A Phase I-IIa Trial on the Safety and Preliminary Effectiveness of Intramyocardial Injection of Allogeneic Cardiac Atrial Stem Cells for the Treatment of Heart Failure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CASC8

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-08-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

To evaluate the safety of per operative direct intramyocardial injection of allogeneic cardiac atrial appendage stem cells by determining Major Adverse Cardiac Events (MACE):
• Death and cause of death
• Re-admissions and cause of re-admission
• Myocardial infarction
• Tumour formation

Secondary objectives 2

1. To evaluate the safety of a specific surgical intervention with the use of allogeneic cardiac atrial appendage stem cells by determining non-MACE
2. To evaluate the efficacy of allogeneic cardiac atrial appendage stem cells administered by intramyocardial injection

Conditions and MedDRA coding

Heart Failure

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. - Any subject meeting all of the following inclusion criteria and verified by the Investigator during the screening period, i.e. at visits 1 and 2, will be considered acceptable for trial inclusion.
2. - Subject has understood and accepted to participate in the trial according to all trial procedures by signing the approved informed consent.
3. - Male or female subjects aged >18
4. - Presence of a documented myocardial infarction due to coronary artery atherosclerotic disease as evidenced by conventional ECG criteria
5. - An area of regional dysfunction, i.e. hypokinetic, akinetic or dyskinetic as assessed by echocardiography, ventriculography or MRI-scan.
6. - The evidence of scar tissue on MRI-scan as shown by (gadolinium) delayed enhancement.
7. - Left ventricular ejection fraction of ≥ 25% and ≤ 45% as determined by clinically indicated assessment of cardiac function (echocardiogram, X-ray, ventriculography, CT and/or MRI).
8. - Need for revascularization including the infarcted area by CABG. If no further revascularization is clinically indicated at the time the patient is assessed for participation in the clinical trial this will be determined by a cardiologist who is not an investigator. No further revascularization may be indicated by no arteries with significant stenosis, adequate result of prior PCI, location and extent of any stenosis not suitable for angioplasty.
9. - Ability to provide informed consent and follow-up with protocol procedures. Subject is, in the Investigator’s opinion, psychosocially, mentally and physically able to fully comply with this protocol, including the postoperative regimen and follow-up visits.
10. - Safety laboratory test results and pre-surgery serology are clinically acceptable to undergo surgery at Visits 1 and 2.
11. - Women of childbearing potential (WOCBP) including peri-menopausal women who have had a menstrual period within 1 year have to have a negative pregnancy test. Results must be available and negative for the subject to be entered in the trial.
12. - WOCBP have to use an effective method of birth control 2 months prior to trial entry or to surgical intervention date and throughout the trial duration (defined as a method which results in a failure rate of less than 1% per year).

Exclusion criteria 21

1. - Non-cardiovascular disease with life expectancy of less than 1 year
2. - Contra indications to MRI, including prior (MRI non-compatible) ICD placement, estimated glomerular filtration rate less than 50 ml per minute, known reaction to gadolinium, claustrophobia, MRI non-compatible pacemaker and cochlear implant. History of possible presence of ferromagnetic material including programmable shunt, penile prosthesis, intrauterine device, bullets, tattoos, artificial limb, blood vessel coil and tissue expander may require special screening.
3. - History of cardiac tumour or cardiac tumour demonstrated on MRI.
4. - Patients in whom revascularisation of the infarct-related artery is technically not possible
5. - Current alcohol or drug abuse because of anticipated difficulty in complying with protocol related procedures.
6. - Abnormal liver function (GPT > 3 times the upper reference range) and/or haematology (hematocrit < 25%, WBC < 3000, platelets < 100000) studies without a reversible, identifiable cause.
7. - Subject has compromised renal function as reflected by a serum creatinine level >3.0 mg/dL (>0.265 mmol/l) or is currently on dialysis.
8. - Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.
9. - Symptomatic ventricular tachyarrhythmia complicating the index infarction.
10. - NYHA class IV congestive heart failure.
11. - Evidence of tumour on screening chest/abdominal/pelvic examination.
12. - Subject is on a transplant list or having received a solid organ transplant at any point in the past.
13. - Pregnant or breast-feeding woman.
14. - Involved in or planning to engage in litigation related health problems.
15. - Subject is a prisoner (incarcerated).
16. - Subject previously received a cellular therapy (at any point in time).
17. - Subject was exposed to therapy for a malignancy or pre-malignant entity, and not confirmed disease-free for 5 years or more.
18. - Any clinically relevant chronic disease associated with renal or hepatic insufficiency or any chronic disease of such severity that surgery could be detrimental to the survival of the subject.
19. - Any other illness which might reduce life expectancy to less than 2 years from screening.
20. - Subject is on chronic immunosuppressive therapy (immunosuppressants or immunotherapy) due to inflammatory or systemic disease.
21. - Subject has a history of any autoimmune disease such as systemic lupus erythematosus, Addison's disease, active Crohn's disease, or rheumatoid arthritis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. MACE : • Death and cause of death
2. MACE : • Re-admissions and cause of re-admission
3. MACE : • Myocardial infarction
4. MACE : • Tumour formation

Secondary endpoints 8

1. safety - non-MACE : • worsening of heart failure events defined as requiring unscheduled treatment for signs and symptoms of heart failure in an urgent outpatient setting or requiring hospital admission
2. safety - non - MACE: • aborted sudden death events, defined as resuscitated sudden death or appropriate Automatic Implantable Cardioverter Defibrillator (AICD) therapy for severe ventricular tachyarrhythmias
3. safety - non-MACE : • change in Six-Minute Walk Test from pre-procedure
4. safety - non-safety : • total days alive out of hospital
5. safety - non - MACE : • changes in NYHA class from pre-procedure and proportion of patients with improved NYHA classification
6. efficacy : • global and regional left ventricular function
7. efficacy : • ventricular dimensions
8. efficacy : • measurements of infarct size

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CASC8

Sponsor organisation

CASC8

Address

Dijlestraat 3

City

KEERBERGEN

Postcode

3140

Country

Belgium

Scientific contact point

Organisation

CASC8

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

CASC8

Contact name

Clinical Trial Information Desk

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

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

Documents 11 files

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

Application history

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