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

Primary Purpose

Heart Failure

Status
Recruiting
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
EHM implantation
Sponsored by
University Medical Center Goettingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Medical Center GöttingenRecruiting
  • Herz- und Diabeteszentrum Nordrhein-Westfalen
  • University Medical Center Schleswig-HolsteinRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

EHM Implantation

Arm Description

All patients will receive EHM implant

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 11, 2020
Last Updated
March 23, 2023
Sponsor
University Medical Center Goettingen
Collaborators
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), University Medical Center Freiburg, Repairon GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT04396899
Brief Title
Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 3, 2020 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Goettingen
Collaborators
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), University Medical Center Freiburg, Repairon GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EHM Implantation
Arm Type
Other
Arm Description
All patients will receive EHM implant
Intervention Type
Biological
Intervention Name(s)
EHM implantation
Intervention Description
Implantation of EHM on dysfunctional left or right ventricular myocardium in patients with HFrEF (EF <35%).
Primary Outcome Measure Information:
Title
Target heart wall thickness
Description
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.
Time Frame
12 months
Title
Heart wall thickening fraction
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HFrEF (EF ≤ 35%) as assessed by high-resolution echocardiography or MRI No realistic chance or not eligible for heart transplantation At least one hypo- or dyskinetic segment to demark the implant target area 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). 18-80 years of age Previous implantation of an ICD or CRT-D with event recorder New York Heart Association (NYHA) Class III or IV under optimal medical therapy Willingness and ability to give written informed consent Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration. Exclusion Criteria: Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1) Alloimmunisation against EHM implant cells Hypertrophic cardiomyopathy (HCM) Terminal kidney failure (stage 4; GFR <30 ml/min) Terminal liver failure Autoimmune disease History of stroke Reduced life expectancy in the short term due to non-cardiac disease Simultaneous participation in another interventional trial Pregnant or breastfeeding females Known or suspected alcohol and/or drug abuse
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wolfram-Hubertus Zimmermann, Prof.
Phone
+49 551 / 3965781
Email
sekretariat.pharma@med.uni-goettingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Florian Walker, Dr.
Phone
+49 551 / 3960825
Email
biovat@med.uni-goettingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim Seidler, Prof.
Organizational Affiliation
University Medical Center Goettingen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wolfram-Hubertus Zimmermann, Prof.
Organizational Affiliation
University Medical Center Goettingen
Official's Role
Study Director
Facility Information:
Facility Name
University Medical Center Göttingen
City
Göttingen
State/Province
Lower Saxony
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tim Seidler, Prof.
Facility Name
Herz- und Diabeteszentrum Nordrhein-Westfalen
City
Bad Oeynhausen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
32545
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Gummert, Prof.
Facility Name
University Medical Center Schleswig-Holstein
City
Lübeck
State/Province
Schleswig-Holstein
ZIP/Postal Code
23562
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan Ensminger, Prof.

12. IPD Sharing Statement

Learn more about this trial

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

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