An Open Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LCAR-AIO CAR-T Cells for Treating Relapsed/Refractory Neurological Autoimmune Diseases
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 37
- 试验地点
- 3
- 主要终点
- Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a prospective, single-arm, open-label, dose-exploration and expansion clinical study of LCAR-AIO in adult subjects with relapsed/refractory neurological autoimmune diseases.
详细描述
This is a prospective, single-arm, open-label exploratory clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy profiles of LCAR-AIO, a chimeric antigen receptor (CAR) -T cell therapy in subjects with relapsed/refractory neurological autoimmune diseases. Patients who meet the eligibility criteria will receive LCAR-AIO infusion. The study will include the following sequential stages: screening, apheresis, pre-treatment (cell product preparation: lymphodepleting chemotherapy), treatment (LCAR AIO infusion) and follow-up.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily participate in clinical research.
- •Age 18-70 years.
- •Adequate organ function at screening.
- •Clinical laboratory values meet criteria at screening visit.
- •Indications include:
- •Have been diagnosed of MS at least 6 months before screening.
- •Fulfill relapsed/refractory MS conditions.
- •NMOSD/MOGAD:
- •Have been diagnosed of NMOSD/MOGAD at least 6 months before screening.
- •AQP-4 IgG (NMOSD), or MOG-IgG (MOGAD) should be positive by CBA (Cell based transfection immunofluorescence assay).
- •Fulfill relapsed/refractory NMOSD/MOGAD conditions.
- •Have been diagnosed of MG at least 6 months before screening.
- •AChR-IgG or MuSK-IgG should be positive.
- •Fulfill relapsed/refractory NMOSD/MOGAD conditions.
排除标准
- •Active infections such as hepatitis and tuberculosis.
- •Other autoimmune diseases.
- •Serious underlying diseases such as tumor, uncontrolled diabetes and clinically significant cardiovascular disease.
- •Female subjects who were pregnant, breastfeeding, or planning to become pregnant while participating in this study or within 1 year of receiving LCAR-AIO treatment.
研究组 & 干预措施
LCAR-AIO T Cells
Chimeric antigen receptor T cells (LCAR-AIO) Each subject will be given a single-dose LCAR-AIO cells infusion at each dose level
干预措施: LCAR-AIO T cells (Biological)
结局指标
主要结局
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: Baseline to 104 Weeks after last subject infusion
An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.
Incidence of dose-limiting toxicity (DLT)
时间窗: 30 days after LCAR-AIO infusion (Day 1)
DLTs are severe adverse events refers to any untoward medical occurred in a subject participated in a clinical investigation, which have a causal relationship with the treatment and will limit the dose escalation.
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
时间窗: Baseline to 104 Weeks after last subject infusion
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration.
Recommended Phase 2 Dose (RP2D) regimen finding
时间窗: Baseline to 104 Weeks after last subject infusion
RP2D established through dose exploratory.
Transgene Levels of LCAR-AIO CAR-T Cells
时间窗: Baseline to 104 Weeks after last subject infusion
Transgene Levels of LCAR-AIO CAR-T Cells using sensitive assay methods will be assessed
次要结局
- Annua Relapse Rate (ARR)(Baseline to 104 Weeks after last subject infusion)
- Change in Expanded Disability Status Scale (EDSS) scores from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
- Changes in Visual Acuity from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
- Changes in Visual analogue scale (VAS) pain score from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
- Changes in MSE proportion from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
- Changes in Quantitative Myasthenia Gravis Score (QMGS) from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
- Changes in Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline up to 104 weeks(Baseline to 104 Weeks after last subject infusion)
研究者
Qiubai Li
Professor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology