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

Plain English Summary

Safety and Efficacy of Second Infusion 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 second dose of a special cell therapy (CAR-DC) to see if it's safe and helps improve heart function in patients with severe heart failure. It is for adults with a specific type of severe heart failure (dilated cardiomyopathy) who have already had one dose of this therapy and their condition has worsened again. Participation involves receiving a second infusion of the therapy and regular check-ups to monitor safety and heart function. Alternative treatments may include heart transplant, mechanical support devices, or standard heart failure medications. The trial aims to enroll 5 participants.

Official Summary

This study aims to evaluate the safety and preliminary efficacy of a second administration of fibroblast activation protein (FAP)-targeted immunosuppressive chimeric antigen receptor dendritic cells (CAR-DC) in patients with end-stage dilated cardiomyopathy. Previous clinical research has shown that single-dose CAR-DC therapy is safe and may provide clinical benefit. However, some patients experience recurrent worsening of heart function after initial treatment. This study will assess whether a second CAR-DC infusion is safe and whether it can further improve cardiac function in this patient population.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 75 years old and have been diagnosed with dilated cardiomyopathy. You must have previously received one dose of this CAR-DC therapy and experienced a decline in heart function after initial improvement. You should have persistent heart failure symptoms, a weakened heart pumping ability (LVEF <35%), and be in NYHA class III-IV. You cannot join if you have severe kidney problems, liver issues, active infections, or are hemodynamically unstable (e.g., in shock). This trial is studying Dilated Cardiomyopathy (DCM), Heart Failure, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure how safe the therapy is by looking for serious side effects and toxicities within the first two weeks after the infusion. 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 addresses a critical need for advanced therapies in end-stage heart failure, where current options are limited and often involve major interventions like transplant. This research targets Dilated Cardiomyopathy (DCM), Heart Failure, where improved treatment options are needed.

Investor Insight

This early-phase trial signals potential innovation in treating advanced heart failure, a large and growing market, with a novel cell-based approach. 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 a second CAR-DC infusion compared to other treatment options. Be prepared for regular clinic visits for infusions and monitoring of your heart function and overall health. Understand that this is an experimental treatment, and its effectiveness and long-term safety are still being studied. The trial is being conducted at multiple sites. 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: 5 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:

* ≥18 years and ≤75 years of age, with a confirmed diagnosis of dilated cardiomyopathy.
* Patients who previously received a single infusion of immunosuppressive CAR-DC (iCDC) therapy and, at 6 months after the first treatment, failed to maintain improvement in cardiac function, with cardiac function declining to baseline levels prior to treatment. These patients should have persistent heart failure symptoms that cannot be adequately improved, with left ventricular ejection fraction (LVEF) \<35%, New York Heart Association (NYHA) functional class III-IV, and INTERMACS profile 3-6.
* Able to verbally confirm understanding of the risks, benefits, and alternative treatment options of the second administration of iCDC therapy, and willing to participate in the study. The participant or his/her legal representative must provide written informed consent prior to enrollment.
* Hematocrit \>30%, lymphocyte count \>0.5 × 10⁹/L, and platelet count \>60 × 10⁹/L.

Exclusion Criteria:

* Severe renal failure or requirement for renal dialysis, or serum creatinine \>2.5 mg/dL.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than 5.0 times the upper limit of normal (ULN), or total bilirubin \>3 mg/dL.
* Presence of active infections at screening, including: Active hepatitis B infection with hepatitis B virus DNA \>1000 copies/mL by PCR testing; Hepatitis C virus infection; Syphilis; Human immunodeficiency virus (HIV) infection; Uncontrolled systemic fungal, bacterial, viral, or other pathogenic infections.
* Severe hemodynamic instability (e.g., shock).
* Known contraindications to the investigational product or study-related procedures.

Frequently Asked Questions

Related Conditions

• Dilated Cardiomyopathy
• Heart Failure
• End-stage Heart Disease
• Cardiomyopathy
• Congestive Heart Failure
• Myocardial Disease
• Cardiac Dysfunction
• Arrhythmia
• Pulmonary Hypertension
• Renal Insufficiency

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