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- Ensayo clínico NCT07706855
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Bin Du, M.D.
- Número de teléfono: +86-10-69151188
- Correo electrónico: dubin98@gmail.com
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Phase I: GKL-006RTU injection (1 or 3 Bags)
A single-arm, open-label dose-escalation study. Dose Level 1: 1 bag of GKL-006RTU injection (25 mL/bag, containing 5.0±0.5×10^8 iNKT cells). Dose Level 2: 3 bags of RTU injection (25 mL/bag, containing 5.0±0.5×10^8 iNKT cells per bag). Dose escalation follows the '3+3' design based on dose-limiting toxicities (DLTs) observed within a 28-day safety window. All participants will receive standard of care background therapy as per clinical guidelines, including restrictive fluid management and lung-protective ventilation strategies. Supportive care medications (for example, antibiotics, albumin, diuretics) and organ support will be administered at the investigator's discretion based on individual patient needs. |
iNKT cell injection
|
|
Experimental: Phase II: GKL-006RTU Injection
Participants in this arm will receive the Recommended Phase II Dose of GKL-006RTU injection . This is a randomized, double-blind portion of the study. All participants will receive standard of care background therapy as per clinical guidelines, including restrictive fluid management and lung-protective ventilation strategies. Supportive care medications (for example, antibiotics, albumin, diuretics) and organ support will be administered at the investigator's discretion based on individual patient needs. |
iNKT cell injection
|
|
Comparador de placebos: Phase II: Placebo
Participants in this arm will receive matching placebo. They will be randomized in a 1:1 ratio to the GKL-006RTU injection arm. The study is double-blind. All participants will receive standard of care background therapy as per clinical guidelines, including restrictive fluid management and lung-protective ventilation strategies. Supportive care medications (for example, antibiotics, albumin, diuretics) and organ support will be administered at the investigator's discretion based on individual patient needs. |
Matching placebo for GKL-006RTU injection
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase I: Incidence and Severity of Adverse Events and Serious Adverse Events
Periodo de tiempo: Day 1 to Day 180
|
To evaluate the safety and tolerability of GKL-006RTU injection in participants with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).
Safety will be assessed throughout the study duration, from Day 1 to Day 180.
|
Day 1 to Day 180
|
|
Phase II: Difference in Ventilator-Free Days within 28 Days Compared to Placebo
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the efficacy of GKL-006RTU injection compared to placebo in participants with moderate-to-severe ARDS.
The primary efficacy endpoint is the difference in ventilator-free days (days alive and free from mechanical ventilation) within 28 days post-treatment between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase I: All-cause Mortality at Day 1 to Day 28, Day 90, and Day 180
Periodo de tiempo: Day 1 to Day 28, Day 90, and Day 180
|
To assess the all-cause mortality rate in participants treated with GKL-006RTU injection at Day 1 to Day 28, Day 90, and Day 180.
|
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
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the number of days alive and free from mechanical ventilation, intensive care unit (ICU) stay, and organ support from Day 1 to Day 28.
|
Day 1 to Day 28
|
|
Phase I: Change in Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen Ratio (PaO2/FiO2) from Baseline
Periodo de tiempo: Day 1 to Day 28
|
The ratio is calculated by dividing the arterial partial pressure of oxygen by the fraction of inspired oxygen.
Measurements will be taken at baseline and various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
|
Phase I: Change in Arterial Potential of Hydrogen (pH) from Baseline
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the change in arterial pH from baseline at various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
|
Phase I: Change in Arterial Partial Pressure of Oxygen (PaO2) from Baseline
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the change in arterial partial pressure of oxygen (PaO2) from baseline at various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
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Phase I: Change in Arterial Partial Pressure of Carbon Dioxide (PaCO2) from Baseline.
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the change in arterial partial pressure of carbon dioxide (PaCO2) from baseline at various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
|
Phase I: Change in Arterial Lactate from Baseline
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the change in arterial lactate levels from baseline at various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
|
Phase I: Change in Sequential Organ Failure Assessment (SOFA)-2 Score from Baseline
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the change in the Sequential Organ Failure Assessment (SOFA)-2 score from baseline.
The SOFA-2 score ranges from 0 to 24, with higher scores indicating more severe organ dysfunction/failure.
Assessments will be made at various time points from Day 1 to Day 28.
|
Day 1 to Day 28
|
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Phase II: Difference in All-cause Mortality Compared to Placebo at Day 7, Day 14, Day 28, Day 90, and Day 180
Periodo de tiempo: Day 7, Day 14, Day 28, Day 90, and Day 180
|
To evaluate the difference in all-cause mortality between the GKL-006RTU injection group and the placebo group at Day 7, Day 14, Day 28, Day 90, and Day 180.
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Day 7, Day 14, Day 28, Day 90, and Day 180
|
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Phase II: Difference in ICU-Free Days and Organ Support-Free Days Compared to Placebo within Day 1 to Day 28
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in days free from intensive care unit (ICU) stay and days free from organ support between the GKL-006RTU injection group and the placebo group from Day 1 to Day 28.
|
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
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of the PaO2/FiO2 ratio from baseline between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
|
Phase II: Difference in Change of Arterial Potential of Hydrogen (pH) Compared to Placebo.
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of arterial pH from baseline between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
|
Phase II: Difference in Change of Arterial Partial Pressure of Oxygen (PaO2) Compared to Placebo.
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of arterial partial pressure of oxygen (PaO2) from baseline between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
|
Phase II: Difference in Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2) Compared to Placebo
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of arterial partial pressure of carbon dioxide (PaCO2) from baseline between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
|
Title: Phase II: Difference in Change of Arterial Lactate Compared to Placebo
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of arterial lactate levels from baseline between the GKL-006RTU injection group and the placebo group.
|
Day 1 to Day 28
|
|
Phase II: Difference in Change of Sequential Organ Failure Assessment (SOFA)-2 Score Compared to Placebo
Periodo de tiempo: Day 1 to Day 28
|
To evaluate the difference in the change of the Sequential Organ Failure Assessment (SOFA)-2 score from baseline between the GKL-006RTU injection group and the placebo group.
The SOFA-2 score ranges from 0 to 24, with higher scores indicating more severe organ dysfunction or failure.
|
Day 1 to Day 28
|
|
Phase II: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Periodo de tiempo: Day 1 to Day 180
|
Day 1 to Day 180
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
[Phase I & II] Immunogenicity Assessment: Anti-MHC Antibodies and Donor-Specific Antibodies (DSA)
Periodo de tiempo: Day 1, Day 14, Day 28, and Day 90
|
Detection of allogeneic antibodies against Major Histocompatibility Complex (MHC) Class I and Class II.
If positive, the Mean Fluorescence Intensity (MFI) of Donor-Specific Antibodies (DSA) will be measured.
This applies to both Phase I and Phase II cohorts.
|
Day 1, Day 14, Day 28, and Day 90
|
|
[Phase I & II] Pharmacokinetics (PK): Count of Allogeneic Invariant Natural Killer T (iNKT) Cells
Periodo de tiempo: Day 1 to Day 4, Day 7, Day 14, Day 28, and Day 90
|
Enumeration of allogeneic invariant natural killer T (iNKT) cells in peripheral blood post-treatment.
This assessment is conducted in both Phase I and Phase II.
|
Day 1 to Day 4, Day 7, Day 14, Day 28, and Day 90
|
|
[Phase I & II] Pharmacodynamics (PD): Inflammatory Cytokines and Acute Phase Reactants
Periodo de tiempo: Day 1, Day 4, Day 7, Day 14, Day 28, and Day 90
|
Measurement of changes in peripheral blood levels of: oC-reactive protein (CRP) oInterleukin-1 Receptor Antagonist (IL-1RA) oInterleukin-6 (IL-6) oInterleukin-8 (IL-8) oTumor Necrosis Factor-alpha (TNF-α) oInterferon-gamma (IFN-γ) Soluble Tumor Necrosis Factor Receptor 1 (sTNFr1) |
Day 1, Day 4, Day 7, Day 14, Day 28, and Day 90
|
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[Phase I & II] Pharmacodynamics (PD): Serum Bicarbonate (HCO3-) Levels
Periodo de tiempo: Day 1, Day 4, Day 7, Day 14, Day 28, and Day 90
|
Measurement of changes in serum bicarbonate (HCO3-) levels in peripheral blood post-treatment for both Phase I and Phase II cohorts.
|
Day 1, Day 4, Day 7, Day 14, Day 28, and Day 90
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GKL006RTUST01
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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