for Inhalation (Lyophilized Powder) (Drug)
Blank Control for 10 mg Cohort
结局指标
主要结局
Incidence of airway spasm (increased airway resistance) caused by local drug stimulation
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Incidence of adverse events (AE) and incidence of adverse drug reactions (ADR);
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Incidence of serious adverse events (SAE)
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Various laboratory test parameters：White blood cell (WBC) count
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Unit of measure: 3.5 - 9.5 × 10\^9/L
Various Laboratory test parameters: Serum creatinine (Cr) level
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Unit of measure: 44 -115 μmol/L
Various laboratory test parameters: Total Bilirubin
时间窗: At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.
Unit of measure: 3.4-20.4 umol /L
次要结局
- Improvement rate of oxygenation indexPaO₂/FiO₂ ratio (PFR)(at Day 3 and Day 7)
- PaO₂/FiO₂ ratio (PFR) and its change from baseline(at Day 3, Day 5, and Day 7)
- Number of days from baseline to first PaO₂/FiO₂ ratio (PFR) > 300 mmHg or liberation from mechanical ventilation for at least 12 consecutive hours(From baseline to first PFR > 300 mmHg or liberation from mechanical ventilation for at least 12 consecutive hours)
- Change from baseline in the Murray Lung Injury Score(LIS).(at Day 7)
- Change from baseline in Radiographic Assessment of Lung Edema (RALE) score;(at Day 3, Day 7, Day 14, and Day 28)
- Proportion of patients with improvement in ARDS severity grade(at Day 7 and Day 14)
- Proportion of patients with progression in ARDS severity grade(at Day 7 and Day 14)
- All-cause mortality(at Day 28)
- Systemic evaluation measures: Ventilator-free days at Day 28(at Day 28)
- Systemic evaluation measures: Non-ICU hospital stay days at Day 28(at Day 28.)
- Systemic evaluation measures: Non-hospitalization days at Day 28(at Day 28)
研究者
Song Yuanlin
Director of Department of Pulmonary and Critical Care Medicine
Shanghai Zhongshan Hospital