An Exploratory Clinical Study of Universal STAR-T Cell Injection in Subjects With Generalized Myasthenia Gravis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Type, 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, single-arm, open-label, dose-escalation and dose-expansion study.
This is an exploratory clinical study of universal STAR-T cell injection in patients with refractory generalized myasthenia gravis (GMG). Approximately 10-24 participants aged 18-65 years (inclusive) with the condition are planned to be enrolled.
The primary objective is to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetic/pharmacodynamic (PK/PD) profile, and immunogenicity of universal STAR-T cell injection. The starting dose is 1.5E6 STAR+ T cells/kg, administered as a single intravenous infusion.Based on safety, PK results, and preliminary efficacy data obtained from the initial dose cohorts, a recommended dose will be selected for subsequent dose-expansion studies to further systematically evaluate the safety and efficacy of universal STAR-T cell injection.
This study includes the screening period (from D-28 to D-6), the pre-clearance treatment and rest observation period (from D-5 to D-1), the cell infusion and main study endpoint observation period (from D0 to W12 after infusion), and the follow-up period (from W12 after infusion to W104).
The study is being conducted at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
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
- •Subjects must meet all the following inclusion criteria to be enrolled in this study:
- •Age 18-65 years (inclusive), gender (no gender restriction);
- •Previously diagnosed with Generalized Myasthenia Gravis (GMG), meeting the 2020 MGFA diagnostic criteria, with MG-ADL total score ≥6 and ocular-related subscore <50% of the total score, positive relevant antibodies, MGFA classification Grade II-IV, and having received at least 2 kinds of immunosuppressants or biological agents for standardized treatment;
- •Have received MG treatment for at least 3 months and present with any of the following conditions:
- •MG-ADL total score increased by ≥2 points, and no single ocular item increased by >1 point;
- •QMGS total score increased by ≥3 points, or ≥2 non-ocular items each increased by ≥1 point;
- •Increased dose of MG-related drugs, hospitalization, or emergency intervention required due to MG exacerbation;
- •Function of important organs meets the following requirements:
- •Bone marrow function:
- •Absolute neutrophil count ≥1×10⁹/L (no colony-stimulating factor treatment within 2 weeks before testing);
- •Hemoglobin ≥80 g/L (excluding neutropenia caused by disease);
- •Liver function: ALT ≤3×ULN (elevated ALT due to disease is excluded); AST ≤3×ULN (elevated AST due to disease is excluded); TBIL ≤1.5×ULN (elevated TBIL due to disease is excluded);
- •Renal function: Serum creatinine (CrCl) ≥45 mL/min (calculated by Cockcroft-Gault formula; acute CrCl decrease due to disease is excluded);
- •Coagulation function: International Normalized Ratio (INR) ≤1.5×ULN; Prothrombin Time (PT) ≤1.5×ULN;
- •Cardiac function: Systolic blood pressure >90 mmHg, no need for vasoactive drug maintenance;
- •Female subjects of childbearing potential and their male partners (of childbearing age) must use medically recognized contraceptive measures or abstain from sex during the study treatment period and for at least 12 months after the end of study treatment; female subjects of childbearing age must have a negative serum HCG test within 7 days before enrollment and not be in lactation;
- •Voluntarily participate in this clinical study, sign the informed consent form, be compliant, and cooperate with follow-up.
排除标准
- •Subjects who meet any of the following exclusion criteria will be excluded from this study:
- •Have used immunomodulatory or immunosuppressive drugs with therapeutic effects on the disease within 5 half-lives before enrollment, or biologics within 4 weeks (except for those who have received rituximab, with the last use of rituximab <3 months prior [B-cell reconstitution is excluded]);
- •Have a history of severe drug allergy or allergic constitution;
- •Have uncontrolled or requiring treatment for fungal, bacterial, or viral infections;
- •Have active tumor lesions at screening;
- •Have cardiac insufficiency (New York Heart Association [NYHA] functional class >II), and cannot tolerate platelet and cellular transfusions;
- •Have congenital immunodeficiency;
- •Have a history of malignant tumor (except for cured cutaneous basal cell carcinoma or cervical carcinoma in situ);
- •Have end-stage renal failure;
- •Positive for Hepatitis B surface Antigen (HBsAg), or positive for Hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA level or titer above the cutoff value for positive specimens; positive for Hepatitis C virus (HCV) antibody with peripheral blood HCV RNA positive; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis testing;
- •Pregnant or planning to become pregnant during the study or within 2 years after the end of study treatment (for both male and female subjects);
- •Investigators consider there are other reasons that should not be included in this study.
结局指标
主要结局
Type, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs).
时间窗: AEs observation will be follow-up for 24 weeks. The observation period is extended to 104 weeks.
Characterization of treatment-emergent adverse events (TEAEs) graded by NCI-CTCAE v6.0, including laboratory abnormalities, vital sign changes, and infusion-related reactions.
Incidence of Dose-Limiting Toxicities (DLTs).
时间窗: Within 28 days after infusion
To assess the safety and tolerability of \[Drug Name\] and determine the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D). DLTs are defined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v6.0.
次要结局
- Change in Myasthenia Gravis Quantitative Scale (QMG) or Myasthenia Gravis Activities of Daily Living (MG-ADL) Scores.(The efficacy endpoint evaluation for 104 weeks.)
- Maximum Plasma Concentration of Universal STAR-T Cells (Cmax)(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- Time to Reach Maximum Plasma Concentration (Tmax) of Universal STAR-T Cells.(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- Area Under the Plasma Concentration-Time Curve (AUC) of Universal STAR-T Cells.(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- Change in Serum Cytokine Concentrations (IL-1β, IL-6, etc.) as a PD Biomarker.(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- PD Biomarker Level Change (B cells Quantification and Phenotypic).(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- Immunogenicity: Anti-Drug Antibodies (ADA) against universal STAR-T cells.(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
- Change in Replication-Competent Adeno-Associated Virus (RCA) Concentration in Peripheral Blood.(Up to 24 weeks (Core Analysis Period); Extended observation up to 104 weeks.)
研究者
Daishi Tian
Deputy Director of the Department of Neurology, Tongji Hospital
Tongji Hospital