This is an investigator initiated, single-arm, open-label, dose-escalation study to explore the preliminary efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the universal STAR-T cell injection which is a CD19 and BCMA bispecific CAR-T cells in patients with autoimmune kidney diseases. Approximately 10-24 adult participants diagnosed as IgA nephropathy and primary membranous nephropathy will be enrolled. Three dose levels (1.5 E6 STAR-T cells/kg, 3.0 E6 STAR-T cells/kg and 4.5 E6 STAR-T cells/kg) will be established in this study, and the universal STAR-T cell will be administered as a single intravenous infusion. A recommended dose will be selected for subsequent dose-expansion studies to evaluate the safety and efficacy of universal STAR-T cell injection in participants with autoimmune kidney diseases based on the safety, PK results, and preliminary efficacy data. This study includes the screening period (D-28 to D-6), pre-clearance treatment and observation period (D-5 to D-1), cell infusion and main study endpoint observation period (D0 to W12 after infusion), and extended follow-up period (W12 to W104).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
There are three dose levels of STAR-T cells injection(1.5 E6 STAR-T cells/kg, 3.0 E6 STAR-T cells/kg and 4.5 E6 STAR-T cells/kg) .
Guangdong Provincial People's Hospital.
Guangdong, Guangzhou, China
Type, severity, and frequency of adverse events (AEs)
Characterization of treatment-emergent adverse events (TEAEs) graded by NCI-CTCAE v6.0, including laboratory abnormalities, vital sign changes, and infusion-related reactions.
Time frame: AEs will be observed until 24 weeks after STAR-T cells injection and extended to 104 weeks.
Incidence of Dose-Limiting Toxicities (DLTs).
To assess the safety and tolerability of STAR-T cells and determine the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D). DLTs are defined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v6.0.
Time frame: Within 28 days after START-T cells infusion.
Remission rates of IgAN at the week 12 and week 24
Remission include complete remission (CR) or partial remission (PR). (1) Complete remission (CR) is defined as 24-hour urine protein \< 0.5 g, or a 24-hour urine protein-to-creatinine ratio (UPCR) \< 0.5 g/g, accompanied by stable renal function which is defined as a decline in estimated glomerular filtration rate (eGFR) of ≤ 15% from baseline. (2) Partial remission (PR) is defined as 24-hour urine protein or 24-hour UPCR not meeting the CR criteria, but demonstrating a reduction of ≥ 50% from baseline.
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Remission rates of PMN at the week 12 and week 24
Remission include complete remission (CR) or partial remission (PR). (1) Complete remission (CR) is defined as 24-hour urine protein \< 0.5 g, or a 24-hour urine protein-to-creatinine ratio (UPCR) \< 0.5 g/g, accompanied by stable serum creatinine (defined as a fluctuation of ≤ 15% from baseline), and a serum albumin (ALB) level \> 3.5 g/dL (or 35 g/L). (2) Partial remission (PR) is defined as 24-hour urine protein maintained within the range of 0.5-3.5 g, or 24-hour UPCR maintained within the range of 0.5-3.5 g/g, accompanied by a reduction of ≥ 50% from baseline
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Changes in 24-hour UPCR from baseline in IgAN and PMN participants
24-hour urine sample will be collected and UPCR will be measured.
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Changes in 24-hour urinary protein excretion from baseline in IgAN and PMN participants
24-hour urine sample will be collected and urinary protein excretion will be measured.
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Changes in kidney function from baseline in IgAN and PMN participants
eGFR will be measured to evaluate kidney fucntion
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Changes in serum biomarkers from baseline in IgAN participants
Biomarkers include serum albumin, Gd-IgA1, C3, C4 and Immunoglobulins.
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Changes in serum biomarkers from baseline in PMN participants
Biomarkers include serum albumin, anti-PLA2R, C3, C4 and Immunoglobulins.
Time frame: From enrollment to the end of treatment at 12 weeks and 24 weeks, respectively
Maximum Plasma Concentration of Universal STAR-T Cells (Cmax)
To evaluate the maximum observed plasma concentration of Universal STAR-T Cells
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
Time to Reach Maximum Plasma Concentration (Tmax) of Universal STAR-T Cells.
To evaluate the time to reach the maximum observed plasma concentration of Universal STAR-T Cells.
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
Area Under the Plasma Concentration-Time Curve (AUC) of Universal STAR-T Cells
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To evaluate the total systemic exposure to Universal STAR-T Cells over time.
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
Change in PD Biomarkers
PD Biomarkers include serum serum cytokine concentrations, such as IL-1β, IL-2、IL-6, IL-8, TNF-α, and IFN-γ, using validated ELISA kits
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
Changes in B cells in peripheral blood
Evaluation of PD effects of Universal STAR-T Cells via serial quantification of CD19-positive B cells in peripheral blood, expressed as cells per microliter (cells/μL). Measurement will be performed using flow cytometry according to standardized laboratory protocols
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks
Change in plasma cells in peripheral blood
Evaluation of PD effects of Universal STAR-T Cells via serial quantification of plasma cells in peripheral blood, expressed as cells per microliter (cells/μL). Measurement will be performed using flow cytometry according to standardized laboratory protocols.T
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.
Anti-Drug Antibodies (ADA) against universal STAR-T cells
To evaluate the development of anti-drug antibodies (ADA) against allogeneic universal STAR-T cells in peripheral blood
Time frame: Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks