Multi-center, Phase 1b/2 Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy (C-CAR168) for the Treatment of Progressive Multiple Sclerosis Refractory to Standard Therapy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 119
- 主要终点
- Incidence and Severity of Treatment-Emergent Adverse Events
研究概览
简要总结
This is a global, multicenter, Phase 1b/2 study evaluating the safety and efficacy of C-CAR168, an autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy, in participants with progressive multiple sclerosis refractory to standard-of-care therapy. The study includes participants with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to sign and date the informed consent form.
- •Male or female, 18-55 years of age, body weight >=40 kg.
- •Diagnosis of MS according to the 2024 McDonald criteria with cohort-specific progressive MS requirements.
- •Cohort 1: active SPMS; Cohort 2: PPMS or non-active SPMS.
- •Inadequate response to at least one prior high-efficacy disease-modifying therapy administered for at least 6 months.
- •Documented disability progression over the prior 24 months.
- •EDSS 3.0 to 6.5, inclusive.
- •Meets protocol-defined disease-duration, CSF, organ-function, cardiac/pulmonary, pregnancy testing, contraception, vaccination, and cellular-therapy follow-up requirements.
排除标准
- •RRMS, clinically isolated syndrome, radiologically isolated syndrome, or another diagnosis better explaining the neurologic course.
- •Alternative inflammatory demyelinating disorders, including AQP4-antibody-positive NMOSD and MOG-antibody-associated disease.
- •Active or chronic infection requiring antibiotics, or protocol-specified positive infectious disease testing.
- •Inadequate washout from prior MS therapy or specified recent immunomodulatory treatments.
- •Prior CAR T-cell therapy, other genetically modified immune cell therapy, or gene therapy.
- •Pregnant or breastfeeding, or planning pregnancy during the protocol-defined follow-up period.
- •Specified major cardiovascular, neurologic, transplant, malignancy, bleeding/thromboembolic, allergy, or protocol-compliance exclusions.
研究组 & 干预措施
C-CAR168
Participants will receive:
Leukapheresis Fludarabine Cyclophosphamide Single intravenous infusion of C-CAR168
干预措施: C-CAR168 (Drug)
结局指标
主要结局
Incidence and Severity of Treatment-Emergent Adverse Events
时间窗: Through Month 24
Incidence and severity of treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, CRS, ICANS, adverse events of special interest, and treatment- or procedure-related adverse events.
Proportion of Participants With 6-Month Composite Confirmed Disability Progression (6m-cCDP) Through Month 12
时间窗: Through Month 12
Proportion of participants within each Phase 2 cohort experiencing 6-month composite confirmed disability progression through Month 12
次要结局
- Time to first 6m-cCDP(Through Month 24)
- MRI lesion changes(Through Month 24)
- Change from baseline in 9-Hole Peg Test (9-HPT)(Month 12 and Month 24)
- Time to first 3m-cCDP(Through Month 24)
- Proportion of participants with 6m-cCDP - Through Month 12 (Phase 1b)(Through Month 12 (Phase 1b))
- Proportion of participants with 3m-cCDP(Through Month 24)
- Proportion of participants with 6m-cCDP(Through Month 24)
- Change from baseline in Expanded Disability Status Scale EDSS)(Through Month 24)
- Change from baseline in Functional Systems Score (FSS)(Through Month 24)
- Change from baseline in Timed 25-Foot Walk (T25FW)(Through Month 24)
- Incidence and severity of adverse events and serious adverse events(Through Month 24)
- Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)(Through Month 24)
- Pharmacokinetics of C-CAR168 utilizing flow cytometry(Through Month 24)