Clinical Trial Results:
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.
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Summary
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EudraCT number |
2014-001476-63 |
Trial protocol |
SI |
Global end of trial date |
15 Mar 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Feb 2026
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First version publication date |
25 Feb 2026
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2014-001476-63
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT02669810 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
VHP process: VHP590 (VHP2014137), VHP process: VHP677 (VHP2015065) | ||
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Sponsors
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Sponsor organisation name |
CellProthera
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Sponsor organisation address |
12 rue du Parc , Mulhouse, France, 68100
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Public contact |
CellProthera SAS, CELLPROTHERA S.A.S, +33 369719771, medical@cellprothera.com
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Scientific contact |
CellProthera SAS, CELLPROTHERA S.A.S, +33 369719771, medical@cellprothera.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Jun 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Mar 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Mar 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the incidence of blindly adjudicated major adverse cardiac events (MACE)
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Protection of trial subjects |
The investigator affirms and upholds the principle of the patient's right to privacy. The investigators shall comply with applicable privacy laws. The investigator must assure that the patient’s anonymity will be maintained and that the identities are protected from unauthorized parties. The investigator should maintain documents in strict confidence. On eCRFs and other documents, patients should not be identified by their names. All clinical and scientific data are collected under an identification code plus investigational centre number, and stored in the main clinical trial database. Individual-related data (the patient’s name and address) are linked to the code in a separate patient identification list field in the investigator site file, which is used only for identifying the patient and matching to the ProtheraCytes® batch and for sending Quality of Life questionnaires during the follow up period.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Feb 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 17
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Country: Number of subjects enrolled |
France: 60
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Worldwide total number of subjects |
77
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EEA total number of subjects |
60
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
46
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From 65 to 84 years |
31
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Screening echography and cMRI scheduled at D8 (±3) post AMI. A mini mental state examination (MMSE) must be performed for patients aged 75-85 years old. Persistent LVEF <50%, identification of LV Segments both non-viable, and akinetic/dyskinetic. Biological analyses and serology for the purpose of inclusion/non-inclusion criteri | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ProtheraCytes | |||||||||||||||||||||||||||||||||
Arm description |
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). | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
ProtheraCytes
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intracardiac use
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Dosage and administration details |
Dosage : CD34+ Cells Count : ≥ 0.76 x 107
Administration : The intraventricular injection will be performed using the Helical™ catheter introduced via the femoral route up to the left ventricle cavity. The administration of the 15 (fifteen)
injections – of 1 mL each – will be performed under loco-regional anaesthesia.
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Arm title
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Standard Of Care | |||||||||||||||||||||||||||||||||
Arm description |
Patients will be treated as standard treatment for Chronic Heart Failure post - AMI. | |||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
ProtheraCytes
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Reporting group description |
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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard Of Care
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Reporting group description |
Patients will be treated as standard treatment for Chronic Heart Failure post - AMI. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Per Protocol Safety Set (PPSS)
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who were randomized AND for patients randomized to the ProtheraCytes® arm – who received transendocardial injection of ProtheraCytes
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End points reporting groups
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Reporting group title |
ProtheraCytes
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Reporting group description |
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). | ||
Reporting group title |
Standard Of Care
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Reporting group description |
Patients will be treated as standard treatment for Chronic Heart Failure post - AMI. | ||
Subject analysis set title |
Per Protocol Safety Set (PPSS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All patients who were randomized AND for patients randomized to the ProtheraCytes® arm – who received transendocardial injection of ProtheraCytes
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End point title |
Incidence of Majors Cardiacs Events [1] | ||||||||||||
End point description |
Incidence of MACE which have been adjudicated and confirmed to be MACE by an independent and blinded CEC from randomization up to 6 months in both treatments arms.
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End point type |
Primary
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End point timeframe |
Randomization up to 6 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No-comparative study : This proportion will be given with its associated exact confidence interval, based on the binomial distribution. The proportion of adverse event will also be given in the controlgroup. It must be stressed that no formal comparison (i.e. implying a statistical test), will be used to compare the two groups. Indeed, since the study is a phase I/II trial, it is not meant to provide a formal superiority or non- inferiority test and then is not powered for such a comparison |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Any important adverse events occurring from the time of signing of the informed consent, throughout the screening period and clinical trial, up to and including the last visit at M6.
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Adverse event reporting additional description |
AE and SAE are reported as : Treatment Emergent Adverse Event
For the SoC arm, a TEAE is any AE that occurred after randomization to the SoC arm.
For the ProtheraCytes® arm, a TEAE is any AE that occurred during or after the first administration of ProtheraCytes
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25
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Reporting groups
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Reporting group title |
PPSS Population
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Reporting group description |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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22 Mar 2017 |
Feasibility
Relaxing calendar constraints for the limit date for the screening phase
Concomitant treatments
Request, if possible, for ICD implantation location on the right side of the
body in order to limit CMR artifact
Inclusion criteria
Patient's upper limit age increased from 75 to 80 |
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05 Nov 2019 |
Trial management
Subcontracting vigilance, data management, statistics and monitoring
activities to CROs
Assessment
99mTc-SPECT became optional
Patient profile
The assessment of non-viable segments is performed by CMR instead of
SPECT
Data analysis
Addition of the two intermediate analyses at about 1/3 and 2/3 of the
recruitment |
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17 Sep 2020 |
Trial Management
Constitution of the study steering committee
Patient profile
AMI not limited to anterior location any more
Stenting not mandatory any more
Addition of Troponin peak >70x ULN inclusion criteria in order to limit the
rate of screen failures
FEVG threshold increased from 45% to 50%
Patient's upper limit age increased from 80 to 85
Feasibility
Relaxing calendar constraints up to two months post AMI for the limit date of
ProtheraCytes® injection
Switch from split G-CSF half doses of 5 μg/kg to a single dose of 10 μg/kg/day |
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02 Aug 2021 |
Safety
Urgent safety measure adding mandatory Echography for monitoring
pericardial effusion after the transendocardial injection procedure
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21 Oct 2021 |
Safety
Safety Leukocytosis threshold for G-CSF dose cancellation increased form
50G/L to 60 G/L
Inclusion criteria
Clarification of the definition of non-viable segment combining transmurality
>50% and akinesia/dyskinesia
Possibility to enroll non reperfused patients and patients who healed from
Hepatitis B
Initial investigational product specifications
CD34+ cell count change from "≥ 10x106" to "≥ 8x106"
Purity change from "≥ 85%" to "≥ 80%"
Monocytes changes from "≤ 10%" to "≤ 15%"
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12 Apr 2022 |
Study design
Change of the randomization ratio from 3:1 to 7:1 after the completion of the
Standard of Care arm
Assessment
Constitution of the CEC for the adjudication of MACE
Feasibility
Relaxing calendar constraint for randomization from 14 days to 28 days
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27 Mar 2023 |
Study procedure
Adding the possibility to treat via the intracoronary delivery pathway the
patients diagnosed pre-injection with LV thrombus without impacting the
power of the study, the required number of patients injected
transendocardially remaining the same. Patients intracoronarly injected will
not be analyzed per protocol.
Feasibility
Relaxing calendar constraints for the pre-injection CMR pathway to R15 (±2)
for facilitating the pre-injection detection of LV thrombus
Product specification update:
CD34+ Cell Count changes from "≥ 8x106" to "≥ 7.6x106"
Purity changes from "≥ 85%" to "≥ 76%"
Viability changes from ">95%" to "≥ 90%" |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/39676512 http://www.ncbi.nlm.nih.gov/pubmed/40929748 |
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