Safety and Efficacy Study of GKL-006RTU in Moderate to Severe Acute Respiratory Distress Syndrome (ARDS)

A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of GKL-006RTU Injection in Patients With Moderate to Severe Acute Respiratory Distress Syndrome

This is a Phase I/II, multicenter study designed to evaluate the safety, tolerability, and preliminary efficacy of GKL-006RTU injection in participants with moderate to severe Acute Respiratory Distress Syndrome (ARDS).

The study consists of two parts:

Phase I is a single-arm, open-label study. Eligible participants will receive a single intravenous infusion of GKL-006RTU injection (1 bag or 3 bags, containing approximately 5.0±0.5×10^8 invariant natural killer T (iNKT) cells per bag) in addition to standard background treatment. The primary objective of this phase is to assess the safety and tolerability of the investigational product.

Phase II is a randomized, double-blind, placebo-controlled study. Based on the results from Phase I, participants will receive GKL-006RTU injection or placebo via intravenous infusion, in addition to standard background treatment. The primary objective of this phase is to evaluate the efficacy of GKL-006RTU injection in treating moderate to severe ARDS.

Inclusion Criteria:

1. Male or female, aged 18 to 80 years (inclusive).
2. Participants (or their legally authorized representatives, if the participant is unable to provide informed consent) who fully understand the nature of the study, voluntarily sign the informed consent form, and are willing to comply with and complete all study procedures during the study period.
3. Clinically diagnosed with Acute Respiratory Distress Syndrome (ARDS) according to the diagnostic criteria, with a time from diagnosis to enrollment not exceeding 96 hours.
4. The etiology of ARDS is confirmed to be infectious.
5. Received active treatment (including anti-infective therapy and lung-protective ventilation strategies) for at least 24 hours; and arterial blood gas analysis results within 6 hours prior to enrollment support the diagnosis of moderate-to-severe ARDS (defined as Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen Ratio (PaO2/FiO2) ≤ 200 mmHg and Positive End-Expiratory Pressure [PEEP] ≥ 5 cmH2O).
6. Participants and their partners must have no plans for reproduction, sperm donation, or egg donation for at least 6 months after the last dose of study drug, and must voluntarily adopt effective contraceptive measures deemed appropriate by the investigator.

Exclusion Criteria:

1. Positive screening for infectious diseases meeting any of the following: a)Active Hepatitis B virus infection (defined as [positive Hepatitis B Surface Antigen (HBsAg) or positive Hepatitis B Core Antibody (HBcAb)] with Hepatitis B Virus DNA [HBV-DNA] above the upper limit of normal); b) Hepatitis C virus (HCV) infection (defined as positive HCV antibody with HCV-RNA above the upper limit of normal); c) Human Immunodeficiency Virus (HIV) infection (defined as positive HIV antibody); d) Syphilis infection (defined as positive Treponema pallidum antibody).
2. Known immune system dysfunction (e.g., primary immunodeficiency, acquired immunodeficiency) or currently receiving systemic immunosuppressive therapy.
3. Expected survival time of less than 72 hours.
4. Occurrence of a cerebrovascular or cardiovascular event (unstable angina, congestive heart failure, myocardial infarction, or stroke) within the past 6 months; or severe cardiovascular disease at screening: New York Heart Association (NYHA) Functional Classification Class III or higher; uncontrolled myocarditis or valvular disease; hemodynamic instability, severe cardiac dysfunction, malignant arrhythmias, or severe rhythm/conduction abnormalities requiring drug therapy within the past 6 months.
5. Currently receiving or expected to receive Extracorporeal Membrane Oxygenation (ECMO) during the trial period.
6. Severe hepatic or renal dysfunction at screening: long-term hemodialysis and known severe renal impairment with an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m² (calculation method detailed in Appendix 6), currently requiring Continuous Renal Replacement Therapy (CRRT); or moderate to severe liver failure (Child-Pugh score > 12 ).
7. Severe hematological abnormalities at screening: evidence of bleeding with an International Normalized Ratio (INR) ≥ 2.0; severe anemia (Hemoglobin [Hb] < 60 g/L); moderate or greater thrombocytopenia (Platelets [PLT] < 50×10⁹/L); Disseminated Intravascular Coagulation (DIC); leukemia; or other hematological abnormalities deemed unsuitable for enrollment.
8. Severe end-stage respiratory diseases at screening (e.g., COPD with respiratory failure, pulmonary fibrosis, pulmonary hypertension with right heart failure, etc., excluding ARDS).
9. History of deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment.
10. History of solid organ or hematopoietic stem cell transplantation.
11. Severe cardiopulmonary malformations at screening that significantly affect cardiopulmonary function.
12. Severe neuropsychiatric disorders (e.g., Alzheimer's disease, schizophrenia).
13. ARDS caused by other etiologies (e.g., trauma, aspiration).
14. Pregnant or lactating women.
15. Cumulative corticosteroid use equivalent to > 400 mg of prednisone within 3 weeks prior to screening.
16. Known hypersensitivity to any component of the investigational product, or a history of severe allergies deemed unsuitable for enrollment by the investigator.
17. Receipt of cell therapy within 6 months prior to screening.