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A Trial of Cardiac Injections of iMP Cells During CABG Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03515291
Recruitment Status : Unknown
Verified January 2020 by Cell Therapy Ltd..
Recruitment status was:  Not yet recruiting
First Posted : May 3, 2018
Last Update Posted : January 27, 2020
Sponsor:
Collaborator:
Royal Brompton & Harefield NHS Foundation Trust
Information provided by (Responsible Party):
Cell Therapy Ltd.

Tracking Information
First Submitted Date  ICMJE April 20, 2018
First Posted Date  ICMJE May 3, 2018
Last Update Posted Date January 27, 2020
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
LGE-CMR [ Time Frame: Baseline and 15±2 weeks post surgery ]
Change in left ventricular LGE-CMR imaging (e.g. scar/fibrosis volume reduction), iMP group compared to control group.
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
LGE-MRI [ Time Frame: Baseline and 6 months post surgery ]
Change in left ventricular LGE-MRI imaging (e.g. scar/fibrosis reduction), iMP group compared to control group.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • LGE-CMR [ Time Frame: Baseline and 15±2 weeks post surgery ]
    Difference in Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-Diastolic Volume Index (LVEDVi), Left Ventricular End-Systolic Volume Index (LVESVi), LV late gadolinium enhancement pattern, myocardial perfusion and myocardial strain.
  • Major Adverse Cardiac Events (MACE) [ Time Frame: Recorded 1 month and 15±2 weeks post surgery ]
    Comparison of MACE rates between the two groups - Cardiovascular death, non fatal MI, non fatal stroke and unplanned cardiovascular hospitalisation.
  • Major arrhythmic events [ Time Frame: Recorded 1 month and 15±2 weeks post surgery ]
    Comparison of rates between the two groups.
  • All cause mortality [ Time Frame: Recorded 1 month and 15±2 weeks post surgery ]
    Comparison of rates between the two groups.
  • New York Heart Association (NYHA) Class [ Time Frame: Baseline and 15±2 weeks post surgery ]
    Assessment of difference in NYHA class between groups.
  • Quality of life questionnaires [ Time Frame: Baseline and 15±2 weeks post surgery ]
    Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure (MLHF) questionnaire and the EQ5D questionnaire - compared between the two groups.
  • Length of stay in intensive care/high dependency unit and time to discharge [ Time Frame: Operation date until discharge from hospital date, assessed up to 30 days post surgery. ]
    Comparison of length of stay in intensive care/high dependency unit and time to discharge - compared between the two groups.
  • Blood biomarkers (routine and exploratory) [ Time Frame: Baseline, 4 times during the post operative recovery period (12h, 24h, 48h and 72h) and at 1 week, 30 days and 15±2 weeks post surgery. ]
    Blood biomarkers related to cardiac function. Routine - Urea and electrolytes, liver function tests and full blood count. Exploratory - Uric acid, lipid profile, high sensitivity C reactive protein, high sensitivity troponin, N terminal pro brain natriuretic peptide. Levels compared between the two groups.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
  • LGE-MRI [ Time Frame: Baseline and 6 months post surgery ]
    Difference in Left Ventricular End-Diastolic Volume Index (LVEDVi), Left Ventricular End-Systolic Volume Index (LVESVi), Left Ventricular Ejection Fraction (LVEF), Late Gadolinium pattern, extent of fibrosis and strain analysis (wall motion and thickness) between groups.
  • Major Adverse Cardiac Events (MACE) [ Time Frame: Recorded 30 days, 3 months, 6 months and 12 months post surgery ]
    Comparison of MACE rates between the two groups.
  • New York Heart Association (NYHA) Class [ Time Frame: Baseline and 6 months post surgery ]
    Assessment of difference in NYHA class between groups
  • Quality of life questionnaires [ Time Frame: Baseline and 6 months post surgery ]
    Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure questionnaire - compared between the two groups.
  • Quality of life questionnaires [ Time Frame: Baseline and 12 months post surgery ]
    Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure questionnaire - compared between the two groups.
  • Length of stay in intensive care/high dependency unit and time to discharge [ Time Frame: Operation date until discharge from hospital date, assessed up to 30 days post surgery. ]
    Comparison of length of stay in intensive care/high dependency unit and time to discharge - compared between the two groups.
  • Blood biomarkers (routine and exploratory) [ Time Frame: Baseline, 4 times during the post operative recovery period (72 hours) and at 1 week, 30 days, 6 months and 12 months post surgery. ]
    Blood biomarkers related to cardiac function. Routine - Urea and electrolytes, liver function tests and full blood count. Exploratory - Uric acid, lipid profile, high sensitivity C reactive protein, high sensitivity troponin, N terminal pro brain natriuretic peptide. Levels compared between the two groups.
  • Blood test - Assessment of immunogenicity [ Time Frame: Baseline and 30 days post surgery. ]
    Humoral response assay to assess immunogenicity: Tests for immunoglobulins (Ig) - IgG1-4, IgM, IgA and IgE. Levels compared between the two groups.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Cardiac Injections of iMP Cells During CABG Surgery
Official Title  ICMJE A Phase IIB, Randomised, Double-Blinded, Placebo-Controlled Study of the Efficacy and Safety of Intramyocardial Injection of Allogeneic Human iMP Cells in Patients Undergoing CABG Surgery.
Brief Summary

Injury to the heart, which may occur following a heart attack or owing to the mechanical effect of high blood pressure, leads to scarring (fibrosis) of the heart muscle. Fibrosis of the muscle can cause impaired pumping of the heart, which can lead to heart failure, and the abnormal conduction of electrical signals through the heart. This may in turn lead to abnormal, potentially fatal, heart rhythms. Currently, scarring of the heart muscle cannot be reversed and is generally progressive.

A previous clinical study found that participants who received injections of immunomodulatory progenitor cells (iMP cells, "Heartcel") showed a reversal of heart muscle scarring when the cells were injected into heart muscle during coronary artery bypass graft (CABG) surgery. However, the previous trial was a small scale study and did not have a control group. The aim of this study is to perform a larger scale investigation with 50 participants compared to the previous trial of 11, and split the 50 participants into two groups - a test group and a control group, so that a direct comparison may be made between the two groups.

Detailed Description

Myocardial fibrosis is a currently untreatable medical condition. A previous trial reported that when iMP cells, a cell type of mesodermal lineage which is separate from, but shares characteristics with, mesenchymal stem cells (MSCs), were injected into the myocardium during CABG surgery, there was a reduction in the degree of scarring relative to baseline observed on 4 month and 12 month Single-Photon Emission Computed Tomography (SPECT) images.

The previous trial was open label with 11 participants and no control group, only historic comparisons. The proposed trial will be larger and will include a control group. The trial endpoints have been updated to take account of the findings of the first trial and late gadolinium enhanced (LGE) Magnetic Resonance Imaging (MRI) scans (LGE-CMR), which have higher resolution than SPECT scans, will be used to assess the appearance of fibrosis.

iMP cells were developed by the sponsor as an allogeneic mesodermally derived cellular therapy for cardiac conditions. While iMPs are plastic adherent like MSCs, iMPs do not meet the International Society for Cellular Therapy's definition of MSCs, though like MSCs, markers indicate that iMPs are immune privileged and can therefore be employed allogeneically without inducing a significant immune response.

The trial is open to participants, male and female, who require CABG surgery and have 15% or greater left ventricular scarring. Unless part of normal clinical care, participants will be required to undergo a screening LGE-MRI to assess the degree of left ventricular scarring. The MRI however, may reveal that the individual is not eligible to participate in the study. If the individual is eligible, then the LGE-MRI will be used as the baseline recording and to plan the injection sites.

Each participant will be involved in the study for approximately 4.5 months. There will be two outpatient pre-operative hospital visits which will occur up to 6 weeks prior to surgery, though if a potential participant is an inpatient, the pre-operative eligibility/baseline tests can be performed over a shorter period of time as an inpatient. The CABG surgery will not differ from normal, except for the injections into the heart muscle, and participants will not miss out on any standard care. There will then be follow up visits at 1 week, 1 month and 15±2 weeks post surgery. The 1 week visit may occur as an inpatient depending on post-operative improvement. The follow up visits will not involve overnight stays. Follow up visits will mainly entail an ECG, an echocardiogram, a blood test, a urine test, health questionnaires and a discussion about the participant's health and any adverse events. Specific details are available from the chief investigator, see below. The 15±2 week visit will also involve a follow up LGE-MRI for primary endpoint assessment. After this visit, participation in the study will end and participants will receive only the normal post CABG care.

As this is a quadruple blind randomised controlled trial, neither participants nor care staff will know to which group a participant is allocated. Of the 50 participants, 30 will receive injections of cells and 20 will receive control injections.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Myocardial Fibrosis
Intervention  ICMJE
  • Biological: iMP cells
    Immunomodulatory progenitor cells
    Other Name: "Heartcel"
  • Other: Control injection
    Cell suspension solution
Study Arms  ICMJE
  • Experimental: iMP cell injection
    iMP cells injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.
    Intervention: Biological: iMP cells
  • Placebo Comparator: Control injection
    Control (cell suspension solution) injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.
    Intervention: Other: Control injection
Publications * Anastasiadis K, Antonitsis P, Westaby S, Reginald A, Sultan S, Doumas A, Efthimiadis G, Evans MJ. Implantation of a Novel Allogeneic Mesenchymal Precursor Cell Type in Patients with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting: an Open Label Phase IIa Trial. J Cardiovasc Transl Res. 2016 Jun;9(3):202-213. doi: 10.1007/s12265-016-9686-0. Epub 2016 Apr 1. Erratum in: J Cardiovasc Transl Res. 2021 Jun;14(3):587-588.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 2, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Greater than or equal to 15% LV scar volume measured by LGE-CMR.

LVEF ≤50%.

Ischaemic heart disease where CABG is the recommended revascularisation strategy.

Age range: 18 years of age and over with no history of congenital cardiac anomalies (men and women).

Able to provide written informed consent (including willingness to have two CMRs).

New York Heart Association (NYHA) class >=2 and/or Canadian Cardiovascular Society (CCS) class angina >=2.

For women of child bearing potential (WOCBP): Negative (non-pregnant) beta-human chorionic gonadotropin (beta-hCG) blood test.

Exclusion Criteria:

Previous cardiac surgery

Requirement for additional cardiac surgery including concomitant valve replacement surgery.

Estimated GFR of <30mL/min

Contraindication to performance of CMR

Clinical history of malignancy within 5 years

Comorbidities likely to influence the safety of performing the protocol

Liver disease including ALT 3 times or more the upper limit of normal

Low platelet count (<100,000) platelets per microliter of blood

Evidence of coagulopathy - International Normalised Ratio (INR) >2. Note: Elevated INR due solely to warfarin (or similar medication) is NOT an exclusion criterion.

Increased mortality risk over a 12-month period due to comorbidity

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Female participants must not be pregnant (negative beta hCG test).
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03515291
Other Study ID Numbers  ICMJE CLX003-IMP-2-170121
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Cell Therapy Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cell Therapy Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Royal Brompton & Harefield NHS Foundation Trust
Investigators  ICMJE
Study Director: Nigel Scott, MB BChir PhD Cell Therapy Ltd.
PRS Account Cell Therapy Ltd.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP