EXpanded CELL ENdocardiac Transplantation (EXCELLENT) (EXCELLENT)

• Sponsor: CellProthera
• Information provided by (Responsible Party): CellProthera

Study Description

Brief Summary:

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 a De Novo acute myocardial infarction and decreased ejection fraction. ProtheraCytes will be reinjected using a dedicated catheter pushed through the femoral artery up to the left ventricle, thus avoiding open chest surgery.

Condition or disease	Intervention/treatment	Phase
Acute Myocardial Infarction	Drug: PROTHERACYTES; Device: Standard of Care (Percutaneous Transluminal Coronary Angioplasty and stent(s) implantation)	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	44 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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 Left Ventricle Ejection Fraction (LVEF) Remaining Below or Equal to 45% After PTCA and Stent(s) Implantation Versus Standard of Care.
Actual Study Start Date :	September 25, 2015
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: PROTHERACYTES; The interventional investigators will perform the ProtheraCytes® endocardiac injections using the HELIX® catheter introduced via the femoral route up to the left ventricle cavity.	Drug: PROTHERACYTES; ProtheraCytes endocardiac injections performed with the HELIX and Morph catheters
Active Comparator: Standard of Care; Patients will undergo standard of care procedure (PTCA Percutaneous Transluminal Coronary Angioplasty and stent(s) implantations)	Device: Standard of Care (Percutaneous Transluminal Coronary Angioplasty and stent(s) implantation)

Outcome Measures

Primary Outcome Measures :

1. Proportion of adverse events (including MACE), defined as the proportion of subjects with at least one adverse event from baseline until 6 months. [ Time Frame: 6 Months ]

Secondary Outcome Measures :

1. Improvement of the Left Ventricle End Systolic Volume index will be assessed by cMRI. The left ventricular volumes will be indexed to body surface area. [ Time Frame: 6 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• De Novo Anterior wall AMI with or without ST segment elevation and with a detection of rise and/or fall of cardiac biomarker values (troponin) with at least one value above the 99th percentile of the upper reference limit.
• LVEF ≤ 45% after stent(s) implantation: Combination of a LVEF ≤ 45 % and of anterior akinetic segment(s) - by echography at Day 2 after stent(s) mplantations
• Age must be ≥ 18 and ≤ 75 years
• 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 a 2 years confirmed menopause) or surgically sterilized women.
• Having previously signed a written informed consent prior to any study- specific procedures.
• LVEF remaining ≤ 45% assessed by cMRI at Day 7 +/- 2 days after stent(s) implantation.
• Identification of anterior akinetic segment(s) of interest assessed by cMRI at Day 7 +/- 2 days after stent(s) implantation.
• Identification of non-viability of anterior segment(s) of interest assessed by perfusion 99mTc SPECT uptake at a day between Day 7 +/- 2 days and Day 10 +/- 2 days after stent(s) implantation.

Exclusion Criteria:

• Absence of stent(s) implantation
• Previous and known symptomatic CHF, from class II to IV (included)
• History of CABG surgery
• History of former significant mitral valve replacement surgery or heart transplantation.
• Severe valve disease: mitral, aortic stenosis / insufficiency.
• Diagnosis of non-ischemic dilated cardiomyopathy due to valvular dysfunction, mitral regurgitation, tachycardia, or myocarditis
• Aortic stenosis as determined as valve area less than 1 cm2 that prohibits.catheter access to LV
• Presence of a prosthetic / mechanical aortic or mitral valve or heart constrictive device.
• Documented presence of a known LV thrombus
• Sepsis
• Endocarditis
• Infectious pericarditis
• Pericardial tamponade
• Left ventricular aneurysm, collagen tissue disease
• Severe peripheral vascular disease precluding femoral artery access as determined at the time of original catheterization.
• Pacemaker, implantable cardiac defibrillator, and intra-cerebral aneurysm clips.
• History of metallic foreign body in their eye
• Severe claustrophobia
• Former or current aortic dissection
• Inadequate bone marrow function: Haemoglobin < 10 g/dL and Platelet count < 100 x 109 / L
• Previous G-CSF or other Hematopoietic Growth Factor administrations.
• Blood transfusion(s) within the previous 4 weeks (to exclude the potential of non-autologous ACPs (Angiogenic Cells Precursors) in the harvested blood).
• Hepatic failure or history of liver cirrhosis or hepatic severe impairment.
• Constitutional or acquired coagulopathy
• Treated chronic renal failure, or haemodialysis or renal severe impairment (creatinine clearance < 30ml/min).
• 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.
• History of prior mediastinal radiation exposure
• Serious underlying medical conditions 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).
• Chronic immunomudulatory or cytotoxic drug treatment intake.
• Active bleeding or major surgery within 1 month.
• Human immunodeficiency HIV1-2, HTLV1, HTLV2 (according to 2006/17/EC)
• Hepatitis B (without prior vaccination) and C (according to 2006/17/EC)
• Syphilis (according to 2006/17/EC)
• Chronic Obstructive Pulmonary Disease.
• Active participation in any other clinical trials
• Current or recent treatment (within the 60 days period before PTCA and stent(s) implantation) with another investigational drug or procedure).
• Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent.
• Requirement of i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump) between Day 7 +/- 2 days and Day 10 +/- 2 days after stent(s) implantation.
• Splenomegaly
• Phenylacetonuria
• History of iron-Dextran allergy
• History of murin protein allergy

Contacts and Locations

Contacts

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Contact: Anthony Criquet, MD		acriquet@cellprothera.com

Locations

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France
CHU de Grenoble	Recruiting
Grenoble, France
Contact: Gérald Vanzetto, MD, PhD
Institut Jacques Cartier	Not yet recruiting
Massy, France
Contact: Thierry Lefèvre, MD
CHU Montpellier Arnaud-De-Villeneuve	Recruiting
Montpellier, France
Contact: François Roubille, MD
Hôpital Haut Levèque	Recruiting
Pessac, France
Contact: Lionel Leroux, MD
Hôpital de Rangueil	Recruiting
Toulouse, France
Contact: Jérôme Roncalli, MD,PhD
Principal Investigator: Jérôme Roncalli, MD, PhD
United Kingdom
University of Edinburgh	Recruiting
Edinburgh, United Kingdom
Contact: David New, MD PhD
Leeds University & Leeds Teaching Hospitals NHS Trust	Recruiting
Leeds, United Kingdom
Contact: John Greenwood, MD PhD

Sponsors and Collaborators

CellProthera

Investigators

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Study Director:	Anthony Criquet, MD	CellProthera

More Information

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Responsible Party:	CellProthera
ClinicalTrials.gov Identifier:	NCT02669810 History of Changes
Other Study ID Numbers:	EudraCT 2014-001476-63
First Posted:	February 1, 2016
Last Update Posted:	November 14, 2017
Last Verified:	November 2017

Additional relevant MeSH terms:

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