The BCMA/CD19 Dual Targeted CAR-T Cell in Participants With Autoimmune Kidney Diseases

NCT06285279 | Recruiting Phase 1 DMC

• 1 other identifier: NJCT-2401
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, open-label, dose-escalation exploratory clinical trial, expected to enroll 6 to 12 participants. It will use a BOIN (Bayesian Optimal Interval) design for dose escalation, with four predetermined dose groups (0.3×10\^6 cells/kg, 1.0×10\^6 cells/kg, 3.0×10\^6 cells/kg, and an alternative dose of 0.1×10\^6 cells/kg). Each dose group plans to enroll 1-2 or 3-6 participants with relapsed or refractory autoimmune-mediated kidney diseases (such as lupus nephritis, ANCA-associated vasculitis, membranous nephropathy, and IgG4-related diseases).

Conditions

Lupus Nephritis; ANCA-associated Vasculitis; Membranous Nephropathy - PLA2R Induced; IgG4-Related Diseases

Outcome Measures

Primary Outcomes (2)

• The proportion of subjects with dose-limiting toxicity

  The number of participants with dose limiting toxicity in each dose group and the type of dose limiting toxicity that occurred.

  Within 28 days after the BCMA/CD19 dual targeted CAR-T cells injection infusion

• The proportion of subjects with adverse events

  All adverse events were evaluated according to NCI-CTCAE v5.0 criteria.

  Within 24 weeks after the BCMA/CD19 dual targeted CAR-T cells injection infusion

Secondary Outcomes (4)

• Proportion of subjects achieving renal response

  Within 6 months after the BCMA/CD19 dual targeted CAR-T cells injection infusion

• Duration of response (DoR) of all subjects

  Within 2 years after the BCMA/CD19 dual targeted CAR-T cells injection infusion

• Progression-free survival (PFS) of all subjects

  Within 2 years after the BCMA/CD19 dual targeted CAR-T cells injection infusion

• Overall survival (OS) of all subjects

  Within 2 years after the BCMA/CD19 dual targeted CAR-T cells injection infusion

Study Arms (1)

Treatment arm

EXPERIMENTAL

Administration of the BCMA/CD19 dual targeted CAR-T cells Four dose groups of 0.1×10\^6 CAR-T/kg, 0.3×10\^6 CAR-T/kg, 1.0×10\^6 CAR-T/kg, and 3.0×10\^6 CAR-T/kg FKC288 are designed in this study. Each dose group plans to enroll 1-2 or 3-6 participants with relapsed or refractory autoimmune-mediated kidney diseases (such as lupus nephritis, ANCA-associated vasculitis, membranous nephropathy, IgG4-related diseases) according to observed DLT. the BCMA/CD19 dual targeted CAR-T cells will be intravenously infused at least 24 hours after lymphodepletion preconditioning. According to the assigned dose group, the designated dose of the BCMA/CD19 dual targeted CAR-T cells will be infused in a single infusion within 30 minutes on day 0.

Drug: FKC288

Interventions

FKC288 DRUG

The autologous dual target BCMA/CD19-CAR-T cell of this study is obtained by infecting T cells with anti-BCMA/CD19-CAR lentiviral vectors. Administration method: intravenous infusion； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Participants must personally sign an informed consent form approved by the Ethics Committee before the start of the study.
• Participants must be aged ≥18 and ≤65 years.
• Active, relapsing, refractory Lupus Nephritis (LN):
• LN diagnosed by kidney biopsy within the last 2 years, with pathological types III, IV, or V, and a chronicity index (CI) score≤3
• Meets one of the following criteria:
• Refractory LN, defined as no remission after at least one standard regimen (CTX and/or MMF) for 6 months.
• Relapsing LN, defined as a need to increase steroid dosage to control disease activity during maintenance treatment.
• Clinical criteria: eGFR \> 45 ml/min/1.73 m²; urinary protein quantification ≥ 1.5g/24h; SLE-DAI score ≥ 8.
• ANCA-associated vasculitis (AAV) patients:
• Diagnosed as AAV according to the 2012 Chapel Hill Consensus Conference criteria, meeting one of the following:
• Newly diagnosed AAV with renal involvement:
• Renal involvement must meet both:
• Kidney biopsy showing pauci-immune necrotizing glomerulonephritis. Urinary red blood cells \>30/high power field.
• Relapsing or refractory AAV:
• Relapse: Defined as an increase in BVAS V3.0 score of ≥1 after remission, requiring adjustment of immunosuppressive treatment to regain remission.

You may not qualify if:

• Participants who have received the following previous treatments:
• Participants who have received gene therapy before enrollment. 1.2 Participants who have been injected with live vaccines within 4 weeks prior to enrollment.
• Participants who have received other investigational drug treatments within 12 weeks before apheresis.
• Participants with active malignancies within the past 5 years, except for tumors deemed curable and cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc.
• Participants who are positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with abnormal peripheral blood HBV DNA tests (defined as HBV DNA quantification above the lower limit of detection or above the normal reference range of the testing center, or qualitative HBV DNA test positive); positive for Hepatitis C virus (HCV) antibodies with positive peripheral blood HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis test RPR.
• Participants with uncontrolled active infections (except for \< Grade 2 CTCAE urinary reproductive system infections and upper respiratory infections).
• Participants with severe heart diseases, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association \[NYHA\] class ≥ III), severe arrhythmias.
• Participants with hypertension or diabetes that cannot be controlled with medication.
• Participants with unresolved toxic reactions from previous treatments to baseline or ≤ Grade 1 (according to NCI-CTCAE v5.0, except for alopecia and clinically insignificant lab abnormalities).
• Participants who have undergone major surgery within 2 weeks prior to enrollment or plan to have surgery during the waiting period for infusion or within 12 weeks after receiving study treatment (except for planned minor surgeries under local anesthesia).
• Participants with solid organ transplants.
• Pregnant or breastfeeding women.
• Participants with a history of central nervous system diseases (such as cerebral aneurysm, epilepsy, stroke, dementia, psychosis, etc.) or consciousness disorders.
• Participants with other unstable systemic diseases as judged by the researcher, including but not limited to severe diseases of the liver, kidneys, gastrointestinal tract, or metabolic diseases requiring medication.
• Participants are known to have life-threatening allergic reactions, hypersensitivity, or intolerance to FKC288 cellular products or their components.

Sponsors & Collaborators

• Nanjing University School of Medicine: lead

Study Sites (1)

Jinling Hospital

Nanjing, Jiangsu, 210016, China

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunoglobulin G4-Related Disease

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases

Study Officials

• Zhihong Liu

  Jinling Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xianghua Huang, MD

CONTACT

13770648824; hxhszb@163.com

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: Professor

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: February 29, 2024
• Study Start: March 4, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)