Current Clinical Studies and Trials – Experimental Medicine & Rheumatology
PEAC Study - Pathobiology of Early Arthritis Cohort
[NIHR CRN Portfolio Study ID: 5339]
The MRC funded Pathobiology of Early Arthritis Cohort (PEAC) is being established through the contribution of a consortium of 5 independent, national centres of excellence. The specific aims of this project are to create an extensively phenotyped cohort of patients with early inflammatory arthritis with linked, detailed pathobiological data.
The development of a prospective early arthritis cohort with high quality clinical and imaging data (state-of-the-art 3D/4D ultrasound-US / power-Doppler-PDU imaging) together with a comprehensive collection of biological samples (blood, urine and synovial tissue) provides a unique resource to search for early predictors of disease evolution as well as to enable early proof of concept/mechanistic studies with stratified entry according to the imaging and immunological profile. Thus, this cohort represents an ideal platform for clinical trials of novel substances (see below).
R4-RA Clinical Trial - Trial A randomised, open labelled study in anti-TNFa inadequate responders to investigate the mechanisms for Response - Resistance to Rituximab versus Tocilizumab in RA
[NIHR CRN Portfolio Study ID: 14524]
Evidence from the Pathobiology of Early Arthritis Cohort initiative, in which synovial biopsies have been taken from patients with early arthritis, indicate that there are at least three distinct histo-morphological subtypes. These are described as fibroblast (pauci-immune), lymphoid (B-cell rich, with or without germinal centre formation) and Myeloid (rich in monocytes but poor in B cells), which correspond to different transcriptomic signatures.
With these subsets in mind, the overarching hypothesis of this study is whether a diagnostic synovial biopsy showing a “B-cell rich / B- cell poor” pathotype can predict response and define certain disease responsive / resistance subsets for patients stratification and help to rationalize drug choice. The purpose of this study is to test the hypothesis that the presence or absence of specific synovial and molecular signatures (B-cells and B-cell associated signatures), assessed through obtaining tissue from a synovial biopsy, will enrich for response / non-response to Rituximab, and B-cell depleting anti-CD20 monoclonal antibody. Patients are eligible if they have failed anti-TNF therapy and will undergo a synovial biopsy baseline and then be randomised to receive Rituximab or Tocilizumab.
This is a multi-site, multi-country clinical trial which aims to recruit 180 patients and is being led by the Centre for Experimental Medicine and Rheumatology. There will be approximately 10 additional centres participating in the trial both in the UK and Europe. The study commenced in February 2013 and we plan to recruit 180 patients over a 24 month period.
This study is being funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program (NIHR EME).
MATURA (STRAP) Clinical Trial - Maximising Therapeutic Utility in Rheumatoid Arthritis
Developing a novel, biopsy-based diagnostic for patient stratification for first biologic treatment: A Randomised, open-labelled study in DMARD inadequate responders:
Stratification of Therapy for RA by Pathobiology - STRAP Trial
Maximising Therapeutic Utility in Rheumatoid Arthritis (MATURA) is an ambitious research project jointly funded by MRC and Arthritis Research UK to identify and test biomarkers predictive of response to therapy in rheumatoid arthritis (RA), thereby allowing the stratification of patients into groups according to the therapies that are most likely to be effective. The project comprises two work-streams: Workstream 1 is managed by Prof Costantino Pitzalis the Centre for Experimental Medicine and Rheumatology, and Workstream 2 is managed at The University of Manchester.
An important component of the Workstream 1 is the STRAP Trial, a randomised control trial which aims to test the utility of synovial histomorphology and B cell number together with specific molecular signatures as potential biomarkers to guide therapeutic decisions in patients failing DMARD therapy to improve on current response rates and identify patients more likely to respond. Patients will be randomised to receive either Rituximab, Tocilizumab or Anti-TNF therapy following a baseline synovial biopsy.
This trial is still in the set-up phase but will be a multi-site, multi-country clinical trial aiming to recruit 180-220 patients over a period of 24 months.