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

NCT06842589 | Recruiting Phase 1

• 1 other identifier: 2025-SC-0001-P-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multi-Drug Resistant Nephrotic Syndrome; CAR-T Cell Therapy

Keywords

car-t; Multi-Drug Resistant Nephrotic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Effectiveness of other visit points

  24 months

• Pharmacokinetic Outcome Cmax

  3 months

• Pharmacokinetic Outcome Tmax

  3 months

• Pharmacokinetic Outcome AUC

  3 months

• Pharmacodynamics Outcome

  3 months

Study Arms (1)

CAR-T treatment group

EXPERIMENTAL

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

Interventions

anti-CD19 CAR-T cells BIOLOGICAL

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.

CAR-T treatment group

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥2 years old, gender unlimited;
• \. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
• \. 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%;
• \. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
• \. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
• \. 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.

You may not qualify if:

• \. Received CAR T cell therapy or other gene-modified cell therapy previously;
• \. Patients had a cerebrovascular accident or seizure, or other active central nervous system disease within 6 months;
• \. Genetic tests have confirmed hereditary kidney disease;
• \. Renal biopsy has been confirmed as immunoglobulin A nephropathy, idiopathic membranous nephropathy or membranoproliferative glomerulonephritis;
• \. Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
• \. 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;
• \. 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;
• \. 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;
• \. Macrophage activation syndrome occurred within 1 month prior to screening;
• \. Received live vaccine within 4 weeks before screening;
• \. Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
• \. Tested positive in Blood pregnancy test;
• \. Patients who participated in other clinical study within 1 months prior to enrollment;
• \. Any other conditions that the investigators deem it unsuitable for the study.

Sponsors & Collaborators

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

Study Sites (1)

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Nephrotic Syndrome

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Jianhua Mao, PhD

CONTACT

13516819071; maojh88@zju.edu.cn

Guoping Huang, MM

CONTACT

13738196684; 6510018@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 24, 2025
• Study Start: May 14, 2025
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: May 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)