Refractory Idiopathic Membranous Nephropathy
Conditions
Brief summary
A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19/BCMA Universal Chimeric Antigen Receptor T Cells (UCAR-T) in the Treatment of Refractory Idiopathic Membranous Nephropathy (IMN)
Interventions
DRUGCD19/BCMA-Targeted Universal Chimeric Antigen Receptor T Cells (UCAR-T) infusing
Patients will receive Fludarabine and Cyclophosphamide on day-5, -4, and -3. Single dose of CD19/BCMA-Targeted Universal Chimeric Antigen Receptor T Cells (KN3601) will infused using dose-escalation strategy.
Sponsors
The First Affiliated Hospital of Zhejiang Chinese Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 75 years inclusive, either gender; 2. Adequate function of major organs as defined below: 1. Absolute neutrophil count ≥ 1.0 × 10⁹/L, hemoglobin ≥ 60 g/L, platelet count ≥ 50 × 10⁹/L; 2. Hepatic function: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; total bilirubin (TBIL) ≤ 1.5 × ULN; 3. Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN; 4. Cardiac function: hemodynamically stable, left ventricular ejection fraction (LVEF) ≥ 50%; 3. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must use a medically acceptable contraceptive method or practice abstinence during study treatment and for at least 6 months after the end of treatment.Female subjects of childbearing potential must have a negative serum HCG test within 7 days prior to enrollment and must not be breastfeeding; 4. Voluntarily agree to participate in this clinical study, provide written informed consent, demonstrate good compliance, and be willing to comply with follow-up procedures; 5. Diagnosis of primary membranous nephropathy confirmed by renal biopsy pathology; 6. Meet the clinical criteria for high-risk or relapsed/refractory membranous nephropathy, defined as: High-risk patients meeting any of the following: 1. Estimated glomerular filtration rate (eGFR, CKD-EPI equation) \< 60 mL/min/1.73 m², and/or urinary protein \> 8 g/day for ≥ 6 months; 2. Normal eGFR, urinary protein \> 3.5 g/day despite ACEI/ARB treatment for 6 months with \< 50% reduction in proteinuria, plus serum albumin \< 25 g/L or anti-PLA2R antibody (aPLA2R) \> 50 RU/mL; Refractory membranous nephropathy: inadequate response or resistance to prior immunosuppressive therapy (including corticosteroids and/or cytotoxic agents, immunosuppressants and/or biologics), defined as persistent urinary protein ≥ 3.5 g/day with \< 50% reduction from baseline; Relapsed membranous nephropathy: recurrence (24-hour urinary protein ≥ 3.5 g) after achieving complete or partial remission (CR/PR) following treatment; 7. For relapsed/refractory membranous nephropathy patients during screening: eGFR ≥ 45 mL/min/1.73 m².
Exclusion criteria
1. Subjects with known allergic reaction, hypersensitivity, intolerance, or contraindication to CD19/BCMA universal CAR-T or any components of the study drugs (including fludarabine, cyclophosphamide, and tocilizumab), or a history of severe allergic reaction in the past. 2. Presence or suspicion of uncontrolled or treatable fungal, bacterial, viral, or other infections. 3. Central nervous system diseases caused by autoimmune or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis). 4. Subjects with severe cardiac diseases, such as angina pectoris, myocardial infarction, heart failure, arrhythmia, etc. 5. Subjects with congenital immunoglobulin deficiency. 6. Subjects with other malignant tumors (excluding non-melanoma skin cancer and carcinoma in situ of the cervix, bladder, or breast with disease-free survival \> 5 years). 7. Subjects with end-stage renal failure. 8. Subjects positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA titer above the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and HCV RNA; subjects positive for human immunodeficiency virus (HIV) antibody; subjects with positive syphilis test. 9. Subjects with psychiatric disorders and severe cognitive impairment. 10. Subjects who participated in other clinical trials within 6 months prior to enrollment. 11. Pregnant or lactating females, or females intending to become pregnant during the study. 12. Subjects with hypertension or diabetes mellitus that cannot be controlled by medication. 13. Subjects for whom the investigator considers there are other reasons for ineligibility. 14. Secondary membranous nephropathy (e.g., associated with hepatitis B, systemic lupus erythematosus, drug-related, malignancy-related, etc.), or concurrent renal disease confirmed by renal biopsy. 15. Type 1 or type 2 diabetes mellitus.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | up to 24 months after infusion | To characterize the safety of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Refractory Idiopathic Membranous Nephropathy |
| The overall response rate (ORR) | up to 24 months after infusion | To characterize the efficacy of anti-CD19/BCMA U CAR T Cells (KN3601) for patients with Refractory Idiopathic Membranous Nephropathy |
Countries
China
Contacts
CONTACTQiang He
Outcome results
None listed