Safety and Efficacy of CD19 Chimeric Antigen Receptor T-Cell (CAR-T) in the Treatment of Refractory Membranous Nephropathy

NCT07266181 | Recruiting Phase 1 DMC

• 1 other identifier: KY20252388-F-1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, prospective, exploratory Phase I clinical trial initiated by the team led by Associate Professor He Lijie from the Department of Nephrology, Xijing Hospital. Prior to receiving CAR-T cell therapy, patients will undergo lymphodepletion chemotherapy with cyclophosphamide (fludarabine will be added if necessary). After prophylactic administration of antihistamines and acetaminophen, patients will be infused with CD19 CAR-T cells at a dose of 1×10⁶ cells/kg. In the subsequent 2 weeks, patients will be hospitalized for monitoring of vital signs and adverse reactions. The planned follow-up duration of this study is 1 years.

Conditions

Refractory Membranous Nephropathy

Outcome Measures

Primary Outcomes (2)

• Incidence of DLT in rMN subjects after a single infusion of CD19 CAR-T cells

  Definition: The DLT evaluated in this study is assessed within two time windows: 28 days (Day 0 to Day 28) and 3 months (Day 28 to Month 3) after CAR-T cell infusion. These time windows are selected based on the typical timeline of CAR-T cell expansion, activity, and potential occurrence of major toxicities in vivo. The determination of DLT must meet all the following criteria:1.DLT must be an adverse event judged by the investigator as probably or definitely related to CAR-T cell infusion, and cannot be attributed to underlying diseases, comorbidities, or toxicities from concomitant medications;2.The adverse event must reach a severity grade of ≥ Grade 3 (per CTCAE v5.0) or ≥ Grade 3 specific toxicity grading criteria (e.g., IEC-HS grading).

  28 days and 3 months after infusion

• Incidence of AE in rMN subjects after a single infusion of CD19 CAR-T cells

  Severity grading is based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: Mild; asymptomatic or mild symptoms; only clinically or diagnostically detectable; no treatment required. Grade 2: Moderate; requires minor, local, or non-invasive treatment; limitation in age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; results in hospitalization or prolongation of existing hospitalization; disabling; limitation in self-care activities of daily living. Grade 4: Life-threatening; requires urgent treatment. Grade 5: Death related to complications.

  12 months after infusion

Secondary Outcomes (18)

• Overall response rate (CR+PR) in rMN subjects after cell infusion

  Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion

• Proportion of rMN subjects achieving CR after cell infusion

  Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion

• Proportion of rMN subjects achieving PR after cell infusion

  Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion

• rMN recurrence after cell infusion

  Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion

• eGFR

  Week 2, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 18 (if applicable), Month 24 (if applicable) after infusion

Study Arms (1)

To preliminarily evaluate the safety and efficacy of CD19 CAR-T in refractory membranous nephropathy

OTHER

Other: All patients will receive CD19 CAR-T cell therapy on the basis of standard symptomatic and supportive treatment.

Interventions

All patients will receive CD19 CAR-T cell therapy on the basis of standard symptomatic and supportive treatment. OTHER

Prior to receiving CAR-T cell therapy, patients will undergo lymphodepletion chemotherapy with cyclophosphamide (fludarabine will be added if necessary). After prophylactic administration of antihistamines and acetaminophen, patients will be infused with CD19 CAR-T cells at a dose of 1×10⁶ cells/kg.

To preliminarily evaluate the safety and efficacy of CD19 CAR-T in refractory membranous nephropathy

Eligibility Criteria

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

You may qualify if:

• Confirmed as primary membranous nephropathy (PMN) by renal biopsy.
• Classified as moderate-risk or high-risk refractory membranous nephropathy (rMN).
• Moderate-risk rMN is defined as: eGFR ≥ 90 ml/min/1.73m² AND 24-hour urinary protein \> 3.5g/d, with a reduction of no more than 50% within 6 months of receiving renin-angiotensin system inhibitor (RASi) therapy.
• High-risk rMN is defined as meeting one of the following:
• eGFR \< 60 ml/min/1.73m² and/or persistent proteinuria \> 8g/d for more than 6 months.
• Normal eGFR with proteinuria \> 3.5g/d and ≤50% reduction after 6 months of RASi therapy, PLUS at least one of the following: Serum albumin \< 25g/L; PLA2R antibody \> 50 RU/mL; Urinary α1-microglobulin \> 40 μg/min; Urinary IgG \> 1 μg/min; Urinary β2-microglobulin \> 250 mg/d; IgG/albumin clearance ratio \> 0.20.
• Diagnosis of rMN requires failure of adequate first-line immunosuppressive therapy (≥6 months of steroids+cyclophosphamide, CNI, or rituximab), defined by any of the following: persistent high-titer anti-PLA2R antibody; for antibody-negative patients, persistent nephrotic syndrome (protein \>3.5g/d, albumin \<30g/L); \<50% reduction in proteinuria.
• Age ≥ 18 years.
• Adequate organ function, defined as:
• Renal: eGFR ≥ 30 ml/min/1.73m².
• Hepatic: ALT and AST ≤ 2.5 x ULN; Total bilirubin ≤ 1.5 x ULN.
• Cardiac: LVEF ≥ 50%; NYHA Class I or II; No significant arrhythmias requiring intervention; No major cardiovascular events within the past 6 months.
• Respiratory: SpO2 \> 92% on room air.
• Ability to understand and willingness to sign an Informed Consent Form.

You may not qualify if:

• Secondary membranous nephropathy (e.g., due to SLE, malignancy, drugs, infection).
• Active infection requiring IV antibiotics, active tuberculosis, or positive viral serology indicating active infection, including:
• HBV: HBsAg (+) and/or HBcAb (+) with detectable HBV DNA.
• HCV: HCV Ab (+) with detectable HCV RNA.
• HIV Ab (+).
• Active EBV or CMV infection (IgM+ or DNA above normal).
• Positive syphilis (Treponema pallidum) antibody (requires evaluation for active infection).
• Severe uncontrolled comorbidities, including:
• Uncontrolled hypertension (persistent SBP \> 160 mmHg or DBP \> 100 mmHg).
• Uncontrolled diabetes (HbA1c \> 8% or random glucose ≥11.1 mmol/L) or diabetic nephropathy.
• Symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months.
• Active peptic ulcer or gastrointestinal bleeding within the past 6 months.
• Severe congenital or acquired immunodeficiency.
• Severe CNS diseases (e.g., catastrophic APS, uncontrolled epilepsy).
• End-stage organ failure not attributable to PMN.

Sponsors & Collaborators

• The First Affiliated Hospital of Air Force Medicial University: lead

Study Sites (1)

Department of Nephrology, Xijing Hospital

Xi'an, China, 710012, China

RECRUITING

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Jipeng Li

CONTACT

8684775197; shaona@ldy.edu.rs

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: Research associate

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 5, 2025
• Study Start: December 8, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: December 24, 2025

Record last verified: 2025-08

Locations

CN (1)