A Phase 1/2 Dose Escalation and Expansion Study of CRT-402, an In Vivo CD19 Targeted CAR-T Therapy, in Refractory Autoimmune Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), and dose-limiting toxicities (DLTs).
研究概览
简要总结
Patients with refractory autoimmune diseases often have limited treatment options and ongoing disease activity despite standard therapies. CRT-402 is an in vivo Cluster of differentiation 19 (CD19)-targeted CAR-T cell therapy designed to deplete CD19-positive B cells and promote immune system reset. This study evaluates the safety, tolerability, preliminary efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of CRT-402 in participants with active refractory systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM).
详细描述
This is a multicenter, open-label, Phase 1/2, first-in-human, dose escalation and expansion study designed to assess the safety and tolerability, as well as define the recommended Phase 2 dose (RP2D) of CRT-402 in participants with refractory autoimmune disease.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older.
- •Diagnosis of active, refractory systemic lupus erythematosus, systemic sclerosis, or idiopathic inflammatory myopathy meeting established classification criteria, with inadequate response or intolerance to standard therapy.
- •Adequate renal, hepatic, cardiac, and pulmonary function per protocol-defined criteria.
- •Participants of reproductive potential must agree to use protocol-specified contraception during the study and for a defined period after dosing.
- •Females of childbearing potential must have a negative pregnancy test before treatment.
- •Must be willing and able to attend study visits and follow all study requirements.
排除标准
- •Clinical suitability for a less burdensome and/or approved therapeutic approach, as judged by the Investigator,
- •Any medical condition or laboratory abnormality that, in the Investigator's judgment, would place the participant at unacceptable risk or confound interpretation of study data,
- •Prior Cluster of differentiation 19 (CD19)-directed, cell, or gene therapy,
- •History of bone marrow/ hematopoietic stem cell or solid organ transplantation,
- •Active or inadequately treated infection, including Human immunodeficiency (HIV), hepatitis B or C, or tuberculosis,
- •Pregnancy or lactation.
研究组 & 干预措施
CRT-402
Participants will receive CRT-402 by intravenous infusion. Dose escalation will proceed according to protocol-defined safety criteria.
干预措施: CRT-402 (Drug)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), and dose-limiting toxicities (DLTs).
时间窗: Up to 52 weeks
Adverse events (AEs) are any new or worsening medical problems that occur after starting the study treatment.
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
时间窗: Up to 52 weeks
cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome ICANS will be graded using standard consensus criteria.
次要结局
- Overall Response Rate (ORR), measured by disease-specific composite response criteria.(Week 24)
- Pharmacokinetic parameter: Volume of distribution (Vd)(Day 1 through Day 22)
- Pharmacokinetic parameter: Mean Residence Time (MRT)(Day 1 through Day 22)
- Pharmacokinetic parameter: Apparent terminal half-life (t1/2)(Day 1 through Day 22)
- Pharmacokinetic parameter: Terminal elimination rate constant (λz).(Day 1 through Day 22)
- Assess emergence of anti-drug antibodies (ADAs)(Up to 52 weeks)
- Pharmacokinetic parameter: Maximum observed plasma concentration (Cmax)(Day 1 through Day 22)
- Pharmacokinetic parameter: Area under the curve (AUC)(Day 1 through Day 22)
- Pharmacokinetic parameter: Time to Maximum Concentration (tmax)(Day 1 through Day 22)
- Pharmacokinetic parameter: Plasma clearance (CL)(Day 1 through Day 22)