Relapsed/Refractory Immune-mediated Kidney Disease, Relapsed/Refractory Immune Nephropathy
Conditions
Brief summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19/BCMA U CAR T cell injection (KN3601) in patients with Relapsed/Refractory immune-mediated kidney disease
Interventions
BIOLOGICALanti-CD19/BCMA U CAR T
To evaluate the safety and effectiveness of anti-CD19/BCMA CAR T cells (KN3601) in patients with immune nephropathy. All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by anti-CD19/BCMA U CAR T cells infusion.
Sponsors
Changhai Hospital
Rui Therapeutics Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age: ≥ 18 years old and ≤ 70 years old, male or female; 2. 2 B cell CD19 positive expression in peripheral blood detected by flow cytometry; 3. The functions of critical organs meet the following requirements: 1. Neutrophil count ≥ 1 x 10\^9/L, Hemoglobin ≥60g/L, platelets ≥ 50×109/L, 2. Liver function: ALT ≤ 3 x ULN,AST≤3 x ULN, TBIL≤1.5 x ULN, 3. Coagulation function: International standardized ratio (INR) ≤ 1.5x ULN, prothrombin time (PT) ≤1.5 x ULN, 4. Cardiac function: good hemodynamic stability, left ventricular ejection fraction (LVEF) ≥55%. 4. Female subjects of childbearing potential and male subjects whose partner is a female of childbearing potential are required to use medically approved contraception or abstain from sex for at least 6 months during and at least 6 months after the end of the study treatment period; female subjects of childbearing potential have had a negative serum HCG test within 7 days prior to study enrollment and are not lactating; 5. Voluntarily participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up. Specific inclusion criteria: High-risk or relapsed/refractory primary membranous nephropathy 6. Primary membranous nephropathy diagnosed pathologically by renal biopsy; 7. Meets the clinical criteria for high-risk or recurrent/refractory membranous nephropathy, defined as: Subjects at risk who meet any of the following criteria: a) estimated glomerular filtration rate (eGFR, CKD-EPI equation) \<60 mL/min/1.73m², and/or urine protein \>8g/day persisting for more than 6 months;b) normal GFR, urinary protein \>3.5 g/d, treated with ACEI/ARB for 6 months, urinary protein reduction \<50%, and serum albumin \<25 g/l or aPLA2R \>50 RU/mL; Refractory membranous nephropathy subjects are defined as those who have shown poor response or resistance to previous immunosuppressive treatments (including corticosteroids and/or cytotoxic drugs, immunosuppressants and/or biologics), defined as persistent proteinuria ≥3.5g/day with a reduction of \<50% compared to baseline; Recurrent membranous nephropathy is defined as a relapse (24-hour urinary protein ≥3.5 g) in subjects who have achieved complete or partial remission following treatment; 8. Subjects with relapsed/refractory MN and eGFR ≥ 45 mL/min/1.73 m2 during the screening period; 9. Primary IgA nephropathy pathologically confirmed by renal biopsy; 10. Subjects have medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening; 11. Subjects have been treated with hormones and/or cytotoxic drugs, immunosuppressants and/or biological agents (including but not limited to anti-CD20 monoclonal antibodies) for more than 6 months, and the 24-hour urine protein is ≥1.0 g; subjects with a rapidly progressive decline in kidney function (eGFR decreases by ≥50% within 3 months); or The subject relapsed after achieving complete remission/partial remission (CR/PR) following treatment (24-hour urine protein ≥1.0 g); 12. Estimated glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 mL/min/1.73m2 at screening; 13. Meets the 2022 ACR/EULAR diagnostic criteria for ANCA-associated vasculitis, including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis; 14. ANCA-related antibodies positive (MPO-ANCA or PR3-ANCA positive); 15. Kidney biopsy pathology is consistent with ANCA-associated vasculitis renal damage; 16. Birmingham Vasculitis Activity Score (BVAS) ≥15 points (total score 63 points), indicating active vasculitis; 17. At least two abnormalities related to the kidneys in the BVAS score; 18. Subjects meeting the definition of relapsed/refractory: standard treatment is ineffective or disease activity recurs after remission. Definition of conventional treatment: using glucocorticoids (more than 1mg/kg/day) and cyclophosphamide, along with any one of the following immunomodulatory drugs for ≥3 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including rituximab, belimumab, and thalidomide; 19. Estimated glomerular filtration rate (eGFR, CKD-EPI formula) ≥30 mL/min/1.73m2 at screening
Exclusion criteria
Subjects who meet any of the following common
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | up to 52 weeks after infusion | To characterize the safety of anti-CD19/BCMA U CAR T Cells (KN3601) for Relapsed/Refractory Immune Nephropathy |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | up to 52 weeks after infusion | To characterize the safety of anti-CD19/BCMA U CAR T Cells (KN3601) for Relapsed/Refractory Immune Nephropathy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The overall response rate (ORR) | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells for Relapsed/Refractory Immune Nephropathy |
| Disease control rate (DCR) | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells for Relapsed/Refractory Immune Nephropathy |
| B cell depletion rate | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells for Relapsed/Refractory Immune Nephropathy |
| B cell reconstitution | up to 52 weeks after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells for Relapsed/Refractory Immune Nephropathy |
Countries
China
Contacts
CONTACTZhiyong Guo, Dr
Outcome results
None listed