A Trial of Cardiac Injections of iMP Cells During CABG Surgery
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.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: iMP cell injection
iMP cells injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.
|
Immunomodulatory progenitor cells
Other Names:
|
|
Placebo Comparator: Control injection
Control (cell suspension solution) injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.
|
Cell suspension solution
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Baseline and 15±2 weeks post surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
Baseline and 15±2 weeks post surgery
|
|
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.
|
Recorded 1 month and 15±2 weeks post surgery
|
|
Major arrhythmic events
Time Frame: Recorded 1 month and 15±2 weeks post surgery
|
Comparison of rates between the two groups.
|
Recorded 1 month and 15±2 weeks post surgery
|
|
All cause mortality
Time Frame: Recorded 1 month and 15±2 weeks post surgery
|
Comparison of rates between the two groups.
|
Recorded 1 month and 15±2 weeks post surgery
|
|
New York Heart Association (NYHA) Class
Time Frame: Baseline and 15±2 weeks post surgery
|
Assessment of difference in NYHA class between groups.
|
Baseline and 15±2 weeks post surgery
|
|
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.
|
Baseline and 15±2 weeks post surgery
|
|
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.
|
Operation date until discharge from hospital date, assessed up to 30 days post surgery.
|
|
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.
|
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.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Nigel Scott, MB BChir PhD, Cell Therapy Ltd.
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLX003-IMP-2-170121
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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