EXCELLENT (EXpanded CELL ENdocardiac Transplantation)

NCT ID: NCT02669810

Last Updated: 2024-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-25
• Study Completion Date: 2024-03-15

Brief Summary

A multicentric controlled phase I / IIb study evaluating the safety and the efficacy of in vitro expanded peripheral blood CD34+ stem cells output by the StemXpand® Automated Process, and injected in patients with an acute myocardial infarction and a LVEF remaining below 50% versus standard of care.

Detailed Description

The main purpose of this phase I/IIb is to evaluate the safety, the tolerance and the first efficacy trends of intracardiac injection of ProtheraCytes (autologous PB-CD34+ Stem Cells after automated ex-vivo expansion with the StemXpand machine) in patients with an acute myocardial infarction and decreased ejection fraction. ProtheraCytes will be reinjected using a dedicated catheter , thus avoiding open chest surgery.

Conditions

Acute Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PROTHERACYTES

The interventional investigators will perform the ProtheraCytes® cardiac injections using a catheter introduced via the femoral route up to the left ventricle cavity for intraventricular injections (Helix/Biocardia).

Intracoronary injection will be possible with OTW catheter or microcatheter (UK only) if patient presents a contraindication to intramyocardial injection

Group Type: EXPERIMENTAL

PROTHERACYTES

Intervention Type: DRUG

ProtheraCytes endocardiac injections performed with the HELIX and Morph catheters

Standard Treatment for CHF post AMI

Intervention Type: DRUG

Standard of Care

Patients will be treated as standard treatment for CHF post - AMI.

Group Type: ACTIVE_COMPARATOR

Standard Treatment for CHF post AMI

Intervention Type: DRUG

Interventions

PROTHERACYTES

ProtheraCytes endocardiac injections performed with the HELIX and Morph catheters

Intervention Type: DRUG

Standard Treatment for CHF post AMI

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. LV main AMI with or without ST segment elevation and with a detection of rise of troponin with at least one value 70 times above the upper reference limit.

2. MI within 1 week after first symptoms. D0 = day of last stent implantation or; D0 = day of hospital presentation when no stent implanted.

3. Combination of LVEF < 50% and LV akinetic or dyskinetic segment(s) - by echography as per local practice

4. Age must be ≥ 18 and ≤ 85 years

5. Men and Non-pregnant non-lactating women who take efficacious contraceptive measures such as oral contraceptive medications or efficacious and permanent intra-uterine device (drug eluted or not) (IUD) or subcutaneous permanent contraceptive implants or menopaused women (at least 2 years confirmed menopause) or surgically sterilized women.

6. Having previously signed a written informed consent prior to any study-specific procedure

7. LVEF remaining < 50% assessed by cMRI at D8 (± 3)

8. Identification of LV segment(s) both non-viable (transmural scar extend >50%) and akinetic (no cardiac wall thickening during systole) or dyskinetic (cardiac wall thickening in the wrong orientation during systole) by cMRI at D8 (± 3)

1. History of CABG surgery

2. History of former significant mitral valve replacement surgery or heart transplantation.

3. History of severe valve disease: mitral, aortic stenosis / insufficiency.

4. History of non-ischemic dilated cardiomyopathy due to valvular dysfunction, mitral regurgitation, tachycardia, or myocarditis.

5. Aortic stenosis as determined as valve area less than 1 cm2 that prohibits catheter access to LV.

6. Presence of a prosthetic / mechanical aortic or mitral valve or heart constrictive device.

7. Sepsis.

8. Endocarditis.

9. Infectious pericarditis;

10. Pericardial tamponade.

11. Left Ventricular Thrombus detected at Echo or MRI

12. Severe peripheral vascular disease precluding femoral artery access as determined at the time of original catheterization.

13. Any condition leading to contraindicated or unexploitable cMRI.

14. History of metallic foreign body in their eye

15. Former or current aortic dissection

16. Previous G-CSF or other hematopoietic growth factor administration.

17. Hepatic failure, history of liver cirrhosis or hepatic severe impairment.

18. Constitutional or acquired coagulopathy

19. Treated chronic renal failure, haemodialysis or renal severe impairment (creatinine clearance < 30 ml/min).

20. Prior or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer or previous cancer in complete response without any treatment in the last 5 years.

21. History of prior mediastinal radiation exposure.

22. Serious underlying medical condition at the investigator's discretion, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, active autoimmune disease, Amyotrophic Lateral Sclerosis, Systemic Lupus, Multiple Sclerosis).

23. Chronic immunomodulatory or cytotoxic drug treatment intake.

24. Active bleeding or major surgery within 1 month.

25. History or current Human immunodeficiency HIV1-2, HTLV1, HTLV2 (according to 2006/17/EC).

26. Current Active Hepatitis B (according to 2006/17/EC) based on the decision of the biologist or/and the PI.

27. History or current Hepatitis C (according to 2006/17/EC).

28. Syphilis (according to 2006/17/EC) based on the decision of the biologist or/and the P.

29. Active participation in any other clinical trials.

30. Current or recent treatment (within two months) with another investigational drug or procedure.

31. Any other co-existing conditions that will preclude participation in the study or compromise ability to give informed consent.

32. Impairment of cognitive function. If patient is 75-85 years old (included), score < 24 at Mini Mental State Examination (MMSE)

33. History of Splenomegaly;

34. History of Phenylketonuria;

35. History of iron-Dextran allergy;

36. History of murine protein allergy.

37. Diagnosis of Takotsubo

Discontinuation criteria

1. Inadequate bone marrow function: patient at risk to have Haemoglobin < 10 g/dL and Platelet count < 100 x 109 /L at the time of blood harvest

2. Blood transfusion within the previous 3 days before the first G-CSF injection

3. Cardiogenic shock: requirement of i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump) initiated 24 hours before screening cMRI.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CellProthera

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU BESANCON Hopital Jean Minjoz 3 Boulevard A.Fleming

Besançon, , France

CHU DIJON Hôpital François Mitterrand 14 rue Gaffarel

Dijon, , France

CHU de Grenoble

Grenoble, , France

Institut Jacques Cartier

Massy, , France

CHU Montpellier Arnaud-De-Villeneuve

Montpellier, , France

GHRMSA

Mulhouse, , France

Hôpital Haut Levèque

Pessac, , France

Hôpital de Rangueil

Toulouse, , France

Ninewells Hospital & Medical School

Dundee, , United Kingdom

BIRMINGHAM, Queen Elizabeth Hospital ,Mindelsohn Way,

Edgbaston, , United Kingdom

University of Edinburgh

Edinburgh, , United Kingdom

Leeds University & Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Saint Bartholomew's Hospital W Smithfield,

London, , United Kingdom

Countries

France; United Kingdom

References

Aries A, Vignon C, Zanetti C, Goubaud A, Cormier A, Diederichs A, Lahlil R, Henon P, Garitaonandia I. Development of a potency assay for CD34+ cell-based therapy. Sci Rep. 2023 Nov 11;13(1):19665. doi: 10.1038/s41598-023-47079-8.

Reference Type: DERIVED

PMID: 37952030 (View on PubMed)

Other Identifiers

EudraCT 2014-001476-63

Identifier Type: -

Identifier Source: org_study_id