Myocardial FibrosisPhase 2NCT03515291
A Trial of Cardiac Injections of iMP Cells During CABG Surgery
A Phase 2 study testing iMP cells in people with Myocardial Fibrosis, run by Cell Therapy Ltd..
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Fibrosis
- What is being tested?
- iMP cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Jan 2020to Jul 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read the 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
- Being tested
- iMP cells, Control injection
- Keywords
- Heart, CABG, Injection, Scar, Fibrosis, Cell, Progenitor, Immunomodulatory, MRI, Randomized
- Medical subject headings
- Cicatrix, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iMP cellsBiological
Also called "Heartcel"
Immunomodulatory progenitor cells
Control injectionOther
Cell suspension solution
| Study group | Role | What they receive |
|---|---|---|
| iMP cell injection | Experimental | iMP cells injected in to the epicardial surface of the heart during coronary artery bypass graft surgery. Receives: Biological: iMP cells |
| Control injection | Placebo comparator | Control (cell suspension solution) injected in to the epicardial surface of the heart during coronary artery bypass graft surgery. Receives: Other: Control injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
LGE-CMR
Change in left ventricular LGE-CMR imaging (e.g. scar/fibrosis volume reduction), iMP group compared to control group.
Measured: Baseline and 15±2 weeks post surgery
Secondary outcomes (8)
LGE-CMR
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.
Measured: Baseline and 15±2 weeks post surgery
Major Adverse Cardiac Events (MACE)
Comparison of MACE rates between the two groups - Cardiovascular death, non fatal MI, non fatal stroke and unplanned cardiovascular hospitalisation.
Measured: Recorded 1 month and 15±2 weeks post surgery
Major arrhythmic events
Comparison of rates between the two groups.
Measured: Recorded 1 month and 15±2 weeks post surgery
All cause mortality
Comparison of rates between the two groups.
Measured: Recorded 1 month and 15±2 weeks post surgery
New York Heart Association (NYHA) Class
Assessment of difference in NYHA class between groups.
Measured: Baseline and 15±2 weeks post surgery
Quality of life questionnaires
Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure (MLHF) questionnaire and the EQ5D questionnaire - compared between the two groups.
Measured: Baseline and 15±2 weeks post surgery
Length of stay in intensive care/high dependency unit and time to discharge
Comparison of length of stay in intensive care/high dependency unit and time to discharge - compared between the two groups.
Measured: Operation date until discharge from hospital date, assessed up to 30 days post surgery.
Blood biomarkers (routine and exploratory)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2018
- Study startJan 2020 (estimated)
- Primary completionJan 2021 (estimated)
- Study completionJul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cell Therapy Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Nigel Scott, MB BChir PhD, Study director, Cell Therapy Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03515291
- Sponsor's protocol ID
- CLX003-IMP-2-170121
- Status last verified
- Jan 2020
- First submitted
- 20 Apr 2018
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 27037806
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03515291
- Acronym / sponsor ID
- CLX003-IMP-2-170121
- Conditions
- Myocardial Fibrosis
- Keywords
- Heart, CABG, Injection, Scar, Fibrosis, Cell, Progenitor, Immunomodulatory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Cell Therapy Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Royal Brompton & Harefield NHS Foundation Trust
- Study start
- Jan 2020 (estimated)
- Primary completion
- Jan 2021 (estimated)
- Study completion
- Jul 2021 (estimated)
- First posted
- 3 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| iMP cell injection | Experimental | Biological: iMP cellsiMP cells injected in to the epicardial surface of the heart during coronary artery bypass graft surgery. |
| Control injection | Placebo comparator | Other: Control injectionControl (cell suspension solution) injected in to the epicardial surface of the heart during coronary artery bypass graft surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iMP cellsAlso: "Heartcel"Immunomodulatory progenitor cells | Biological | iMP cell injection |
| Control injectionCell suspension solution | Other | Control injection |
Primary outcome
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.
8 secondary outcomes
LGE-CMR
Time frame: Baseline and 15±2 weeks post surgery
Major Adverse Cardiac Events (MACE)
Time frame: Recorded 1 month and 15±2 weeks post surgery
Major arrhythmic events
Time frame: Recorded 1 month and 15±2 weeks post surgery
All cause mortality
Time frame: Recorded 1 month and 15±2 weeks post surgery
New York Heart Association (NYHA) Class
Time frame: Baseline and 15±2 weeks post surgery
Quality of life questionnaires
Time frame: 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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Background: PubMed 27037806Anastasiadis 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nigel Scott, MB BChir PhD study director
Cell Therapy Ltd.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing iMP cells in people with Myocardial Fibrosis, run by Cell Therapy Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ali Vazir, MBBS, PhD (+44 (0)20 7352 8121, a.vazir@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LGE-CMR (time frame: Baseline and 15±2 weeks post surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03515291, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.