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Recruiting NCT06902896

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

Phase I / Phase II Interventional Dilated Cardiomyopathy (DCM) Heart Failure

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: FAP immunosuppressive CAR-DC.
Who it may be relevant to
Registry conditions: Dilated Cardiomyopathy (DCM), Heart Failure. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

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

Overview

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

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.

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, 12 months after injection]
  • Left ventricular ejection fraction (LVEF) [Time frame: 6, 12 months after injection]
  • Enhanced volume (volume%) [Time frame: 6 , 12 months after injection]
  • INTERMACS Profile [Time frame: 1, 3, 6 , 12 months after injection]
  • Left ventricular internal diameter end systole (LVIDs) [Time frame: 1, 3, 6 , 12 months after injection]
  • Left ventricular internal diameter end diastole (LVIDd) [Time frame: 1, 3, 6 , 12 months after injection]
  • Left ventricular end-systolic volume (LVESV) [Time frame: 6 , 12 months after injection]
  • Left ventricular end-diastolic volume (LVEDV) [Time frame: 6 , 12 months after injection]
  • NT-proBNP [Time frame: 1, 3, 6 , 12 months after injection]
  • 6 minutes walk test (6MWT) [Time frame: 1, 3, 6 , 12 months after injection]
  • assessment of heart failure symptom [Time frame: 1, 3, 6, 12 months after injection]
  • Incidence of major adverse cardiovascular events (MACE) [Time frame: 1, 3, 6, 12 months after injection]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Single blind
Primary purpose
Treatment

Study locations

China · 1 center
  • Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT06902896 · YAN2024-1210

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗