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

Official title

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

Overview

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.

Interventions

• Drug GKL-006RTU injection
  iNKT cell injection
• Drug Placebo
  Matching placebo for GKL-006RTU injection

Primary outcome measures

• Phase I: Incidence and Severity of Adverse Events and Serious Adverse Events [Time frame: Day 1 to Day 180]
• Phase II: Difference in Ventilator-Free Days within 28 Days Compared to Placebo [Time frame: Day 1 to Day 28]

Secondary outcome measures (12)

• Phase I: All-cause Mortality at Day 1 to Day 28, Day 90, and Day 180 [Time frame: Day 1 to Day 28, Day 90, and Day 180]
• Phase I: Ventilator-Free Days, ICU-Free Days, and Organ Support-Free Days within Day 1 to Day 28 [Time frame: Day 1 to Day 28]
• Phase I: Change in Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen Ratio (PaO2/FiO2) from Baseline [Time frame: Day 1 to Day 28]
• Phase I: Change in Arterial Potential of Hydrogen (pH) from Baseline [Time frame: Day 1 to Day 28]
• Phase I: Change in Arterial Partial Pressure of Oxygen (PaO2) from Baseline [Time frame: Day 1 to Day 28]
• Phase I: Change in Arterial Partial Pressure of Carbon Dioxide (PaCO2) from Baseline. [Time frame: Day 1 to Day 28]
• Phase I: Change in Arterial Lactate from Baseline [Time frame: Day 1 to Day 28]
• Phase I: Change in Sequential Organ Failure Assessment (SOFA)-2 Score from Baseline [Time frame: Day 1 to Day 28]
• Phase II: Difference in All-cause Mortality Compared to Placebo at Day 7, Day 14, Day 28, Day 90, and Day 180 [Time frame: Day 7, Day 14, Day 28, Day 90, and Day 180]
• Phase II: Difference in ICU-Free Days and Organ Support-Free Days Compared to Placebo within Day 1 to Day 28 [Time frame: Day 1 to Day 28]
• Phase II: Difference in Change of Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen Ratio (PaO2/FiO2) Compared to Placebo [Time frame: Day 1 to Day 28]
• Phase II: Difference in Change of Arterial Potential of Hydrogen (pH) Compared to Placebo. [Time frame: Day 1 to Day 28]

Eligibility criteria

Inclusion criteria

• Male or female, aged 18 to 80 years (inclusive).
• 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.
• Clinically diagnosed with Acute Respiratory Distress Syndrome (ARDS) according to the diagnostic criteria, with a time from diagnosis to enrollment not exceeding 96 hours.
• The etiology of ARDS is confirmed to be infectious.
• 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).
• 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

• 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).
• Known immune system dysfunction (e.g., primary immunodeficiency, acquired immunodeficiency) or currently receiving systemic immunosuppressive therapy.
• Expected survival time of less than 72 hours.
• 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.
• Currently receiving or expected to receive Extracorporeal Membrane Oxygenation (ECMO) during the trial period.
• 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 ).
• 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.
• Severe end-stage respiratory diseases at screening (e.g., COPD with respiratory failure, pulmonary fibrosis, pulmonary hypertension with right heart failure, etc., excluding ARDS).
• History of deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment.
• History of solid organ or hematopoietic stem cell transplantation.
• Severe cardiopulmonary malformations at screening that significantly affect cardiopulmonary function.
• Severe neuropsychiatric disorders (e.g., Alzheimer's disease, schizophrenia).
• ARDS caused by other etiologies (e.g., trauma, aspiration).
• Pregnant or lactating women.
• Cumulative corticosteroid use equivalent to > 400 mg of prednisone within 3 weeks prior to screening.
• Known hypersensitivity to any component of the investigational product, or a history of severe allergies deemed unsuitable for enrollment by the investigator.
• Receipt of cell therapy within 6 months prior to screening.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07706855 · GKL006RTUST01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗