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

NCT06902896 | Recruiting Phase 1 DMC

• 1 other identifier: YAN2024-1210
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dilated Cardiomyopathy (DCM); Heart Failure

Keywords

end-stage dilated cardiomyopathy; FAP immunosuppressive CAR-DC

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• Left ventricular ejection fraction (LVEF)

  1, 3, 6, 12 months after injection

• Left ventricular ejection fraction (LVEF)

  6, 12 months after injection

• Enhanced volume (volume%)

  6 , 12 months after injection

• INTERMACS Profile

  1, 3, 6 , 12 months after injection

• Left ventricular internal diameter end systole (LVIDs)

  1, 3, 6 , 12 months after injection

Study Arms (2)

iCDC Therapy

EXPERIMENTAL

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

Control

NO INTERVENTION

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.

Interventions

FAP immunosuppressive CAR-DC BIOLOGICAL

Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion

iCDC Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Xinyang Hu, PhD

  2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiamin Li, MD

CONTACT

86-18868112006; 21818216@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two-phase interventional study. Phase 1 will employ a modified single-arm 3+3 dose-escalation design to evaluate the safety, dose-limiting toxicities, treatment-related adverse events, and preliminary efficacy of iCDC therapy, and to establish a safe and effective dose for further evaluation. Once the safe and effective dose is determined, enrollment at that dose will be expanded to a total of 8-10 participants in Phase 1 to further assess safety and preliminary efficacy. In Phase 2, the study will be expanded at the safe and effective dose identified in Phase 1. An additional 15 participants will receive iCDC therapy at this dose, and 20 participants will be enrolled as a non-randomized concurrent control group for exploratory comparison.

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 30, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 14, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)