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

Primary Purpose

Rheumatoid Arthritis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fostamatinib
Adalimumab
Placebo of Fostamatinib
Placebo of Adalimumab
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, OSKIRA, fostamatinib, CE-MRI, DCE-MRI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Dosing Group A

Dosing Group D

Dosing Group E

Arm Description

Oral treatment and subcutaneous injection.

Oral treatment and subcutaneous injection.

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

Outcomes

Primary Outcome Measures

OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
OMERACT RAMRIS synovitis score was based on 8 joints, scored from MRI images, and ranged from 0 to 24 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.

Secondary Outcome Measures

Full Information

First Posted
March 19, 2014
Last Updated
May 28, 2014
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02092961
Brief Title
Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study
Acronym
OSKIRA 4 SS
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

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
AZ decision to discontinue fostamatinib development in RA; rights to fostamatinib returned to Rigel Pharmaceuticals.
Study Start Date
February 2011 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, OSKIRA, fostamatinib, CE-MRI, DCE-MRI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
198 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dosing Group A
Arm Type
Experimental
Arm Description
Oral treatment and subcutaneous injection.
Arm Title
Dosing Group D
Arm Type
Active Comparator
Arm Description
Oral treatment and subcutaneous injection.
Arm Title
Dosing Group E
Arm Type
Placebo Comparator
Arm Description
Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib 100mg twice daily.
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Intervention Description
Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo of Fostamatinib
Intervention Description
Placebo bid for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo of Adalimumab
Intervention Description
Placebo injection once every two weeks.
Primary Outcome Measure Information:
Title
OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
Description
OMERACT RAMRIS synovitis score was based on 8 joints, scored from MRI images, and ranged from 0 to 24 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.
Time Frame
Baseline, 6 and 24 weeks
Other Pre-specified Outcome Measures:
Title
OMERACT RAMRIS Osteitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
Description
OMERACT RAMRIS osteitis score was based on 25 joints, scored from MRI images, and ranged from 0 to 75 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.
Time Frame
Baseline, 6 and 24 weeks
Title
Joint Space Narrowing - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
Description
Joint space narrowing score was based on 20 joints, scored from MRI images and ranged from 0 to 80 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, JSN = joint space narrowing, MRI = magnetic resonance imaging, PO = orally, SC = subcutaneous.
Time Frame
Baseline, 6 and 24 weeks
Title
OMERACT RAMRIS Erosions Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)
Description
OMERACT RAMRIS erosions score was based on 25 joints and ranged from 0 to 250 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.
Time Frame
Baseline, 6 and 24 weeks
Title
DAS-CRP Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab
Description
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, PO = orally, SC = subcutaneous.
Time Frame
Baseline, 6 and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil MacKillop, MD PhD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Glendale
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Paradise Valley
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
Research Site
City
Jackson
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Austin
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Pleven
Country
Bulgaria
Facility Name
Research Site
City
Mississauga
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Munich
Country
Germany
Facility Name
Research Site
City
Balatonfüred
Country
Hungary
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Amsterdam
Country
Netherlands
Facility Name
Research Site
City
Warsaw
Country
Poland
Facility Name
Research Site
City
Yaroslavl
Country
Russian Federation
Facility Name
Research Site
City
Durban
Country
South Africa
Facility Name
Research Site
City
Pretoria
Country
South Africa
Facility Name
Research Site
City
Stellenbosch
Country
South Africa
Facility Name
Research Site
City
Manchester
Country
United Kingdom
Facility Name
Research Site
City
Oxford
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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