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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Dilated Cardiomyopathy (DCM)
• Intervention / Treatment: Biological: FAP immunosuppressive CAR-DC

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 years old and 75 years old, diagnosed with dilated cardiomyopathy.
• Able to verbally confirm that he/she understands the risks, benefits and treatment options of the iCDC trial. He/she or his/her legal representative provides written informed consent before participating in the clinical trial.
• Diagnosed with Heart Failure with reduced ejection fraction (HFrEF), optimized drug therapy (under maximum tolerance of GDMT) for at least 3 months, left ventricular ejection fraction <35%, NYHA functional class ⅢB-IV, INTERMACS class 3-6.
• Blood test: hematocrit >30%, lymphocytes >0.5×10^9/L, platelets >60×10^9/L.

Exclusion Criteria:

• History of myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks before enrollment.
• CRT implanted within 12 weeks before enrollment or intended to implant CRT device.
• Previous heart transplantation or implantation of a ventricular assist device or similar device, or planned implantation of a ventricular assist device or similar device.
• Heart failure caused by ischemic cardiomyopathy, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, long-standing hypertension, congenital structural heart disease, or uncorrected primary valvular disease.
• Symptomatic bradycardia or second/third degree heart block.
• Active autoimmune disease requiring immunosuppressive therapy.
• Pulmonary Embolism (PE).
• A history of tuberculosis.
• History of severe renal failure or need for dialysis, creatinine >2.5 mg/dl.
• Uncorrected thrombocytopenia or systemic coagulopathy (platelet count < 50,000, INR > 2.5, or aPTT > 2.5 times control in the absence of anticoagulation), or active bleeding and uncorrectable coagulopathy.
• Aspartate aminotransferase or alanine aminotransferase levels greater than 5.0 times the upper limit of normal (ULN), total bilirubin >3 mg/dl.
• History of concurrent severe infection, hepatobiliary obstruction, or malignancy.
• Infections: Active hepatitis B (PCR-detected hepatitis B virus DNA copies > 1000), hepatitis C, syphilis, or human immunodeficiency virus (HIV) infection at screening; uncontrolled systemic fungal, bacterial, viral, or other pathogen infection.
• Severe hemodynamic instability (eg, shock).
• Women who are pregnant or may become pregnant.
• Contraindications to study drugs or tests.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: dilated cardiomyopathy; Administration of FAP immunosuppressive CAR-DC cell therapy in dilated cardiomyopathy. Patients are planned to be enrolled in the dose-escalation trial (1×10^5/kg、4×10^5/kg、and 8×10^5/kg) .The first dose group (4×10⁵/kg) initially enrolls 3 subjects to observe Dose-Limiting Toxicity (DLT) responses.; If no DLT occurs and all 3 subjects demonstrate efficacy after 6 months of treatment, and this dose is determined as the safe and effective dose.; If 1 subject experiences DLT, 3 additional subjects are enrolled.If 1/6 subjects develops DLT, and efficacy is not fully achieved in all 6 subjects, escalate to the next dose group (8×10^5/kg).If ≥2/6 subjects develop DLT, de-escalate to the previous dose group (1×10^5/kg). （3）After identifying a safe and effective dose, enrollment will be expanded at this dose to bring the total sample size to 8-10 subjects, to further evaluate safety and efficacy.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with Dose-limiting toxicity (DLT)	The proportion of participants with treatment-related adverse events as assessed by CTCAE v5.0	in 14 days after injection
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of iCDC treatment-emergent adverse events	in 14 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction (LVEF)	The difference of LVEF from baseline. LVEF will be assessed by echocardiography.	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).	6 months after injection
Enhanced volume (volume%)	The difference of Enhanced volume (volume%) from baseline. Enhanced volume will be assessed by CMR.	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	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.	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.	1, 3, 6 months after injection
Left ventricular end-systolic volume (LVESV)	The difference of LVESV from baseline. LVESV will be assessed by CMR.	6 months after injection
Left ventricular end-diastolic volume (LVEDV)	The difference of LVEDV from baseline. LVEDV will be assessed by CMR.	6 months after injection
NT-proBNP	Analysis of differences of NT-proBNP serum level from baseline.	1, 3, 6 months after injection
6 minutes walk test (6MWT)	The difference of 6MWT from baseline.	1, 3, 6 months after injection
assessment of heart failure symptom	The difference of heart failure symptom, which will be assessed by NYHA grading and KCCQ score.	1, 3, 6 months after injection
Incidence of major adverse cardiovascular events (MACE)	Incidence of Cardiac death, readmission due to heart failure.	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.	6 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Xinyang Hu, PhD, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2025
• Primary Completion (Actual): October 12, 2025
• Study Completion (Actual): March 25, 2026

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: end-stage dilated cardiomyopathy; FAP immunosuppressive CAR-DC
• Additional Relevant MeSH Terms: Laminopathies; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Cardiomyopathies; Cardiomegaly; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Failure; Cardiomyopathy, Dilated; Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents
• Other Study ID Numbers: YAN2024-1210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No