NCT06902896

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

To study the safety and efficacy of fibroblast activation protein (FAP)-targeted immunosuppressive chimeric antigen receptor-dendritic cell (CAR-DC) in the treatment of end-stage dilated cardiomyopathy and provide a new method for the treatment of end-stage dilated cardiomyopathy.

Detailed description

Background: Immune system activation and myocardial fibrosis are widely observed in patients with heart failure, whether it is ischemic or non-ischemic heart failure. Therefore, targeting inflammation and cardiac fibrosis may become a universal therapeutic strategy for the treatment of heart failure. At present, T cell surface molecular group modification (such as CAR-T) has been found to reduce fibrosis and restore cardiac function after injury in rodent heart failure models, suggesting that immune cells may be one of the potential effective targets for the treatment of heart failure. Dendritic cells (DCs) are the most powerful professional antigen-presenting cells in the body. Immature DCs have strong migration ability, and mature DCs can effectively activate naive T cells, which are at the center of initiating, regulating, and maintaining immune responses. Studies have confirmed that dendritic cells are involved in regulating inflammatory responses after myocardial injury. Here, we innovatively applied chimeric antigen receptor (CAR) technology to edit DCs, making the new CAR immune cells exhibit an immunosuppressive phenotype, leading to T cell tolerance to CAR immune cells without producing new antigens; and targeting fibroblast activation protein (FAP) to accumulate in the fibrotic area of cardiac injury, thereby reducing fibrosis and enhancing cardiac function. Purpose: To evaluate the efficacy and safety of immunosuppressive CAR-DC (iCDC) in the treatment of patients with end-stage dilated cardiomyopathy. Study design: This study is a prospective, single-center, single-arm clinical study. The study objects are patients aged 18 to 75 years with end-stage dilated cardiomyopathy (ejection fraction \< 35%) who visited the Department of Cardiology. In this study, patients with end-stage dilated cardiomyopathy were proposed to undergo FAP iCDC Cell therapy. Outcome measure: The primary outcome is evaluation of the safety of FAP iCDC for end-stage dilated cardiomyopathy. The secondary outcomes are left ventricular ejection fraction (LVEF) assessed by echocardiography and cardiac magnetic resonance, enhanced volume assessed by cardiac magnetic resonance, interagency registry for mechanically assisted circulatory support (INTERMACS) grade, left ventricular internal dimension in systole (LVIDs), left ventricular internal dimension in diastole (LVIDd), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), N-terminal prohormone of brain natriuretic peptide (NT pro-BNP), 6 minutes walk test (6-MWT), New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, incidence of major adverse cardiac events (MACE) and adverse events.

Conditions

• Dilated Cardiomyopathy (DCM)
• Heart Failure

Interventions

Type	Name	Description
BIOLOGICAL	FAP immunosuppressive CAR-DC	Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion

Timeline

• Start date: 2025-04-22
• Primary completion: 2025-10-12
• Completion: 2026-03-25
• First posted: 2025-03-30
• Last updated: 2026-04-06

Locations

1 site across 1 country: China