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

Official title

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

Overview

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.

Interventions

• Biological 1 vial containing a total of 5×10^7 cells
  venous reinfusion
• Biological 2 vial containing a total of 1×10^8 cells
  venous reinfusion
• Biological 3 vial containing a total of 1.5×10^8 cells
  venous reinfusion
• Biological 4 vial containing a total of 2×10^8 cells
  venous reinfusion

Primary outcome measures

• DLT incidence rate [Time frame: within 28 days after administration]
• Maximum Tolerated Dose [Time frame: Periprocedural]
• Any adverse events related to MSCs therapy [Time frame: within 28 days after administration]

Secondary outcome measures (11)

• Incidence of Clinically Significant Changes in Vital Signs from Baseline [Time frame: within 28 days after administration]
• Incidence of clinically significant changes in laboratory tests from baseline [Time frame: within 28 days after administration]
• male/female tumor marker positive rate [Time frame: within 28 days after administration]
• all-cause mortality [Time frame: within 28 days after administration]
• Time of non-mechanical ventilation (days) [Time frame: within 28 days after administration]
• Non-intensive care time (days) [Time frame: within 28 days after administration]
• Time without organ failure (days) [Time frame: within 28 days after administration]
• PaO2/FiO2 varies from baseline [Time frame: 24 hours, 3, 7, 14, 28 days after infusion of test drug]
• Arterial blood gas analysis (pH, PaO _ 2, PaCO _ 2, Lac) changed from baseline [Time frame: 24 hours, 3, 7, 14, 28 days after infusion of test drug]
• Lung injury score changes from baseline [Time frame: Days 7, 14, 28]
• Sequential organ failure score changes from baseline [Time frame: Days 3, 7, 14, 28]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongnan Hospital of Wuhan University — Wuhan

Identifiers

NCT: NCT07413978 · TH-MSC-ARDS-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗