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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

29 Jan 2021 → ongoing

Decision date (initial)

2024-08-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515708-38-01

EudraCT number

2019-000885-39

ClinicalTrials.gov

NCT04396899

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Primary objectiv is to assess safety and efficacy of Engineered Human Myocardium (EHM) in patients with terminal heart failure (HFrEF EF ≤35%) with or without RV dysfunction (TAPSE <16 mm)

Secondary objectives 1

1. Secondary objective is to assess effects of EHM-grafts on disease-specific events and symptoms

Conditions and MedDRA coding

Heart failure

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Heart failure with reduced ejection fraction (HFrEF with EF ≤ 35%) as assessed by high-resolution echocardiography and MRI or CT.
2. At least one hypo- or dyskinetic segment to demark the implant target area.
3. 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, 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).
4. 18-80 years of age
5. Previous implantation of an ICD or CRT-D with event recorder
6. New York Heart Association (NYHA) Class III or IV under optimal medical therapy
7. Willingness and ability to give written informed consent
8. Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.

Exclusion criteria 12

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A (Dose Escalation steps): Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (based on a comparison of data obtained during visit 2 and visit 7)
2. Part B: Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within the whole study duration
3. Evidence for structural and functional muscular augmentation of target myocardium determined as enhanced target heart wall thickness (HWT) and thickening fraction (HWTF)

Secondary endpoints 10

1. Frequency of major adverse cardiac events (MACE; non-fatal myocardial infarction, non-fatal stroke and cardiovascular death)
2. Frequency and severity of arrhythmic events
3. Incidence of immune rejection (allograft DNA, CK/CK-MB, cTnT. DSA)
4. Incidence of mechanical perturbation of ventricular function by EHM graft
5. Recurrent HF hospitalizations
6. Left ventricular ejection fraction (EF)
7. Change in heart failure medication
8. Functional status in patients as determined by cardiopulmonary stress testing (VO2max), six-minute walk test (6MWT), and hand-grip strength measurements
9. Patient reported outcomes assessed by NYHA classification, quality of life score (KCCQ, EQ-5D, QoL-VAD), and study adherence motivation (PHQ-9, HAF-17, ESSI, LOT-R, ULS-8, medication adherence, Trust/Mistrust in medical staff)
10. All-cause and cardiovascular mortality

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Florian Walker

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Florian Walker

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications