MORE2 v1.0
Research type
Research Study
Full title
MACROPHAGE FOR REGENERATIVE MEDICINE IN CIRRHOTICS – II
IRAS ID
229265
Contact name
Stuart Forbes
Contact email
Sponsor organisation
University of Edinburgh
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
1 years, 4 months, 27 days
Research summary
Research Summary
Cirrhosis of the liver is the end process of continuous injury to the organ by any cause. There is currently no treatment beside liver transplant for cirrhosis. Prof Forbes group has worked for years on the development of cellular therapy to cure cirrhosis.
This study is looking to improve a currently used method to produce cellular therapy for patients with cirrhosis of the liver. We are running a parallel study (MATCH) to compare this cellular therapy in cirrhotic patients against standard of care. The Blood Transfusion team and the scientists at the University of Edinburgh are looking to make the production process more streamlined allowing larger scale production and reducing production time. This will be a step towards widespread production of a potentially curative therapy for cirrhosis of the liver and also will allow the opening of the MATCH trial multicentre across UK.Summary of Results
The MATCH clinical trial investigated the therapeutic potential of autologous activated macrophages as a novel cell therapy for patients with cirrhosis. The treatment involved the collection of peripheral monocytes form participants via apheresis, followed by ex vivo differentiation into macrophages under good manufacturing practice (GMP) conditions. The long-term objective of the MORE2 study was to expand the manufacturing capability beyond a single centre, enabling wider patient access to this innovative treatment across the UK and to support future clinical studies.This feasibility study (MORE2) was undertaken as an important step towards achieving that objective. The study aimed to optimise and simplify the GMP manufacturing process for monocyte-derived autologous activated macrophages to facilitate production at multi-manufacturing sites. Specifically, the study evaluated the feasibility of prolonged transport and overnight storage of the apheresis products prior to GMP processing and measured extended stability of the final macrophage product. It was also used to transfer manufacturing to a second manufacturing facility, increasing manufacturing capacity.
Two of the collections were used to manufacture macrophage products using the MATCH manufacturing protocols with the following changes:
- Overnight storage of starting material (leukapheresis product) prior to manufacture
- Transport to a second manufacturing facility for manufacture
- Manufacture at a second manufacturing facility
- Transport of QC (quality control) samples between different sites to facility testing
The data from these runs were used to support the implementation of additional transport and storage time of starting material, enabling expansion of patient recruitment for the MATCH clinical trial to other areas of the UK. It was also used to demonstrate suitability of a second manufacturing facility and its equipment for manufacture of the MATCH product, increasing manufacturing capacity and flexibility.Five MORE2 donations were used to assess stability of final macrophage product when held at different cell density’s (concentration) and temperatures for storage up to 48hrs. The MATCH product is not cryopreserved so this data was required to support clinical product shelf life prior to infusion across all doses used in the MATCH clinical trial.
Successful implementation supported manufacture from centres across the UK, increased manufacturing flexibility and improved operational efficiency. The ultimate objective was met - to demonstrate the feasibility of multi-centre manufacturing and future expansion of the therapy’s availability across the UK.
REC name
West of Scotland REC 5
REC reference
19/WS/0006
Date of REC Opinion
18 Jan 2019
REC opinion
Favourable Opinion