Safety and Efficacy of Second Infusion of FAP iCDC in End-stage Dilated Cardiomyopathy

Phase 1Not Yet RecruitingNCT07516288

Second Affiliated Hospital, School of Medicine, Zhejiang University5 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ≥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 3-6. * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

The proportion of subjects with Dose-limiting toxicity (DLT)

The proportion of participants with treatment-related adverse events as assessed by CTCAE v5.0

Time frame: in 14 days after injection

Incidence of treatment-emergent adverse events (TEAEs)

Incidence of iCDC treatment-emergent adverse events

Time frame: in 14 days after injection

Secondary Outcomes

Left ventricular ejection fraction (LVEF)

The difference of LVEF from baseline. LVEF will be assessed by echocardiography.

Time frame: 1, 3, 6 months after injection

Left ventricular ejection fraction (LVEF)

The difference of LVEF from baseline. LVEF will be assessed by Cardiac Magnetic Resonance (CMR).

Time frame: 6 months after injection

Enhanced volume (volume%)

The difference of Enhanced volume (volume%) from baseline. Enhanced volume will be assessed by CMR.

Time frame: 6 months after injection

INTERMACS Profile

Profile 1. Critical cardiogenic shock; Profile 2. Progressive decline on inotropic support; Profile 3. Stable but inotrope dependent; Profile 4. Resting symptoms home on oral therapy; Profile 5. Exertion Intolerant; Profile 6. Exertion Limited; Profile 7. Advanced NYHA Class III symptoms

Time frame: 1, 3, 6 months after injection

Left ventricular internal diameter end systole (LVIDs)

The difference of LVIDs from baseline. LVIDs will be assessed by echocardiography.

Time frame: 1, 3, 6 months after injection

Left ventricular internal diameter end diastole (LVIDd)

The difference of LVIDd from baseline. LVIDd will be assessed by echocardiography.

Time frame: 1, 3, 6 months after injection

Left ventricular end-systolic volume (LVESV)

The difference of LVESV from baseline. LVESV will be assessed by CMR.

Time frame: 6 months after injection

Left ventricular end-diastolic volume (LVEDV)

The difference of LVEDV from baseline. LVEDV will be assessed by CMR.

Time frame: 6 months after injection

NT-proBNP

Analysis of differences of NT-proBNP serum level from baseline.

Time frame: 1, 3, 6 months after injection

6 minutes walk test (6MWT)

The difference of 6MWT from baseline.

Time frame: 1, 3, 6 months after injection

Change in New York Heart Association (NYHA) Functional Classification

Assessment of heart failure symptom severity using the New York Heart Association (NYHA) functional classification. NYHA class ranges from I to IV, with higher classes indicating worse functional status.

Time frame: Baseline, 1 month, 3 months, and 6 months

Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score

Assessment of heart failure-related health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ score ranges from 0 to 100, with higher scores indicating better health status and quality of life.

Time frame: Baseline, 1 month, 3 months, and 6 months

Incidence of major adverse cardiovascular events (MACE)

Incidence of Cardiac death, readmission due to heart failure.

Time frame: 1, 3, 6 months after injection

incidence of adverse events

Incidence of adverse events of heart, nerve system, mental system, digestive system and immune system.

Time frame: 6 months after injection

Safety and Efficacy of Second Infusion of FAP iCDC in End-stage Dilated Cardiomyopathy

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts