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

NCT04396899 | Recruiting Phase 1 DMC

• 1 other identifier: 02289
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (4)

• Adverse events

  Number of Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (Part A) and the whole study duration (Part B)

  12 months

• Heart target heart wall thickness

  Change of target heart wall thickness (TWTh in mm) Echo or cCT or cMRI

  12 months

• LV/RV-ejection fraction

  Change of LV/RV-ejection fraction (LV/RV-EF in %) Echo or cCT or cMRI

  12 months

• Patient reported outcome

  Patient reported outcome Change of KCCQ-23 OSS (Overall Summary Score)

  12 months

Secondary Outcomes (18)

• Major adverse cardiac events

  12 months

• Arrhythmic events

  12 months

• Immune rejection

  12 months

• Mechanical perturbation of ventricular function

  12 months

• Recurrent hospitalizations for heart failure

  12 months

Study Arms (1)

EHM Implantation

OTHER

All patients will receive EHM implant

Biological: EHM implantation

Interventions

EHM implantation BIOLOGICAL

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

EHM Implantation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic heart failure (NYHA II-IV) with reduced ejection fraction (HFrEF with LVEF ≤35%) as assessed by echocardiography.
• Patients on guideline-directed medical therapy
• NT-proBNP \>300 pg/mL for patients in sinus rhythm or \>900 pg/mL if in atrial fibrillation
• History of previous heart failure hospitalization in the past 12 months
• At least one hypo- or dyskinetic segment or dilated heart chamber to demark the implant target area
• (A) Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or (B) open-chest surgery (for RV applications) for a clinically indicated intervention on the LV (e.g., coronary bypass surgery, valve repair, mechanical circulatory support device implantation) with concomitant RV dysfunction, diagnosed using the Tricuspid Annular Plane Systolic Excursion (TAPSE) index \<16 mm (Rudski et al. 2010).
• years of age
• 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.

You may not qualify if:

• Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
• Contraindication to TachoSil® (e.g. hypersensitivity to human fibrinogen, human thrombin, horse collagen, human albumin, Riboflavin, Natriumchloride, Natriumcitrate, L-Arginin-Hydrochloride)
• Hypertrophic cardiomyopathy (HCM)
• Terminal kidney failure (stage 4; GFR \<30 ml/min) at the time of enrolment
• Terminal liver failure (Child-Pugh stage C; score \>10) at the time of enrolment
• History of disabling stroke
• Reduced life expectancy in the short term due to non-cardiac disease
• Any condition that excludes adherence to study protocol (in particular lack of adherence to prescribed medication)
• Simultaneous participation in another interventional trial
• Pregnant or breastfeeding females
• Known or suspected alcohol and/or drug abuse

Sponsors & Collaborators

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

Study Sites (3)

University Medical Center Göttingen

Göttingen, Lower Saxony, 37075, Germany

RECRUITING

Herz- und Diabeteszentrum Nordrhein-Westfalen

Bad Oeynhausen, North Rhine-Westphalia, 32545, Germany

NOT YET RECRUITING

University Medical Center Schleswig-Holstein

Lübeck, Schleswig-Holstein, 23562, Germany

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Tim Seidler, Prof.

  University Medical Center Goettingen

  PRINCIPAL INVESTIGATOR

• Wolfram-Hubertus Zimmermann, Prof.

  University Medical Center Goettingen

  STUDY DIRECTOR

Central Study Contacts

Wolfram-Hubertus Zimmermann, Prof.

CONTACT

+49 551 / 3965781; sekretariat.pharma@med.uni-goettingen.de

Florian Walker, Dr.

CONTACT

+49 551 / 3960825; biovat@med.uni-goettingen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: on behalf of Principal Investigator Prof. Seidler and Study Director Prof. Zimmermann

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 21, 2020
• Study Start: February 3, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

DE (3)