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

NCT07022197 | Recruiting Phase 1 DMC

• 1 other identifier: IRB2024-YX-274-01
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Types and incidence of dose-limiting toxicity (DLT) after BAFF-R CART cells infusion

  To evaluate the DLT occurred within 3 months after BAFF-R CART cells infusion.

  Up to 3 months post BAFF-R CART cells infusion

• Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms.

  To evaluate the AEs occurred within 2 years after BAFF-R CART cells infusion.

  Up to 2 years post BAFF-R CART cells infusion

Secondary Outcomes (5)

• PD-Soluble BAFF

  Up to 2 years post BAFF-R CART cells infusion

• PD-Pathogenic antibody

  Up to 2 years post BAFF-R CART cells infusion

• PD-Nfl（MS）

  Up to 2 years post BAFF-R CART cells infusion

• PK-VCN

  Up to 15 years post BAFF-R CART cells infusion

• PK-BAFF-R CAR-T cells

  Up to 2 years post BAFF-R CART cells infusion

Other Outcomes (31)

• NMOSD: the number of attacks

  Up to 2 years post BAFF-R CART cells infusion

• NMOSD: Accumulated total active MRI lesions

  Up to 2 years post BAFF-R CART cells infusion

• NMOSD: Expanded Disability Status Scale (EDSS) score

  Up to 2 years post BAFF-R CART cells infusion

Study Arms (1)

Participant Group BAFF-R CART cells

EXPERIMENTAL

Experimental: CART cells therapy，Dose level 1: 0.5 × 10\^6 CART cells/Kg The tolerability and safety of BAFF-R CART cells will be assessed in an initial dose of 0.5×10\^6 CART cells/Kg and three subjects will be enrolled firstly. Experimental: CART cells therapy，Dose level 2: 1 × 10\^6 CART cells/Kg If neither DLT nor efficacy is shown in the first three subjects, the dose of CART cells will be increased to 1 × 10\^6 CART cells/kg to assess DLT. Experimental: CART cells therapy，Dose level 3: 2 × 10\^6 CART cells/Kg If DLT occurs in two subjects, whether to test the safety and efficacy in 2 × 10\^6 CART cells/kg group will be determined by the investigator based on the initial data of efficacy, PK and PD.

Drug: BAFF-R CART

Interventions

BAFF-R CART DRUG

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.

Participant Group BAFF-R CART cells

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. Assessed by the investigator as having a refractory neuroimmune disease;
• Refractory neuroimmune diseases were defined as:
• Poor symptom control on at least three immunosuppressive agents for more than one year;
• Clinical evidence of at least two relapses within 12 months or three relapses within 24 months and one relapse within 12 months prior to screening.
• \. Male study participants must agree to use contraception during the treatment period for 1 year after receiving study treatment, and sperm donation is prohibited throughout the study period;
• \. In the case of females with childbearing potential, need to agree to use contraception during the treatment period and for at least 1 year after receiving study treatment. Participants must have a negative serum pregnancy test result at screening and a confirmed negative urine pregnancy test result prior to first CART treatment.

You may not qualify if:

• Any medical or psychiatric condition that, in the opinion of the investigator, may jeopardize the study participant or affect the study participant's ability to participate in this study;
• A history of drug or alcohol abuse within the 12 months prior to baseline, or any condition that in the opinion of the investigator is associated with poor adherence;
• Women who are breastfeeding or pregnant, or who plan to become pregnant at any time during the 12-month time period following treatment with CART, or a history of spontaneous or induced abortion within 4 weeks prior to screening;
• Study participants with a clinically relevant active infection (e.g., sepsis, pneumonia, or abscess) or serious infection (resulting in hospitalization or requiring antibiotic therapy) within 4 weeks prior to baseline;
• The study participant has received a live attenuated vaccination within 8 weeks prior to baseline; or is scheduled to receive a live vaccination (including COVID-19 vaccine) within 8 weeks after treatment;
• Study participants who have received prior treatment with rituximab within 6 months prior to baseline;
• Study participants had received tolizumab, eculizumab within 3 months prior to baseline;
• Study participants who have received intravenous human immunoglobulin, plasma exchange, undergone immunotherapy within 4 weeks prior to baseline;
• Known concomitant serious underlying diseases, such as hepatic and renal impairment, hematologic disorders, previous severe cardiovascular disease, severe hypertension, diabetes mellitus, poor control of blood pressure and blood glucose;
• Comorbid mental illness, suicidal ideation (affirmative answer (yes) to question 4 or question 5 of the Colombian Suicide Severity Rating Scale (C-SSRS) indicating a suicide attempt within the last 6 months);
• Any of the following laboratory abnormalities during the screening period (a repeat measurement may be taken during the screening period prior to randomization to confirm results); (1) Elevated liver enzymes: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN); (2) Total bilirubin \> 1.5 times the ULN; (3) Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m2; (4) CD19 + B cell count \<40 cells/µL;
• Presence of a history of tuberculosis infection, high risk of acquired tuberculosis infection;
• known immunodeficiency diseases, including human immunodeficiency virus (HIV) infection;
• Viral hepatitis B surface antigen (HBsAg) positivity during the screening period;
• Receiving blood transfusion therapy 4 weeks prior to baseline or during the screening period;

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

RECRUITING

MeSH Terms

Conditions

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Neuromyelitis Optica; Myasthenia Gravis; Myositis

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Muscular Diseases; Musculoskeletal Diseases

Study Officials

• Qiang Liu, M.D.,Ph.D

  Tianjin Medical University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiang Liu, M.D.,Ph.D

CONTACT

+86 15022439149; qliu@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Neurology

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 15, 2025
• Study Start: April 10, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

CN (1)