EXCELLENT (EXpanded CELL ENdocardiac Transplantation) (EXCELLENT)

EXpanded CELL ENdocardiac Transplantation (EXCELLENT)

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.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: PROTHERACYTES; Drug: Standard Treatment for CHF post AMI

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • CHU BESANCON Hopital Jean Minjoz 3 Boulevard A.Fleming
  • Dijon, France, 21079
    • CHU DIJON Hôpital François Mitterrand 14 rue Gaffarel
  • Grenoble, France
    • CHU de Grenoble
  • Massy, France
    • Institut Jacques Cartier
  • Montpellier, France
    • CHU Montpellier Arnaud-De-Villeneuve
  • Mulhouse, France, 68100
    • GHRMSA
  • Pessac, France
    • Hopital Haut Leveque
  • Toulouse, France
    • Hopital de Rangueil
• United Kingdom
  • Dundee, United Kingdom, B15 2GW
    • Ninewells Hospital & Medical School
  • Edgbaston, United Kingdom, B15 2GW
    • BIRMINGHAM, Queen Elizabeth Hospital ,Mindelsohn Way,
  • Edinburgh, United Kingdom
    • University of Edinburgh
  • Leeds, United Kingdom
    • Leeds University & Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, EC1A 7BE
    • Saint Bartholomew's Hospital W Smithfield,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Non-inclusion criteria

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Patients will be treated as standard treatment for CHF post - AMI.	Drug: Standard Treatment for CHF post AMI
Experimental: 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	Drug: PROTHERACYTES; ProtheraCytes endocardiac injections performed with the HELIX and Morph catheters; Drug: Standard Treatment for CHF post AMI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiac Events (MACE)	The primary endpoint is the incidence of Major Adverse Cardiac Events (MACE), which have been adjudicated and confirmed to be a MACE by an independent and blinded Clinical Events Committee (CEC) from randomization	From randomization up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricle End Systolic Volume index (LVESVi)	Improvement of LVESVi will be assessed by comparing cMRI at baseline, 3 and 6 months. The left ventricular volumes will be indexed to body surface area. cMRI will also assess other parameters such as: Left ventricular end diastolic volume index (ml/m²); Left ventricular ejection fraction (%); Left ventricular mass (g)	From Baseline up to 6 months
Viability improvement of the infarcted segment(s)	The viability assessment will be performed using cMRI and perfusion 99mTc SPECT (optional) respectively. A correlation assessment between LVESVi improvement and viability of the infarcted segment(s) will be statistically performed.	From Baseline up to 6 months
Other secondary outcomes measures	Cardiac event free survival; Quality of life via SF36 scale	From Baseline up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome measures	Incidence of adverse events in patient treated via the intracoronary route	From randomization up to 6 months
Exploratory outcome measures	Improvement of MACE, of LVESVi, viability of infarcted segments and other cMRI parameters in patient treated with intracoronary route	From randomization up to 6 months
Exploratory outcome measures	cMRI parameters related to microvascular obstruction (MVO) and myocardial perfusion in all patients	From Baseline up to 6 months

Collaborators and Investigators

• Sponsor: CellProthera

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2015
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): March 15, 2024

Study Registration Dates

• First Submitted: January 25, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimated): February 1, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: EudraCT 2014-001476-63