A Clinical Study Evaluating the Safety and Efficacy of GT719 Universal Cell Injection in the Treatment of Immune-mediated Kidney Diseases
Overview
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- Grit Biotechnology
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability: Evaluate the incidence, correlation with the investigational product, severity, and other relevant aspects of adverse events (AEs) and serious adverse events (SAEs) occurring in participants during the trial
Overview
Brief Summary
This study is a single-arm, open-label, dose-escalation and dose-expansion clinical trial, divided into two phases: the first phase is the dose-escalation phase, and the second phase is the dose-expansion phase. In the dose-escalation phase, approximately 9-18 adult participants with immune-mediated kidney diseases are planned to be enrolled and treated with GT719 universal cell injection. The objectives of this phase are to evaluate the safety and tolerability of the product, determine the recommended dose (RD) for subsequent studies, conduct a preliminary assessment of its clinical efficacy, and investigate the pharmacokinetic and pharmacodynamic characteristics. Upon completion of the dose-escalation phase, after evaluation by investigators and collaborators, an appropriate dose will be selected for the dose-expansion phase. An additional 12 participants will be enrolled to fully assess the safety and efficacy of the product.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1\. The participant or their legal representative voluntarily signs a written informed consent form, and is willing and able to comply with the procedures of this study.
- •2\. Aged 18 to 75 years (inclusive) at the time of signing the informed consent, regardless of gender.
- •3\. Positive expression of CD19 on B cells in peripheral blood is confirmed by flow cytometry.
- •4\. Participants with IgA nephropathy (IgAN) at high risk of progression:
- •① A definite pathological diagnosis of IgAN confirmed by renal biopsy (renal biopsy must be performed within 2 years prior to screening or during the screening period).
- •Meet at least one of the following requirements:
- •Prior treatment with glucocorticoids, budesonide enteric-coated capsules, immunosuppressants (including mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus, Tripterygium wilfordii, leflunomide, azathioprine), or biological agents (including but not limited to anti-CD20 monoclonal antibodies, telitacicept, daratumumab) for a cumulative duration of at least 3 months, with persistent 24-hour urinary protein ≥ 0.75 g or UPCR ≥ 0.75 g/g.
- •The predicted probability of a 50% decline in eGFR or end-stage renal disease (ESRD) within 5 years calculated by the international IgAN prediction tool is ≥ 20%.
- •A ≥ 20% decline in eGFR within 3 months.
- •Renal biopsy performed within 6 months indicating Oxford classification C2 lesion.
Exclusion Criteria
- •1\. Participants with IgA nephropathy (IgAN) at high risk of progression:
- •a. Secondary IgAN (e.g., associated with active hepatitis B/hepatitis C infection, HIV, etc.).
- •2\. Participants with ANCA-associated vasculitis (AAV)/ANCA-associated glomerulonephritis (AAGN):
- •Drug-induced or secondary AAV/AAGN.
- •Alveolar hemorrhage requiring invasive mechanical ventilation support at screening.
- •3\. Participants with membranous nephropathy (MN):
- •a. Secondary membranous nephropathy.
- •4\. Participants with refractory podocytopathy:
- •a. Hereditary podocytopathy and secondary focal segmental glomerulosclerosis (FSGS).
- •5\. Participants with proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID):
Arms & Interventions
GT719 Injection treatment group
GT719 Injection
Intervention: CD19-targeted iNKT Cell Injection (Biological)
Outcomes
Primary Outcomes
Safety and Tolerability: Evaluate the incidence, correlation with the investigational product, severity, and other relevant aspects of adverse events (AEs) and serious adverse events (SAEs) occurring in participants during the trial
Time Frame: 24 Months
Based on the current version of the Common Terminology Criteria for Adverse Events (CTCAE) developed by the National Cancer Institute (NCI) of the United States, a systematic assessment of the safety and tolerability of the study subjects was conducted throughout the entire trial period.
Changes in vital signs before and after treatment
Time Frame: 1 Month
Dynamic monitoring of changes in vital signs before and after treatment, including heart rate, body temperature, blood pressure, etc.
Changes in clinical symptoms before and after treatment
Time Frame: 1 Month
A comparative analysis of the dynamic changes in clinical symptoms before and after treatment, including skin changes, pulmonary conditions, etc., is planned to be conducted.
Changes in laboratory tests before and after treatment
Time Frame: 1 Month
A comparative analysis of the dynamic changes in laboratory test indicators, including blood routine, blood biochemistry, relevant antibodies, etc., is planned to be conducted.
Changes in electrocardiograms before and after treatment
Time Frame: 1 Month
A comparative analysis of the dynamic changes in electrocardiograms is planned to be conducted.
Secondary Outcomes
- All Participants: Time to Maximum Expansion of Infused Cells (Tmax)(24 Months)
- All Participants: Peak Expansion Level of Infused Cells (Cmax)(24 Months)
- All Participants: Area Under the Curve of Infused Cells (AUC)(24 Months)
- All Participants: Duration of Observable Concentration (Tlast)(24 Months)
- All Participants: CAR-T-associated Serum Cytokines(2 Months)
- All Participants: CAR Cell Phenotype(24 Months)
- Participants with IgA nephropathy at high risk of progression：The proportion of participants who achieved complete response and partial response at 28 days, as well as at Months 2, 3, 6 and 12.(Day 28, Month 2, 3, 6 and 12)
- Participants with IgA nephropathy at high risk of progression： The estimated glomerular filtration rate (eGFR) slope at Day 14, Day 28, Month 2, Month 3, Month 6, and Month 12(Day 14 and 28, Month 2, 3, 6, and 12)
- Participants with ANCA-Associated Vasculitis (AAV)/ANCA-Associated Glomerulonephritis (AAGN): The proportion of participants who achieved complete response (CR) and partial response (PR) at 28 days, as well as at Months 2, 3, 6, and 12(Day 28, Month 2, 3, 6 and 12)
- Participants with ANCA-Associated Vasculitis (AAV)/ANCA-Associated Glomerulonephritis (AAGN): Changes in ANCA-MPO or PR3 antibody levels relative to baseline at Day 14, Day 28, as well as at Months 2, 3, 6, and 12(Day 14 and 28, Month 2, 3, 6, and 12)
- Participants with ANCA-Associated Vasculitis (AAV)/ANCA-Associated Glomerulonephritis (AAGN): Changes in Birmingham Vasculitis Activity Score (BVAS) relative to baseline at 28 days, as well as at Months 2, 3, and 6(Day 28, Month 2, 3 and 6)
- Participants with Membranous Nephropathy (MN): The proportion of participants who achieved complete response (CR) and partial response (PR) at 28 days, as well as at Months 2, 3, 6, and 12(Day 28, Month 2, 3, 6 and 12)
- Participants with Membranous Nephropathy (MN) : Changes in anti-PLA₂R antibody levels relative to baseline at Day 14, Day 28, as well as at Months 2, 3, 6, and 12(Day 14 and 28, Month 2, 3, 6, and 12)
- Participants with refractory podocytopathy: The proportion of participants who achieved complete response (CR) and partial response (PR) at 28 days, as well as at Months 2, 3, 6, and 12(Day 28, Month 2, 3, 6 and 12)
- Participants with refractory podocytopathy: The recurrence rate of nephrotic syndrome within 12 months(12 Months)
- Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits (PGNMID): The proportion of participants who achieved complete response (CR) and partial response (PR) at 28 days, as well as at Months 2, 3, 6, and 12(Day 28, Month 2, 3, 6 and 12)
- PGNMID: The proportion of participants with normalization of serum free light chain ratio (for those with abnormal baseline levels), and the negative rate of serum/urine immunofixation electrophoresis at Day 14, Day 28, as well as at Months 2, 3, 6, 12(Day 14 and 28, Month 2, 3, 6, and 12)