Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure (BioVAT-HF)

University Medical Center Goettingen

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Heart Failure

Treatments: Biological: EHM implantation

Study type: Interventional

Funder types: Other

Identifiers

NCT04396899

02289

Details and patient eligibility

About

The BioVAT-HF trial will test the hypothesis that cardiomyocyte implantation via engineered heart muscle (EHM), the proposed investigational medicinal product (IMP; designated "Biological Ventricular Assist Tissue" or BioVAT), results in sustainable remuscularization and biological enhancement of myocardial performance in the failing heart. EHM are constructed from defined mixtures of induced pluripotent stem cell (iPSC)-derived cardiomyocytes and stromal cells in a bovine collagen type I hydrogel. Comprehensive preclinical testing confirmed the rationale for the clinical translation of the myocardial remuscularization strategy by EHM implantation. The patient target population for EHM therapy is patients suffering from advanced heart failure with reduced ejection fraction (HFrEF; EF: ≤35%) and no realistic option for heart transplantation.

Enrollment: 53 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. HFrEF (EF ≤ 35%) as assessed by high-resolution echocardiography or MRI
2. No realistic chance or not eligible for heart transplantation
3. At least one hypo- or dyskinetic segment to demark the implant target area
4. Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or open-chest surgery (for RV applications) for a clinically indicated intervention on the LV (e.g., coronary bypass surgery, valve repair) with concomitant RV dysfunction, diagnosed using the Tricuspid Annular Plane Systolic Excursion (TAPSE) index <16 mm (Rudski et al. 2010).
5. 18-80 years of age
6. Previous implantation of an ICD or CRT-D with event recorder
7. New York Heart Association (NYHA) Class III or IV under optimal medical therapy
8. Willingness and ability to give written informed consent
9. Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.

Exclusion criteria

1. Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
2. Alloimmunisation against EHM implant cells
3. Hypertrophic cardiomyopathy (HCM)
4. Terminal kidney failure (stage 4; GFR <30 ml/min)
5. Terminal liver failure
6. Autoimmune disease
7. History of stroke
8. Reduced life expectancy in the short term due to non-cardiac disease
9. Simultaneous participation in another interventional trial
10. Pregnant or breastfeeding females
11. Known or suspected alcohol and/or drug abuse

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 1 patient group

EHM Implantation

Other group

Description:

All patients will receive EHM implant

Treatment:

Biological: EHM implantation