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

Heart Failure Clinical Trial

— BioVAT-HF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04396899
• Other study ID #: 02289
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 3, 2020
• Est. completion date: October 2024

Study information

• Verified date: March 2023
• Source: University Medical Center Goettingen
• Contact: Wolfram-Hubertus Zimmermann, Prof.
• Phone: +49 551 / 3965781
• Email: sekretariat.pharma[@]med.uni-goettingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: October 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Biological:
• EHM implantation
Implantation of EHM on dysfunctional left or right ventricular myocardium in patients with HFrEF (EF <35%).

Locations

Country	Name	City	State
Germany	Herz- und Diabeteszentrum Nordrhein-Westfalen	Bad Oeynhausen	North Rhine-Westphalia
Germany	University Medical Center Göttingen	Göttingen	Lower Saxony
Germany	University Medical Center Schleswig-Holstein	Lübeck	Schleswig-Holstein

Sponsors (4)

Lead Sponsor	Collaborator
University Medical Center Goettingen	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Repairon GmbH, University Medical Center Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Target heart wall thickness	Target heart wall thickness (HWT) as determined by high resolution echocardiography and/or CINE-mode MRI (17-segment model). Primary efficacy analyses are based on the changes in HWT between baseline and 2 weeks, 1 month, 3 months, 6 months and 12 months after implantation. To test for a time effect a one-way Repeated Measures ANOVA will be performed for the primary endpoint. In case of detecting a time effect this is followed by Dunnett-type pairwise comparisons to baseline using paired t-Tests. Due to the explorative character of the efficacy analysis testing will be performed at a 10% two-sided significance level. Mean differences will be reported along with 90% confidence intervals.	12 months
Primary	Heart wall thickening fraction	Heart wall thickening fraction (HWTF) as determined by high resolution echocardiography and/or CINE-mode MRI (17-segment model). Primary efficacy analyses are based on the changes in HWTF between baseline and 2 weeks, 1 month, 3 months, 6 months and 12 months after implantation. To test for a time effect a one-way Repeated Measures ANOVA will be performed for the primary endpoint. In case of detecting a time effect this is followed by Dunnett-type pairwise comparisons to baseline using paired t-Tests. Due to the explorative character of the efficacy analysis testing will be performed at a 10% two-sided significance level. Mean differences will be reported along with 90% confidence intervals.	12 months