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

Official title

Safety and Efficacy of Second Infusion of Autologous Immunosuppressive CAR-DC Targeting FAP in the Treatment of End-stage Dilated Cardiomyopathy

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.

Detailed description

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.

Interventions

• Biological FAP immunosuppressive CAR-DC
  Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion

Primary outcome measures

• The proportion of subjects with Dose-limiting toxicity (DLT) [Time frame: in 14 days after injection]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: in 14 days after injection]

Secondary outcome measures (12)

• Left ventricular ejection fraction (LVEF) [Time frame: 1, 3, 6 months after injection]
• Left ventricular ejection fraction (LVEF) [Time frame: 6 months after injection]
• Enhanced volume (volume%) [Time frame: 6 months after injection]
• INTERMACS Profile [Time frame: 1, 3, 6 months after injection]
• Left ventricular internal diameter end systole (LVIDs) [Time frame: 1, 3, 6 months after injection]
• Left ventricular internal diameter end diastole (LVIDd) [Time frame: 1, 3, 6 months after injection]
• Left ventricular end-systolic volume (LVESV) [Time frame: 6 months after injection]
• Left ventricular end-diastolic volume (LVEDV) [Time frame: 6 months after injection]
• NT-proBNP [Time frame: 1, 3, 6 months after injection]
• 6 minutes walk test (6MWT) [Time frame: 1, 3, 6 months after injection]
• Change in New York Heart Association (NYHA) Functional Classification [Time frame: Baseline, 1 month, 3 months, and 6 months]
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score [Time frame: Baseline, 1 month, 3 months, and 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT07516288 · YAN2026-0117

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗