Clinical trial NCT02092961: Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
OSKIRA
fostamatinib
CE-MRI
DCE-MRI
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-03-20
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
timeFrame: Baseline, 6 and 24 weeks
Secondary outcomes:
Other outcomes:
measure: OMERACT RAMRIS Osteitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
timeFrame: Baseline, 6 and 24 weeks
measure: Joint Space Narrowing - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
timeFrame: Baseline, 6 and 24 weeks
measure: OMERACT RAMRIS Erosions Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
timeFrame: Baseline, 6 and 24 weeks
measure: DAS-CRP Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab
timeFrame: Baseline, 6 and 24 weeks
Locations:
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Paradise Valley
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Jackson
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Pleven
country: Bulgaria
facility: Research Site
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Prague
country: Czech Republic
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Munich
country: Germany
facility: Research Site
city: Balatonfüred
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Stellenbosch
country: South Africa
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Neil MacKillop, MD PhD
role: STUDY_DIRECTOR
References: