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

• ClinicalTrials.gov Identifier: NCT04396899
• Recruitment Status: Recruiting
• First Posted: May 21, 2020
• Last Update Posted: March 27, 2023
• Sponsor: University Medical Center Goettingen
• Collaborators: Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK); University Medical Center Freiburg; Repairon GmbH
• Information provided by (Responsible Party): Karsten Gavenis, University Medical Center Goettingen

Tracking Information

• First Submitted Date: May 11, 2020
• First Posted Date: May 21, 2020
• Last Update Posted Date: March 27, 2023
• Actual Study Start Date: February 3, 2020
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 15, 2020)

• Target heart wall thickness [ Time Frame: 12 months ]
  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.
• Heart wall thickening fraction [ Time Frame: 12 months ]
  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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
• Official Title: Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

Biological: EHM implantation

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

Study Arms

EHM Implantation

All patients will receive EHM implant

Intervention: Biological: EHM implantation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 15, 2020): 53
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wolfram-Hubertus Zimmermann, Prof.; +49 551 / 3965781; sekretariat.pharma@med.uni-goettingen.de

Contact: Florian Walker, Dr.; +49 551 / 3960825; biovat@med.uni-goettingen.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04396899
• Other Study ID Numbers: 02289
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Karsten Gavenis, University Medical Center Goettingen
• Original Responsible Party: Karsten Gavenis, University Medical Center Goettingen, on behalf of Principal Investgator Prof. Zimmermann
• Current Study Sponsor: University Medical Center Goettingen
• Original Study Sponsor: Same as current

Collaborators

• Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)
• University Medical Center Freiburg
• Repairon GmbH

Investigators

• Principal Investigator: Tim Seidler, Prof.; University Medical Center Goettingen
• Study Director: Wolfram-Hubertus Zimmermann, Prof.; University Medical Center Goettingen

• PRS Account: University Medical Center Goettingen
• Verification Date: March 2023