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

• Recombinant Human Keratinocyte Growth Factor-2 for Inhalation (Lyophilized Powder) (Drug): The investigational drug will be reconstituted with water for injection to a concentration of 1 mg/mL, and then administered via a single-use bronchoscopic imaging catheter.

Primary outcomes

• Incidence of adverse events (AE) and incidence of adverse drug reactions (ADR); [At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.]
• Incidence of serious adverse events (SAE) [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 [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 [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 [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
• Incidence of airway spasm (increased airway resistance) caused by local drug stimulation [At Baseline, Day 1, Day 2, Day 3, Day 5, Day 7, Day 14 and Day 28.]

Secondary outcomes

• 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]: Score (scale range: 0-4; higher scores indicate more severe lung injury)
• Change from baseline in Radiographic Assessment of Lung Edema (RALE) score; [at Day 3, Day 7, Day 14, and Day 28]: Score (scale range: 0-48; higher scores indicate a worse outcome);
• 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]: Ventilator-free days at Day 28 (unit: days; higher scores indicate a better outcome).
• Systemic evaluation measures: Non-ICU hospital stay days at Day 28 [at Day 28.]: Non-ICU hospital stay days at Day 28 (unit: days; higher scores indicate a better outcome as applicable).
• Systemic evaluation measures: Non-hospitalization days at Day 28 [at Day 28]: Non-hospitalization days at Day 28 (unit: days; higher scores indicate a better outcome).

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Aged ≥18 years and <80 years, male or female.
2. Definite diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin Definition.
3. Patients with PaO₂/FiO₂ < 200 mmHg and receiving invasive mechanical ventilation via endotracheal intubation.
4. Diagnosis of ARDS confirmed no more than 72 hours prior to enrollment.
5. 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.
6. 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.

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Exclusion Criteria:

1. Use of inhaled pulmonary vasodilators (e.g., nitric oxide or prostaglandins).
2. Current receipt or planned receipt of extracorporeal membrane oxygenation (ECMO) during the study period.
3. Expected survival < 3 months due to causes other than respiratory failure.
4. 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.
5. 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.
6. History of severe allergic reaction, or known allergy or hypersensitivity to any component of the investigational product.
7. Breastfeeding or pregnant women.
8. Participation in any drug clinical trial within 3 months prior to enrollment.
9. Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.

• Yuanlin Song, Study director, Shanghai Zhongshan Hospital
• Jing Bi, Principal investigator, Shanghai Zhongshan Hospital