This single-arm, open-label investigator-initiated trial (IIT) evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of RD06-05 in patients with autoimmune neurological diseases, including Multiple Sclerosis (MS), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Autoimmune Encephalitis (AE), and other B-cell-mediated neuroautoimmune disorders. In this study, the dose of CAR-T cells administered is 10×10⁶ CAR⁺T cells per kilogram of body weight. Investigators may decide whether to add other dose groups based on the subjects' safety data, pharmacokinetic (PK) data, pharmacodynamic (PD) data, and preliminary efficacy data. For each indication, 6 to 9 subjects will be enrolled, with a total of 24 to 36 subjects planned for enrollment in the entire study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single intravenous infusion of CD19/BCMA-targeted CAR-T cells (RD06-05) at dose of 1 × 10\^7 CAR+ T cells/kg (Additional dose levels will be determined by safety, PK/PD, and preliminary efficacy).
From Day -5 to Day -3 prior to cell infusion (Day 0), subjects will receive chemotherapy preconditioning based on the "Fludarabine + Cyclophosphamide" (FC regimen). The recommended preconditioning regimen is as follows: Fludarabine: 30 mg/m² per day, once daily for 3 consecutive days; Cyclophosphamide: 300 mg/m² per day, once daily for 3 consecutive days;
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGThe incidence rates of Treatment-Emergent Adverse Events (TEAEs)
Time frame: From the start of cell infusion to 24 months after infusion
Serious Adverse Events (SAEs)
Time frame: From the start of cell infusion to 24 months after infusion
The incidence rate of Adverse Events of Special Interest (AESI)
Time frame: From the start of cell infusion to 24 months after infusion
MS:Time to first relapse; Annual Relapse Rate (ARR)
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
MS: The number of new or enlarged T2 lesions on MRI during the study;
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
MS: The number of newly emerged gadolinium-enhancing lesions on MRI
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
MS: The change in Expanded Disability Status Scale (EDSS) score from baseline during the study
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
MG: Changes in Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) scores compared to baseline
Time frame: At Week 12, and Months 6, 12, 18, and 24 post infusion
MG: Changes in Quantitative Myasthenia Gravis Score (QMG) scores compared to baseline
Time frame: At Week 12, and Months 6, 12,18, and 24 post infusion
MG: The proportion of patients with a change of ≥2 points in MG-ADL scores
Time frame: Months 12 and 24 post infusion
MG: The proportion of patients with a change of ≥3 points in Myasthenia Gravis Composite Scale (MGC) score
Time frame: Months 12 and 24 post infusion
MG: Changes in the titer of MG serum-specific autoantibodies compared to baseline
Time frame: Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
CIDP: Changes in Inflammatory Neuropathy Cause and Treatment disability scale (INCAT) score compared to baseline
Time frame: At Week 12, and Months 6, 12, 18, and 24 post infusion
CIDP: Changes in Inflammatory Rasch-Built Overall Disability Scale (I-RODS) score compared to baseline
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
CIDP: Changes in average grip strength compared to baseline
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
CIDP: Changes in Medical Research Council Scale (MRC) score compared to baseline
Time frame: Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
Changes from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
Time frame: Months 6, 12, 18, and 24 post infusion
Changes from baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI)
Time frame: Months 6, 12, 18, and 24 post infusion
Peak expansion (Cmax)
Time frame: Days 0, 4, 7, 10, Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 18, and Month 24 post infusion
Area under the curve (AUC₀-₂₈)
Time frame: Days 0, 4, 7, 10, 14, 21, and Day 28 post infusion.
AE: Changes in CASE score from baseline
Time frame: Months 6, 12, 18, and 24 post infusion
AE: Changes in MoCA scores from baseline
Time frame: Month 6, 12, 18, and 24 post infusion
Changes in CGI score from baseline
Time frame: Month 6, 12, 18, and 24 post infusion
AE: Changes in GCS score from baseline
Time frame: Month 6, 12, 18, and 24 post infusion
Changes in MMSE score from baseline
Time frame: Monthe 6, 12,18, and 24 post infusion
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