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

NCT ID: NCT02092961

Last Updated: 2014-06-25

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2013-07-31

Brief Summary

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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

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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.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dosing Group A

Oral treatment and subcutaneous injection.

Group Type EXPERIMENTAL

Fostamatinib

Intervention Type DRUG

Fostamatinib 100mg twice daily.

Placebo of Adalimumab

Intervention Type DRUG

Placebo injection once every two weeks.

Dosing Group D

Oral treatment and subcutaneous injection.

Group Type ACTIVE_COMPARATOR

Adalimumab

Intervention Type DRUG

Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.

Placebo of Fostamatinib

Intervention Type DRUG

Placebo bid for 6 weeks.

Dosing Group E

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

Group Type PLACEBO_COMPARATOR

Fostamatinib

Intervention Type DRUG

Fostamatinib 100mg twice daily.

Placebo of Fostamatinib

Intervention Type DRUG

Placebo bid for 6 weeks.

Placebo of Adalimumab

Intervention Type DRUG

Placebo injection once every two weeks.

Interventions

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Fostamatinib

Fostamatinib 100mg twice daily.

Intervention Type DRUG

Adalimumab

Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.

Intervention Type DRUG

Placebo of Fostamatinib

Placebo bid for 6 weeks.

Intervention Type DRUG

Placebo of Adalimumab

Placebo injection once every two weeks.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neil MacKillop, MD PhD

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Research Site

Glendale, Arizona, United States

Site Status

Research Site

Paradise Valley, Arizona, United States

Site Status

Research Site

Phoenix, Arizona, United States

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Brooklyn, New York, United States

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Jackson, Tennessee, United States

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Austin, Texas, United States

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Research Site

Pleven, , Bulgaria

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Mississauga, Ontario, Canada

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Prague, , Czechia

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Hamburg, , Germany

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Munich, , Germany

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Balatonfüred, , Hungary

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Budapest, , Hungary

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Amsterdam, , Netherlands

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Warsaw, , Poland

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Yaroslavl, , Russia

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Durban, , South Africa

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Pretoria, , South Africa

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Stellenbosch, , South Africa

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Manchester, , United Kingdom

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Research Site

Oxford, , United Kingdom

Site Status

Countries

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United States Bulgaria Canada Czechia Germany Hungary Netherlands Poland Russia South Africa United Kingdom

Other Identifiers

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D4300C00004Sub

Identifier Type: -

Identifier Source: org_study_id

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