Safety and Efficacy of Second Infusion of Autologous Immunosuppressive CAR-DC Targeting FAP in the Treatment of End-stage Dilated Cardiomyopathy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- The proportion of subjects with Dose-limiting toxicity (DLT)
研究概览
简要总结
This study aims to evaluate the safety and preliminary efficacy of a second administration of fibroblast activation protein (FAP)-targeted immunosuppressive chimeric antigen receptor dendritic cells (CAR-DC) in patients with end-stage dilated cardiomyopathy.
Previous clinical research has shown that single-dose CAR-DC therapy is safe and may provide clinical benefit. However, some patients experience recurrent worsening of heart function after initial treatment. This study will assess whether a second CAR-DC infusion is safe and whether it can further improve cardiac function in this patient population.
详细描述
Heart failure is a life-threatening syndrome with high morbidity and mortality. Dilated cardiomyopathy (DCM) is a major cause of end-stage heart failure, and currently available treatments for advanced DCM remain limited.
Immune activation and myocardial fibrosis play key roles in the progression of heart failure. Targeting cardiac fibrosis through immune modulation has emerged as a potential therapeutic strategy. Our research group has developed a novel immunosuppressive chimeric antigen receptor-modified dendritic cell (CAR-DC) therapy targeting fibroblast activation protein (FAP), designed to reduce cardiac fibrosis and improve cardiac function.
Preclinical studies demonstrated that FAP-targeted immunosuppressive CAR-DC (iCDC) therapy significantly improved cardiac function and survival in animal models of heart failure, with a favorable safety profile. Based on these findings, an exploratory clinical study of single-dose iCDC infusion in patients with end-stage DCM has been conducted, and preliminary follow-up results up to three months have shown good safety and potential clinical benefit.
However, in clinical practice, patients with end-stage DCM may experience recurrent deterioration of cardiac function due to infections or other triggers. Whether a second administration of iCDC can restore or further improve cardiac function remains unknown.
Therefore, this study aims to evaluate the safety and preliminary efficacy of a second infusion of FAP-targeted immunosuppressive CAR-DC in patients with end-stage dilated cardiomyopathy who experience worsening heart function after initial treatment.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years and ≤75 years of age, with a confirmed diagnosis of dilated cardiomyopathy.
- •Patients who previously received a single infusion of immunosuppressive CAR-DC (iCDC) therapy and, at 6 months after the first treatment, failed to maintain improvement in cardiac function, with cardiac function declining to baseline levels prior to treatment. These patients should have persistent heart failure symptoms that cannot be adequately improved, with left ventricular ejection fraction (LVEF) <35%, New York Heart Association (NYHA) functional class III-IV, and INTERMACS profile 3-
- •Able to verbally confirm understanding of the risks, benefits, and alternative treatment options of the second administration of iCDC therapy, and willing to participate in the study. The participant or his/her legal representative must provide written informed consent prior to enrollment.
- •Hematocrit >30%, lymphocyte count >0.5 × 10⁹/L, and platelet count >60 × 10⁹/L.
排除标准
- •Severe renal failure or requirement for renal dialysis, or serum creatinine >2.5 mg/dL.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than 5.0 times the upper limit of normal (ULN), or total bilirubin >3 mg/dL.
- •Presence of active infections at screening, including: Active hepatitis B infection with hepatitis B virus DNA >1000 copies/mL by PCR testing; Hepatitis C virus infection; Syphilis; Human immunodeficiency virus (HIV) infection; Uncontrolled systemic fungal, bacterial, viral, or other pathogenic infections.
- •Severe hemodynamic instability (e.g., shock).
- •Known contraindications to the investigational product or study-related procedures.
结局指标
主要结局
The proportion of subjects with Dose-limiting toxicity (DLT)
时间窗: in 14 days after injection
The proportion of participants with treatment-related adverse events as assessed by CTCAE v5.0
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: in 14 days after injection
Incidence of iCDC treatment-emergent adverse events
次要结局
- Left ventricular ejection fraction (LVEF)(1, 3, 6 months after injection)
- Left ventricular ejection fraction (LVEF)(6 months after injection)
- NT-proBNP(1, 3, 6 months after injection)
- Enhanced volume (volume%)(6 months after injection)
- INTERMACS Profile(1, 3, 6 months after injection)
- Left ventricular internal diameter end systole (LVIDs)(1, 3, 6 months after injection)
- Left ventricular internal diameter end diastole (LVIDd)(1, 3, 6 months after injection)
- Left ventricular end-systolic volume (LVESV)(6 months after injection)
- Left ventricular end-diastolic volume (LVEDV)(6 months after injection)
- 6 minutes walk test (6MWT)(1, 3, 6 months after injection)
- Change in New York Heart Association (NYHA) Functional Classification(Baseline, 1 month, 3 months, and 6 months)
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score(Baseline, 1 month, 3 months, and 6 months)
- Incidence of major adverse cardiovascular events (MACE)(1, 3, 6 months after injection)
- incidence of adverse events(6 months after injection)