EXCELLENT (EXpanded CELL ENdocardiac Transplantation) (EXCELLENT)

• ClinicalTrials.gov Identifier: NCT02669810
• Recruitment Status: Completed
• First Posted: February 1, 2016
• Last Update Posted: April 26, 2024
• Sponsor: CellProthera
• Information provided by (Responsible Party): CellProthera

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction	Drug: PROTHERACYTES; Drug: Standard Treatment for CHF post AMI	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: EXpanded CELL ENdocardiac Transplantation (EXCELLENT)
• Actual Study Start Date: September 25, 2015
• Actual Primary Completion Date: March 15, 2024
• Actual Study Completion Date: March 15, 2024

Arms and Interventions

Arm	Intervention/treatment
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
Active Comparator: Standard of Care; Patients will be treated as standard treatment for CHF post - AMI.	Drug: Standard Treatment for CHF post AMI

Outcome Measures

Primary Outcome Measures :

1. Major Adverse Cardiac Events (MACE) [ Time Frame: From randomization up to 6 months ]
   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

Secondary Outcome Measures :

1. Left Ventricle End Systolic Volume index (LVESVi) [ Time Frame: From Baseline up to 6 months ]

   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)
2. Viability improvement of the infarcted segment(s) [ Time Frame: From Baseline up to 6 months ]
   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.
3. Other secondary outcomes measures [ Time Frame: From Baseline up to 6 months ]
   Cardiac event free survival; Quality of life via SF36 scale

Other Outcome Measures:

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

Eligibility Criteria

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

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)

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.

Contacts and Locations

Locations

France

CHU BESANCON Hopital Jean Minjoz 3 Boulevard A.Fleming

Besançon, France, 25030

CHU DIJON Hôpital François Mitterrand 14 rue Gaffarel

Dijon, France, 21079

CHU de Grenoble

Grenoble, France

Institut Jacques Cartier

Massy, France

CHU Montpellier Arnaud-De-Villeneuve

Montpellier, France

GHRMSA

Mulhouse, France, 68100

Hôpital Haut Levèque

Pessac, France

Hôpital de Rangueil

Toulouse, France

United Kingdom

Ninewells Hospital & Medical School

Dundee, United Kingdom, B15 2GW

BIRMINGHAM, Queen Elizabeth Hospital ,Mindelsohn Way,

Edgbaston, United Kingdom, B15 2GW

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, EC1A 7BE

Sponsors and Collaborators

CellProthera

More Information

• Responsible Party: CellProthera
• ClinicalTrials.gov Identifier: NCT02669810
• Other Study ID Numbers: EudraCT 2014-001476-63
• First Posted: February 1, 2016
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases