Clinical trial NCT07022197: Safety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases
Official title: Safety and Efficacy of BAFF-R CART for Refractory Neuroimmune Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
NMO Spectrum Disorder
Myasthenia Gravis
Idiopathic Inflammatory Myopathies
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2025-06-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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).

Eligibility criteria: 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 outcomes:
measure: Types and incidence of dose-limiting toxicity (DLT) after BAFF-R CART cells infusion
timeFrame: Up to 3 months post BAFF-R CART cells infusion
measure: Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms.
timeFrame: Up to 2 years post BAFF-R CART cells infusion
Secondary outcomes:
measure: PD-Soluble BAFF
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: PD-Pathogenic antibody
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: PD-Nfl（MS）
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: PK-VCN
timeFrame: Up to 15 years post BAFF-R CART cells infusion
measure: PK-BAFF-R CAR-T cells
timeFrame: Up to 2 years post BAFF-R CART cells infusion
Other outcomes:
measure: NMOSD: the number of attacks
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: NMOSD: Accumulated total active MRI lesions
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: NMOSD: Expanded Disability Status Scale (EDSS) score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: NMOSD: Modified Rankin Scale
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: NMOSD: Visual acuity
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MG: Quantitative Myasthenia Gravis Score (QMG)
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MG: Myasthenia Gravis Activities if Daily Living (MG-ADL) Score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: CIDP: Inflammatory Neuropathy Cause and Treatment (INCAT) Score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: CIDP: Medical Research Council (MRC) muscle function Score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: CIDP: Assess changes in nerve conduction test results
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: IMNM: Manual Muscle Testing (MMT) Score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: IMNM: Assess the changes in serum creatine kinase levels in patients with IMNM before and after treatment.
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: IMNM: Muscle MRI
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: 36-item Short Form Generic Health Survey (SF-36) score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: EuroQol-five dimensions (EQ-SD) score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Visual analogue scale (VAS) pain score
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Annual hospitalization rates
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Cytokines release after BAFF-R CART cells infusion
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Immunogenicity of BAFF-R CART cells
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Detection of RCL
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: Profiling of cell subtypes
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Annualized Relapse Rate (ARR)
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Time to first relapse
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Number of T1 Gadolinium (Gd)
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Annualized rate of T2 lesions
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Percent Change in T2 lesions volume
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Change in EDSS
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: Percent of NEDA-3
timeFrame: Up to 2 years post BAFF-R CART cells infusion
measure: MS: 3-month CDP
timeFrame: Up to 3 months post BAFF-R CART cells infusion
measure: MS: 6-month CDP
timeFrame: Up to 6 months post BAFF-R CART cells infusion
measure: MS: Patient Reported Outcomes (PRO)
timeFrame: Up to 2 years post BAFF-R CART cells infusion
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Qiang Liu, M.D.,Ph.D
role: PRINCIPAL_INVESTIGATOR
References: