Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Fostamatinib; Adalimumab; Placebo of Fostamatinib; Placebo of Adalimumab
Intervention description: Fostamatinib 100mg twice daily.; Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.; Placebo bid for 6 weeks.; Placebo injection once every two weeks.
Intervention MeSH terms: Adalimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; OSKIRA; fostamatinib; CE-MRI; DCE-MRI

Summary:

      This is a sub-study of the OSKIRA-4 study, (D4300C0004, NCT01264770) to explore alternative
      and more sensitive modalities for measuring the beneficial effects of syk inhibition with
      fostamatinib in patients with active RA. This MRI sub-study was reported later than the main
      study due to recruitment delays at specialist imaging sites and so is registered and
      presented entirely separately to the main study results.

      This study will investigate the impact of treatment on joint activity and damage by assessing
      synovitis, osteitis, bone erosions and joint space narrowing.
    

Eligibility criteria:

        Inclusion Criteria: -

          -  Male or female aged 18 and over

          -  Active rheumatoid arthritis (RA) diagnosed after the age of 16

          -  Diagnosis within 5 years prior to study visit 1 and inadequate response to treatment
             with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or

          -  diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or

          -  diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs

          -  4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count)

          -  Either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or

          -  C-Reactive Protein (CRP) blood result of 10mg/L or more

          -  At least 2 of the following:

               -  documented history or current presence of positive rheumatoid factor (blood
                  test),

               -  radiographic erosion within 12 months prior to study enrolment,

               -  presence of serum anti-cyclic citrullinated peptide antibodies (blood test)

               -  Presence of at least one swollen hand or wrist joint.

               -  Presence of synovitis on baseline MRI scan, defined as at least 1 joint with
                  RAMRIS synovitis score of +1 or greater.

        Exclusion Criteria:

          -  Females who are pregnant or breast feeding

          -  Poorly controlled hypertension

          -  Liver disease or significant liver function test abnormalities

          -  Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue
             diseases or chronic pain disorders

          -  Recent or significant cardiovascular disease

          -  Significant active or recent infection including tuberculosis

          -  Previously received treatment with a TNF alpha antagonist (including etanercept,
             certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment
             with other biological agent including rituximab, abatacept and tocilizumab

          -  Use of any DMARDs within 6 weeks before first study visit

          -  Severe renal impairment

          -  Neutropenia

          -  Unable to undergo an MRI examination (e.g. presence of a pacemaker, defibrillator, or
             other implanted metallic device such as anterior interbody cages, aneurysm clip or
             pedicle screws)

          -  Known allergy to Gadolinium-based contrast agent,

          -  Tattoos [in area of examination if contains metallic pigment]

          -  Likely to require sedation for the procedure

          -  eGFR less than 55 mL/min