Study of Therapeutic Efficacy of Anti-CD19 CAR-T Cell Therapy in Patients With MDR-SRNS

Study of Therapeutic Efficacy of Anti-CD19 Chimeric Antigen Receptor T Lymphocytes (CAR-T) Cells in Patients With Multi-drug Resistant SRNS

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-CD19 CAR-T cells in the treatment of patients with Multi-drug resistant SRNS

Study Overview

• Status: Recruiting
• Conditions: CAR-T Cell Therapy; Multi-Drug Resistant Nephrotic Syndrome
• Intervention / Treatment: Biological: anti-CD19 CAR-T cells

Detailed Description

At present, there is no effective treatment for Multi-drug resistant steroid resistant nephrotic syndrome (MDR-SRNS), which has a high risk of progression to kidney failure, and about 55% of patients will have disease recurrence after receiving kidney transplantation, which is in urgent need of new treatment methods.

CAR-T therapy is an adoptive cell therapy that uses genetic modification technology to reprogram T cells and eliminate target cells expressing disease-related antigens through antigen-specific recognition.Since 2019, CAR-T cell therapy has been successfully applied to autoimmune diseases. Although no clinical data related to CAR-T treatment of nephrotic syndrome has been disclosed, CAR-T is effective for systemic lupus erythematosus and systemic sclerosis.Many kinds of autoimmune diseases such as chemical syndrome and idiopathic inflammatory dermatomyositis have good therapeutic effect. These results suggest that the therapeutic effect of CAR T cells may not be limited to systemic lupus erythematosus, but may also play a role in several different B-cell-mediated and autoantibody-driven human autoimmune diseases, which is expected to bring breakthroughs in the treatment of MDR-SRNS.The purpose of this study is to assess the safety and efficacy of the anti-CD19 CAR-T cells in the treatment of patients with MDR-SRNS.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianhua Mao, PhD; Phone Number: 13516819071; Email: maojh88@zju.edu.cn
• Study Contact Backup: Name: Guoping Huang, MM; Phone Number: 13738196684; Email: 6510018@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Children's Hospital, Zhejiang University School of Medicine
      • Contact: Jianhua Mao, PhD; Phone Number: 13516819071; Email: maojh88@zju.edu.cn
      • Principal Investigator: Jianhua Mao, PhD
      • Contact: Email: maojh88@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥2 years old, gender unlimited;
• 2.Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes （KDIGO） Guidelines and have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission (at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus; Other hormone replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab); Or if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin inhibitor, if the researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks and the patient or guardian has fully informed consent;
• 3. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
• 4. The functions of important organs are basically normal: Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2# Liver function: Asparagus cochinchinensis transaseminase (AST) and Alanine Aminotransferase (ALT)≤3.0 upper limit of normal, Total Bilirubin (TBIL) in serum ≤2.0×upper limit of normal; Lung function: No serious lung lesions, SpO2≥92%;
• 5. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• 6. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• 7. Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

• 1. Received CAR T cell therapy or other gene-modified cell therapy previously;
• 2. Patients had a cerebrovascular accident or seizure, or other active central nervous system disease within 6 months;
• 3. Genetic tests have confirmed hereditary kidney disease;
• 4. Renal biopsy has been confirmed as immunoglobulin A nephropathy, idiopathic membranous nephropathy or membranoproliferative glomerulonephritis;
• 5. Renal replacement therapy has been or is being performed within 3 months prior to transfusion. (if acute kidney injury factors were considered, patients with chronic kidney disease were excluded, and the benefits outweighed the risks as determined by the investigator and with the full and informed consent of the patient or guardian could be considered for inclusion);
• 6. Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
• 7. Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs;
• 8. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;
• 9. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
• 10. Macrophage activation syndrome occurred within 1 month prior to screening;
• 11. Received live vaccine within 4 weeks before screening;
• 12. Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
• 13. Tested positive in Blood pregnancy test;
• 14. Patients who participated in other clinical study within 1 months prior to enrollment;
• 15. Any other conditions that the investigators deem it unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR-T treatment group; This study employs a '3+3' design with three dosage groups (0.3×10^5/kg, 1×10^5/kg, and 3×10^5/kg). Each dosage group will enroll 3 to 6 patients, starting from the lowest dosage and escalating to explore a safe and effective dose. Once a dosage group completes enrollment without observing any serious unexpected adverse reactions, and based on the efficacy and cell kinetics data, the investigator and the technical team together may consider escalating to the next dosage group to explore the optimal effective dose. The trial is expected to enroll a total of 9 to 18 patients

Biological: anti-CD19 CAR-T cells; Three dose groups (0.3×105/kg, 1×105/kg, 3×105/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of CAR-T cell therapy in patients with MDR SRNS	Incidence and severity of Adverse Events (AEs) and Serious Adverse Event（SAEs）,including changes in laboratory values,Electrocardiograph(ECG) and vital signs assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.	3 months
The efficiency of CAR-T cell therapy in patients with MDR SRNS	Complete response and partial response rate (complete response defined as Urinary protein/creatinine ratio (uPCR) ≤200 mg/g for 3 consecutive days, partial response is defined as a 50% or more reduction in proteinuria from baseline and 200mg/g < uPCR <2000mg/g)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of other visit points	Rate of complete or partial response at other visit points after cell infusion (1 month, 2 months, 6 months, 9 months, 12 months, 18 months, 24 months)	24 months
Pharmacokinetic Outcome Cmax	The highest concentration (Cmax) of targeted CD19 CAR-T cells expanded in peripheral blood after infusion	3 months
Pharmacokinetic Outcome Tmax	The time to reach the maximum concentration (Tmax)	3 months
Pharmacokinetic Outcome AUC	The area under the curve (AUC) at 28 days and 90 days post-infusion (AUC28d/90d)	3 months
Pharmacodynamics Outcome	The degree of B cell clearance at various time points, and the concentration levels of CAR-T related serum cytokines such as IL-6, CRP, etc	3 months

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2025
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Multi-Drug Resistant Nephrotic Syndrome; car-t
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: 2025-SC-0001-P-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No