NCT07022197

Safety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Tianjin Medical University General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This study is a phase Ib/IIa dose-escalation study designed to evaluate the safety, tolerability, and preliminary efficacy of autologous T cells expressing chimeric antigen receptor (CAR)-targeted B-cell activating factor receptor (BAFFR) in refractory neuroimmune diseases. The study design is divided into two parts, the first of which will be given to each patient at 3 incremental dose levels to establish the maximum tolerated dose (MTD). Each disease is expected to enroll 12 patients who meet the inclusion criteria. In the second part, 15 patients per disease will be recruited to further characterize the efficacy of the MTD.

Detailed description

* Phase I: Frequency, type, and severity of adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events CTCAE V5.0) occurring within 4 weeks after BAFF-R CART infusion; * Phase II: Number of recurrences at 52 weeks after BAFF-R CART infusion; * Characterization of BAFF-R CART cell expansion levels over time in subjects (peripheral blood, cerebrospinal fluid, bone marrow, etc.); * Characteristics of BAFF-R+ B cell and antibody secreting cell (ASC) lymphocyte ablation in subjects; * Changes in disease-related clinical scores at baseline, 24 and 52 weeks after BAFF-R CART infusion; * Changes in the cumulative total number of MRI active lesions in MS and NMOSD patients at 24 and 52 weeks after BAFF-R CART infusion; * Frequency, type, and severity of treatment-related laboratory index abnormalities (according to the National Cancer Institute Common Terminology Criteria for Adverse Events CTCAE V5.0); * Characterization of changes in disease-associated antibody titers in the subject; * Changes in vital signs (blood pressure, pulse rate, weight, ECG).

Conditions

• Chronic Inflammatory Demyelinating Polyradiculoneuropathy
• NMO Spectrum Disorder
• Myasthenia Gravis
• Idiopathic Inflammatory Myopathies

Interventions

Type	Name	Description
DRUG	BAFF-R CART	Biological: BAFF-R CART cells Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to manufacture BAFF-R CART cells, during which cyclophosphamide will be administered for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with BAFF-R CART cells by intravenous (IV) infusion. The initial dose of 0.5×10\^6 CART cells/kg will be infused on day 0. Drug: Cyclophosphamide and fludarabine Subjects will receive one 3-day cycle of lymphodepletion starting 4 days prior to BAFF-R CART cells infusion on Day 0. Subjects will be given IV infusion of cyclophosphamide 250 mg/m2/day on day -5, -4 and -3, and fludarabine 30 mg/m2 over 30 minutes administered immediately after cyclophosphamide.

Timeline

• Start date: 2025-04-10
• Primary completion: 2027-12-30
• Completion: 2027-12-30
• First posted: 2025-06-15
• Last updated: 2025-06-15

Locations

1 site across 1 country: China