Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study (OSKIRA 4 SS)

AstraZeneca

Status and phase: Terminated; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo of Adalimumab; Drug: Adalimumab; Drug: Placebo of Fostamatinib; Drug: Fostamatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02092961

D4300C00004Sub

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 198 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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198 participants in 3 patient groups, including a placebo group

Dosing Group A

Experimental group

Description:

Oral treatment and subcutaneous injection.

Treatment:

Drug: Fostamatinib

Drug: Placebo of Adalimumab

Dosing Group D

Active Comparator group

Description:

Oral treatment and subcutaneous injection.

Treatment:

Drug: Placebo of Fostamatinib

Drug: Adalimumab

Dosing Group E

Placebo Comparator group

Description:

Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.

Treatment:

Drug: Placebo of Fostamatinib

Drug: Fostamatinib

Drug: Placebo of Adalimumab