A Trial of Cardiac Injections of iMP Cells During CABG Surgery

NCT ID: NCT03515291

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-31
• Study Completion Date: 2021-07-31

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.

Conditions

Myocardial Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

iMP cell injection

iMP cells injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.

Group Type: EXPERIMENTAL

iMP cells

Intervention Type: BIOLOGICAL

Immunomodulatory progenitor cells

Control injection

Control (cell suspension solution) injected in to the epicardial surface of the heart during coronary artery bypass graft surgery.

Group Type: PLACEBO_COMPARATOR

Control injection

Intervention Type: OTHER

Cell suspension solution

Interventions

iMP cells

Immunomodulatory progenitor cells

Intervention Type: BIOLOGICAL

Control injection

Cell suspension solution

Intervention Type: OTHER

Other Intervention Names

"Heartcel"

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Cell Therapy Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nigel Scott, MB BChir PhD

Role: STUDY_DIRECTOR

Cell Therapy Ltd.

Central Contacts

Ali Vazir, MBBS, PhD

Role: CONTACT

a.vazir@imperial.ac.uk

+44 (0)20 7352 8121

References

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.

Reference Type: BACKGROUND

PMID: 27037806 (View on PubMed)

Other Identifiers

CLX003-IMP-2-170121

Identifier Type: -

Identifier Source: org_study_id