A Clinical Trial of Human Umbilical Cord Mesenchymal Stem Cell Injection for the Treatment of Severe Acute Respiratory Distress Syndrome

A Phase I-II, Open-label, Single-arm, Dose-escalation Clinical Trial to Evaluate the Safety and Tolerability of Human Umbilical Cord Mesenchymal Stem Cell Injection in the Treatment of Moderate to Severe Acute Respiratory Distress Syndrome

Primary Objective: To evaluate the safety and tolerability of human umbilical cord mesenchymal stem cell injection in the treatment of moderate/severe acute respiratory distress syndrome.Secondary Objectives: To explore the efficacy and appropriate dosage of human umbilical cord mesenchymal stem cell injection in the treatment of moderate/severe acute respiratory distress syndrome.Exploratory Objective: To explore the immunogenicity and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of a single dose of human umbilical cord mesenchymal stem cell injection in patients with moderate/severe acute respiratory distress syndrome.

Inclusion Criteria:

• Male or female patients aged 18 to 80 years (inclusive).
• Diagnosis of moderate or severe Acute Respiratory Distress Syndrome (ARDS) according to A New Global Definition of Acute Respiratory Distress Syndrome, with an infectious etiology.
• No improvement after 24 hours of conventional clinical treatment (defined as a persistent PaO₂/FiO₂ ratio ≤200 mmHg or a decrease from >200 mmHg to ≤200 mmHg after 24 hours of conventional supportive therapy; for severe ARDS, this assessment period may be shortened to 8 hours).
• Ability to fully understand the nature of the study and voluntarily provide written informed consent.
• Willingness to comply with all study procedures and demonstrate good compliance during the study period.
• Agreement to participate in long-term follow-up.

Exclusion Criteria:

• Patients with ARDS caused by COVID-19 infection.
• Patients currently suffering from hepatitis B, hepatitis C, active or latent tuberculosis, AIDS, syphilis, immunodeficiency disorders, or other immune system diseases.
• Presence of severe cardiovascular diseases at screening, including:Cardiac function classification of NYHA class III or higher.Uncontrolled myocarditis or valvular disease.Malignant arrhythmia requiring pharmacological treatment.
• Abnormal liver or renal function at screening meeting any of the following criteria:ALT or AST ≥ 5 × ULN, or total bilirubin ≥ 3 × ULN.Serum creatinine ≥ 3 × ULN, or patients currently undergoing renal replacement therapy (CRRT).
• Patients receiving extracorporeal membrane oxygenation (ECMO) therapy at the time of screening.
• Severe hematological abnormalities at screening, including: hemorrhagic manifestations, PTA ≤ 40% (or INR ≥ 2.0), severe anemia (Hb < 60 g/L), moderate or severe thrombocytopenia (PLT < 50 × 10^9/L), disseminated intravascular coagulation (DIC), leukemia, or other hematological abnormalities deemed ineligible for the study.
• Severe end-stage respiratory diseases at screening.
• Pulmonary hypertension with a pulmonary artery pressure > 70 mmHg.
• History of deep vein thrombosis or pulmonary embolism within the 6 months prior to enrollment.
• Patients post lung transplantation.
• Presence of severe cardiopulmonary malformations at screening.
• Severe psychiatric disorders.
• Patients who are pregnant (positive pregnancy test), breastfeeding, or have a pregnancy plan, are unwilling to practice contraception during the study and for 12 months after the infusion, or are of childbearing potential and unwilling to use effective contraception.
• Use of high-dose corticosteroids equivalent to methylprednisolone > 240 mg/day within 3 days prior to enrollment, or long-term irregular use of systemic corticosteroids for other diseases, which, in the investigator's judgment, may affect efficacy evaluation.
• Allergy to any component of the Human Umbilical Cord Mesenchymal Stem Cell Injection (e.g., human albumin), or a history of severe allergies deemed by the investigator as unsuitable for participation.
• Concurrent participation in another interventional clinical trial, or participation in another interventional clinical trial within the 3 months prior to screening.
• History or current diagnosis of malignancy, or pathological confirmation of precancerous lesions.
• Any other condition that, in the investigator's judgment, would lead to premature termination of the study, such as non-adherence to the protocol, concurrent severe illnesses requiring combined treatment, significant laboratory abnormalities, or social/family factors that could compromise the patient's safety or data collection.