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

Detailed Description

This study aims to evaluate the safety and efficacy of fibroblast activation protein (FAP)-targeted immunosuppressive chimeric antigen receptor-dendritic cell (iCDC) therapy in patients with end-stage dilated cardiomyopathy, and to provide a novel therapeutic approach for this condition. This is a prospective, single-center, open-label, two-phase clinical study designed to assess the safety and preliminary efficacy of iCDC in patients with end-stage dilated cardiomyopathy.

Phase 1 employs a single-arm, 3+3 dose-escalation design. iCDC therapy will be administered at predefined dose levels to evaluate safety, dose-limiting toxicities, treatment-related adverse events, and preliminary efficacy, and to determine the safe and effective dose.

Phase 2 will expand enrollment at the safe and effective dose identified in Phase 1. Additional patients will receive iCDC therapy at this dose, and a non-randomized concurrent control group will also be enrolled. Control participants must meet the same eligibility criteria and, after providing informed consent, choose not to receive iCDC therapy but agree to participate in study follow-up. They will not undergo leukapheresis, iCDC manufacturing, or cell infusion, and will continue to receive guideline-directed standard medical therapy. The iCDC treatment group will be assessed for safety and preliminary efficacy. The concurrent control group will be followed using clinically feasible shared assessments, including echocardiography, BNP or NT-proBNP, 6-minute walk distance, NYHA functional class, INTERMACS profile, KCCQ score, worsening heart failure, hospitalization, death, and major cardiovascular events. Cardiac magnetic resonance imaging and cell therapy-specific assessments will be performed exclusively in participants receiving iCDC therapy and will not be included in between-group comparisons with the control group.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jiamin Li, MD; Phone Number: 86-18868112006; Email: 21818216@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Xinyang Hu; Phone Number: 86-0571-87783777; Email: hxy0507@zju.edu.cn

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: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iCDC Therapy; Participants in this arm will receive FAP-targeted immunosuppressive chimeric antigen receptor-dendritic cell (iCDC) therapy. In Phase 1, iCDC will be administered at predefined dose levels (1×10⁵, 4×10⁵, and 8×10⁵ cells/kg) using a modified single-arm 3+3 dose-escalation design. Safety and preliminary efficacy will be evaluated at each dose level. If a given dose level is deemed safe and effective at 1 month post-treatment, it will be selected as the safe and effective dose, and no further dose escalation will be pursued. Otherwise, dose escalation may proceed to the next predefined level in accordance with the protocol. In Phase 2, additional participants will receive iCDC therapy at the safe and effective dose identified in Phase 1.	Biological: FAP immunosuppressive CAR-DC; Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion
No Intervention: Control; Participants in this arm will be enrolled in Phase 2 as a non-randomized concurrent control group. They must meet the eligibility criteria and, after providing informed consent, elect not to receive iCDC therapy but agree to study follow-up. These participants will not undergo leukapheresis, iCDC manufacturing, or cell infusion, and will continue to receive guideline-directed standard medical therapy. They will be followed using clinically feasible shared assessments for exploratory comparison with the iCDC therapy arm.

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, 12 months after injection
Left ventricular ejection fraction (LVEF)	The difference of LVEF from baseline. LVEF will be assessed by Cardiac Magnetic Resonance (CMR).	6, 12 months after injection
Enhanced volume (volume%)	The difference of Enhanced volume (volume%) from baseline. Enhanced volume will be assessed by CMR.	6 , 12 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 , 12 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 , 12 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 , 12 months after injection
Left ventricular end-systolic volume (LVESV)	The difference of LVESV from baseline. LVESV will be assessed by CMR.	6 , 12 months after injection
Left ventricular end-diastolic volume (LVEDV)	The difference of LVEDV from baseline. LVEDV will be assessed by CMR.	6 , 12 months after injection
NT-proBNP	Analysis of differences of NT-proBNP serum level from baseline.	1, 3, 6 , 12 months after injection
6 minutes walk test (6MWT)	The difference of 6MWT from baseline.	1, 3, 6 , 12 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, 12 months after injection
Incidence of major adverse cardiovascular events (MACE)	Incidence of Cardiac death, readmission due to heart failure.	1, 3, 6, 12 months after injection
incidence of adverse events	Incidence of adverse events of heart, nerve system, mental system, digestive system and immune system.	6, 12 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 (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028

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): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 12, 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