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Recruiting Phase 1/2

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

NCT07022197 · tracked via the Priya Life Science China tracker
Phase
Phase 1/2
Started
2025-04-10
Last updated
2026-10-16

Condition(s) studied

Chronic Inflammatory Demyelinating PolyradiculoneuropathyNMO Spectrum DisorderMyasthenia GravisIdiopathic Inflammatory Myopathies

Investigational drug(s) / intervention(s)

BAFF-R CART

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.

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
60 Years
Healthy volunteers
No
Inclusion Criteria: 1\. Assessed by the investigator as having a refractory neuroimmune disease; Refractory neuroimmune diseases were defined as: 1. Poor symptom control on at least three immunosuppressive agents for more than one year; 2. 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. 2\. 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; 3\. 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. Exclusion Criteria: 1. 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; 2. 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; 3. 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; 4. 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; 5. 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; 6. Study participants who have received prior treatment with rituximab within 6 months prior to baseline; 7. Study participants had received tolizumab, eculizumab within 3 months prior to baseline; 8. Study participants who have received intravenous human immunoglobulin, plasma exchange, undergone immunotherapy within 4 weeks prior to baseline; 9. 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; 10. 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); 11. 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; 12. Presence of a history of tuberculosis infection, high risk of acquired tuberculosis infection; 13. known immunodeficiency diseases, including human immunodeficiency virus (HIV) infection; 14. Viral hepatitis B surface antigen (HBsAg) positivity during the screening period; 15. Receiving blood transfusion therapy 4 weeks prior to baseline or during the screening period; 16. Any other condition that the investigator deems inappropriate for participation in the study.

Primary outcome measure(s)

  • Types and incidence of dose-limiting toxicity (DLT) after BAFF-R CART cells infusion — Up to 3 months post BAFF-R CART cells infusion
    To evaluate the DLT occurred within 3 months after BAFF-R CART cells infusion.
  • Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms. — Up to 2 years post BAFF-R CART cells infusion
    To evaluate the AEs occurred within 2 years after BAFF-R CART cells infusion.

Trial sites (1)

FacilityCityRegionStatus
Tianjin Medical University General Hospital Tianjin Tianjin Municipality Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07022197 on ClinicalTrials.gov ↗ ← All trials in China