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

Rheumatoid Arthritis Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02092961
• Other study ID #: D4300C00004Sub
• Status: Terminated
• Phase: Phase 2
• First received: March 19, 2014
• Last updated: May 28, 2014
• Start date: February 2011
• Est. completion date: July 2013

Study information

• Verified date: April 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Public Health InstituteSlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 198
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Fostamatinib
Fostamatinib 100mg twice daily.
• Adalimumab
Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.
• Placebo of Fostamatinib
Placebo bid for 6 weeks.
• Placebo of Adalimumab
Placebo injection once every two weeks.

Locations

Country	Name	City	State
Bulgaria	Research Site	Pleven
Canada	Research Site	Mississauga	Ontario
Czech Republic	Research Site	Prague
Germany	Research Site	Hamburg
Germany	Research Site	Munich
Hungary	Research Site	Balatonfüred
Hungary	Research Site	Budapest
Netherlands	Research Site	Amsterdam
Poland	Research Site	Warsaw
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Durban
South Africa	Research Site	Pretoria
South Africa	Research Site	Stellenbosch
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Oxford
United States	Research Site	Austin	Texas
United States	Research Site	Brooklyn	New York
United States	Research Site	Glendale	Arizona
United States	Research Site	Jackson	Tennessee
United States	Research Site	Paradise Valley	Arizona
United States	Research Site	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czech Republic,  Germany,  Hungary,  Netherlands,  Poland,  Russian Federation,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	OMERACT RAMRIS Osteitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)	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.	Baseline, 6 and 24 weeks	No
Other	Joint Space Narrowing - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)	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.	Baseline, 6 and 24 weeks	No
Other	OMERACT RAMRIS Erosions Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)	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.	Baseline, 6 and 24 weeks	No
Other	DAS-CRP Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab	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.	Baseline, 6 and 24 weeks	No
Primary	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.	Baseline, 6 and 24 weeks	No