NCT06704269进行中（未招募）1 期
An Open-label, Multi-center, Phase I/II Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Treatment-resistant Generalized Myasthenia Gravis
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 26
- 主要终点
- Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a phase I/II study to assess safety, efficacy, and cellular kinetics of YTB323 in participants with treatment-resistant generalized myasthenia gravis. YTB323 is a Biological CAR-T cell therapy.
详细描述
This is an open-label, multi-center, non-confirmatory study intended to assess safety, efficacy, and cellular kinetics of YTB323 treatment in participants with treatment-resistant generalized myasthenia gravis in order to enable a benefit to risk assessment for further development in generalized myasthenia gravis (gMG). The study plans to enroll approximately 15 participants with treatment-resistant gMG. The study utilizes a single dose design across 2 cohorts, consisting of a sentinel cohort of 3 patients followed by an expansion cohort of an additional 12 patients.
All participants dosed with YTB323 will be followed until 15 years after YTB323 administration in the Long-Term Follow-up (LTFU).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed gMG diagnosis supported by the following:
- •Documented report of positive serology testing for either AChR antibodies or MuSK antibodies at screening AND at least one of the following:
- •History of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography
- •History of positive acetylcholinesterase inhibitor test
- •Improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician
- •MGFA Class III-IVa (gMG) at screening
- •Treatment-resistant gMG as defined by: MG-ADL score ≥ 6 (≥50% non-ocular) at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy.
- •If on chronic corticosteroids, must be on a stable dose of corticosteroids for ≥1 month prior to screening and have the ability and willingness to taper to a maximum dose of 10 mg prednisolone daily or equivalent at least one week before leukapheresis
- •If treated with cholinesterase inhibitors, patients must be on a stable dose for at least two weeks prior to screening
排除标准
- •Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V at screening
- •History of bone marrow/hematopoietic stem cell or solid organ transplantation.
- •Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis
- •Other uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, at screening
- •Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody, at screening
- •Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
YTB323
Experimental
YTB323 single intravenous (i.v.) infusion
干预措施: YTB323 (Genetic)
结局指标
主要结局
Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 2 years
Incidence of AE's, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANs), changes in Vital Signs, Laboratory parameters, ECG, and neurological status qualifying and reported as AEs.
次要结局
- Plasma Pharmacokinetics (PK) of YTB323 - CMAX(Pre-dose Day 1 up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - Clast(Pre-dose Day 1 up to 2 years)
- Cellular immunogenicity of YTB323(Pre-dose lymphodepletion up to 2 years)
- Humoral immunogenicity of YTB323(Pre-dose lymphodepletion up to 2 years)
- Change from Baseline of MG-ADL score(Baseline up to 2 years)
- Change from Baseline of QMG total score(Baseline up to 2 years)
- Proportion of patients with a ≥3-point reduction of QMG total score sustained for 6 months post Baseline(Baseline up to 2 years)
- Proportion of patients with a ≥2-point reduction of MG-ADL score sustained for 6 months post Baseline(Baseline up to 2 years)
- Proportion of patients with a MGFA-PIS of minimal manifestations (MM) or better and sustained for 6 months post Baseline(Baseline up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - Clast(Pre-dose Day 1 up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - CMAX(Pre-dose Day 1 up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - AUC(Pre-dose Day 1 up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - Tmax(Pre-dose Day 1 up to 2 years)
- Plasma Pharmacokinetics (PK) of YTB323 - Tlast(Pre-dose Day 1 up to 2 years)
- Cellular immunogenicity of YTB323(Pre-dose lymphodepletion up to 2 years)
- Humoral immunogenicity of YTB323(Pre-dose lymphodepletion up to 2 years)
- Neutralizing immunogenicity of YTB323(Pre-dose lymphodepletion up to 2 years)
- Change from Baseline of MG-ADL score(Baseline up to 2 years)
- Change from Baseline of QMG total score(Baseline up to 2 years)
- Proportion of patients with a ≥3-point reduction of QMG total score sustained for 6 months post Baseline(Baseline up to 2 years)
- Proportion of patients with a ≥2-point reduction of MG-ADL score sustained for 6 months post Baseline(Baseline up to 2 years)
- Proportion of patients with a MGFA-PIS of minimal manifestations (MM) or better and sustained for 6 months post Baseline(Baseline up to 2 years)
研究者
研究点 (26)
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