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  • Periodic Report Summary 3 - BAMI (The effect of intracoronary reinfusion of bone marrow-derived mononuclear cells (BM-MNC) on all-cause mortality in acute myocardial infarction)

BAMI Report Summary

Project ID: 278967
Funded under: FP7-HEALTH
Country: United Kingdom

Periodic Report Summary 3 - BAMI (The effect of intracoronary reinfusion of bone marrow-derived mononuclear cells (BM-MNC) on all-cause mortality in acute myocardial infarction)

Project Context and Objectives:
Previous research studies conducted over the past decade have shown overall that autologous bone marrow derived mononuclear cells (BM-MNC) administration post acute myocardial infarction (AMI) is safe and can be associated with beneficial clinical outcomes. Enough data exists to warrant the conduct of a pre-licensing trial to establish whether BM-MNC therapy post AMI will benefit patients in addition to standard care.

The current study is a Phase III multinational, multi centre, randomised, open label, controlled, parallel-group outcome study which aims to demonstrate that a single intracoronary infusion of autologous BM-MNC in addition to optimal reperfusion therapy, reduces all-cause mortality compared to optimal reperfusion therapy alone. Additionally, the study is looking at Major Adverse Cardiac Events as secondary efficacy endpoints. The study has developed a standardised, evidence based method for cell preparation that could be delivered in hospitals across the EU should the trial yield positive results. According to current information there are no other competing Phase III trials planned.

Project Results:
Setting up of the study
Existing data regarding bone marrow aspirations techniques and cell harvest were reviewed. Different procedures for bone marrow processing to deliver the desired mononuclear cell fraction were compared: (i) a central processing facility approach based on t2cure’s Advanced Therapeutic Medicinal Product t2c001, (ii) a medical-devices driven point-of-care (POC) bedside approach. The consortium decided that the t2cure method would be most likely to yield a positive result in the clinical trial, based on preclinical/clinical data. Standard Operating Procedures (SOPs) for bone marrow preparation and cell optimisation, and efficacy and quality release criterion for the final product were created.

The consortium selected the best method of cell delivery. Several different techniques are available for delivery of cell therapy. In the context of AMI, intracoronary infusion is the most common route of delivery and has the largest evidence base in relation to methodology and safety issues. The technique employs balloon angioplasty and cell infusion through an over-the-wire (OTW) balloon. This is the injection technique used in conjunction with t2c001 in previous clinical trials and has been chosen for use in BAMI. An SOP on the cell infusion technique and a technical report of injection catheter characteristics were produced.

The trial protocol and statistical analysis plan were devised. The study is performed with a group sequential design, with one final analysis. The Data Monitoring Committee (DMC) will perform regular reviews. The Clinical Events Committee (CEC), undertakes adjudication of end-points and events. These 2 committees that have been set up are part of the required governance structure to conduct clinical trials such as BAMI.

The Sponsor put numerous contracts in place between the various parties, delegating responsibilities appropriately to ensure smooth running of the study.

The Sponsor ensured that the relevant approvals were obtained prior to trial initiation. The BAMI trial has been the first study of its size to have successfully undergone the Voluntary Harmonisation Procedure followed by Local Competent Authorities (LCAs) and Ethics Committees approval in each Member State.

A total of 8 partners have been initiated and are actively recruiting:
P1 – QMUL (UK)
P3 – GUH (BE)
P9 – VZW (BE)
P11 – FN Brno (CZ)
P12 - RegionH (DK)
P13 - UCSC (IT)
P18 – UEF (FI)
P22 – UHF (DE)

Additionally there are 34 active satellite sites across Europe and 229 patients have been recruited so far. Two partners have left the consortium since the beginning of the project P16 UR and P 19 OUS. P15 SUM has reviewed the feasibility of the study based on the various issues they have faced in setting the trial up together with the recent additional financial burden, and have decided that patient recruitment will not be feasible at their site.

Originally the trial had 7 Cell Processing Centres (CPCs) identified across Europe. However the Voluntary Harmonisation Procedure (VHP) brought to light that only 3 CPC’s were Good Manufacturing Practice (GMP) compliant and therefore these have been the only ones approved to process the cells on the BAMI trial. Two new GMP compliant CPC’s (1 in the UK and 1 in Switzerland) have been worked up to start processing for the BAMI trial. Once these 2 CPCs are fully functional we will have a total of 5 CPCs. With the existing CPCs it has been possible for all countries to send and receive cells within required timeframes. The additional cell processing centres will reduce current logistical issues and allow new sites to be opened.

Since the previous report, the project has undergone 1 substantial amendment which has been approved by the VHP, and Local Ethics Committees and LCAs in each Member State.

As planned, the Independent DMC and CEC have been set up and have met to review trial safety and endpoints. Up to now there have been no safety issues.

Potential Impact:
The impact of the study remains the same as in the previous report. It is expected that the BAMI trial will demonstrate a positive effect on mortality in patients undergoing primary angioplasty. We estimate that cell therapy may be used in 30% of these procedures, which implies that for 300,000 patients suffering a heart attack we might:
A. reduce the mortality rate by 25% and hence save 6000 lives and
B. reduce the rehospitalisation rate by 15% with an associated decrease in hospital costs.

The economic losses related to patients with acute myocardial infarction are summarized as follows:
1. IMMEDIATE SICK LEAVE ASSOCIATED WITH THE AMI EVENT AND TREATMENT FOLLOW UP – we estimate that typical sufferers take 4 weeks off work as a result of a rehospitalisation event. In Europe, the estimated impact is:
• Reduction in days lost associated with the AMI treatment and care of 500,000 days/annum
• Associated employment cost saving of €3755 million p.a. (based on average of €750/day cost to European employers)

2. LONG TERM SICKNESS AND INCAPACITY TO WORK ASSOCIATED WITH A CHRONIC HEART CONDITION – we estimated that 10,000 European citizens per year have their careers cut short by a heart condition. In Europe, the estimated impact is
• Assuming a decade of lost employment per AMI sufferer, income loss would be €450,000 on average
• The AMI sufferer’s income loss burden would be diverted onto European social welfare systems, averting these 10,000 sufferers per year could save European social systems €70 to 100 million

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Reported by

United Kingdom


Life Sciences
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