Evaluation of Efficacy and Safety of Fostamatinib Monotherapy Compared With Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (RA)

Sub-study:

Full title: Optional Genetic Research

Date: 10 September 2010

Version: 1

Objectives: To collect and store, with appropriate consent , DNA samples for future
exploratory research into genes/genetic variation that may influence response (ie,
absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to
fostamatinib disodium and/or adalimumab; and/or susceptibility to, progression of and
prognosis of RA

The main study recruitment is complete, and sub study recruitment will continue until the
target is reached, estimated to be June 2013

Sub-study:

Full title: (Sub-study to OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind,
Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium
Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active
Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study

Date: 21 March 2011

Version: 1

Primary objective: Assess the efficacy of fostamatinib in reducing joint synovial disease
activity as measured by:

- Change from baseline to Week 6 (versus placebo) in OMERACT RAMRIS synovitis score.

Inclusion Criteria:

- Male or female aged 18 and over

- Active rheumatoid arthritis (RA) diagnosed after the age of 16 and 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)
and 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)

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