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

Plain English Summary

Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy is a Phase 1 clinical trial sponsored by Second Affiliated Hospital, School of Medicine, Zhejiang University studying Dilated Cardiomyopathy (DCM), Heart Failure. This trial tests a new type of cell therapy called CAR-DC, which is designed to reduce inflammation in the heart. It is for adults with advanced dilated cardiomyopathy (a condition where the heart muscle is weakened and enlarged) who have not responded well to standard treatments. Participants will receive the experimental cell therapy through an IV infusion, and will be closely monitored for side effects and changes in heart function. Current treatment options for end-stage dilated cardiomyopathy are limited and often involve heart transplantation or mechanical support devices. The trial aims to enroll 8 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-75 with a diagnosis of dilated cardiomyopathy and advanced heart failure symptoms (NYHA class IIIB-IV). Patients must have a weakened heart pump (ejection fraction <35%) despite at least 3 months of optimized medication. Individuals with recent heart attacks, strokes, certain heart conditions, active infections, severe kidney or liver problems, or those who are pregnant cannot participate. This trial is studying Dilated Cardiomyopathy (DCM), Heart Failure, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes will measure how safe the treatment is by looking for serious side effects and toxicity within the first two weeks after receiving the therapy. The specific primary outcome measures are: The proportion of subjects with Dose-limiting toxicity (DLT) (in 14 days after injection); Incidence of treatment-emergent adverse events (TEAEs) (in 14 days after injection). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial aims to provide a new treatment option for patients with end-stage dilated cardiomyopathy, a condition with limited effective therapies. This research targets Dilated Cardiomyopathy (DCM), Heart Failure, where improved treatment options are needed.

Investor Insight

This early-phase trial explores a novel cell therapy for a significant unmet need in heart failure, potentially opening a new therapeutic avenue if successful. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of this experimental cell therapy compared to your current treatment options. Participation involves receiving the therapy via IV infusion and regular follow-up appointments for monitoring. You will need to undergo blood tests and heart function assessments throughout the trial. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 8 participants

Interventions

• BIOLOGICAL: FAP immunosuppressive CAR-DC — Each subject receive FAP immunosuppressive CAR-DC by intravenous infusion

Primary Outcomes

• The proportion of subjects with Dose-limiting toxicity (DLT) (in 14 days after injection)
• Incidence of treatment-emergent adverse events (TEAEs) (in 14 days after injection)

Secondary Outcomes

• Left ventricular ejection fraction (LVEF) (1, 3, 6 months after injection)
• Left ventricular ejection fraction (LVEF) (6 months after injection)
• Enhanced volume (volume%) (6 months after injection)
• INTERMACS Profile (1, 3, 6 months after injection)
• Left ventricular internal diameter end systole (LVIDs) (1, 3, 6 months after injection)

Full 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.

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Dilated Cardiomyopathy
• Heart Failure
• Cardiomyopathy
• Heart Failure with Reduced Ejection Fraction (HFrEF)
• End-stage Heart Disease
• Cardiac Dysfunction
• Myocardial Disease
• Congestive Heart Failure
• Arrhythmia
• Pulmonary Hypertension

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