Clinical trial NCT01197755: Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate and Have Had Inadequate Response to Single TNF-alpha Antagonist
Official title: (OSKIRA-3): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With Inadequate Response to a TNF-alpha Antagonist
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 323
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: The purpose of the study is to evaluate the effectiveness of two dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking methotrexate and have had an inadequate response to a single TNF-alpha antagonist. The study will last for approximately six months.

Detailed description: Sub-study:

Full title: Optional Genetic Research

Date: 18 June 2010

Version: 1

Objectives: To collect and store, with appropriate consent ,DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or methotrexate; and/or susceptibility to, progression of and prognosis of RA

Eligibility criteria: Inclusion Criteria:

* Active rheumatoid arthritis (RA) diagnosed after the age of 16
* Currently taking methotrexate
* 6 or more swollen joints and 6 or more tender/painful joints (from 28 joint count) and 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 one of the following: documented history of positive rheumatoid factor (blood test), current presence of rheumatoid factor (blood test), radiographic erosion within 12months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test)

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
* Previous failure to respond to anakinra or previous treatment with biological agent (other than TNF alpha antagonists including rituximab, abatacept and tocilizumab)
* Severe renal impairment
* Neutropenia

Primary outcomes:
measure: Proportion of Patients Achieving ACR20 at Week 24, Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo
timeFrame: 1 week
measure: Proportion of Patients Achieving ACR50 at Week 24, Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
measure: Proportion of Patients Achieving ACR70 at Week 24, Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
measure: ACRn - Comparison Between Fostamatinib and Placebo at Week 24
timeFrame: Baseline and 24 weeks
measure: Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
measure: Proportion of Patients Achieving DAS28-CRP <=3.2 at Week 12, Comparison Between Fostamatinib and Placebo
timeFrame: 12 weeks
measure: Proportion of Patients Achieving DAS28-CRP EULAR Response at Week 24, Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
measure: Proportion of Patients With a HAQ-DI Response at Week 24 - Comparison Between Fostamatinib and Placebo
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in mTSS Score, Comparison Between Fostamatinib and Placebo
timeFrame: Baseline and 24 weeks
measure: SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24
timeFrame: Baseline and 24 weeks
measure: SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Tuscaloosa
country: United States
facility: Research Site
state: Alabama
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Hot Springs
country: United States
facility: Research Site
state: Arkansas
city: Glendale
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Santa Maria
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Tustin
country: United States
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state: California
city: Upland
country: United States
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state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Bridgeport
country: United States
facility: Research Site
state: Connecticut
city: Trumbull
country: United States
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state: Connecticut
city: Lewes
country: United States
facility: Research Site
state: Delaware
city: Brandon
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Ocala
country: United States
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state: Florida
city: Orlando
country: United States
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state: Florida
city: Tampa
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state: Florida
city: Venice
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city: Zephyr Hills
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Canton
country: United States
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state: Georgia
city: Idaho Falls
country: United States
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state: Idaho
city: Decatur
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state: Illinois
city: Cedar Rapids
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state: Iowa
city: Bowling Green
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state: Kentucky
city: Elizabethtown
country: United States
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city: Crofton
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state: Maryland
city: Fall River
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state: Massachusetts
city: Worcester
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city: Lansing
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state: Michigan
city: Flowood
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city: Florissant
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state: Missouri
city: Richmond Heights
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city: Las Cruces
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state: New Mexico
city: Albany
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city: Brooklyn
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city: Olean
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city: Rochester
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city: Durham
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city: Greensboro
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city: Dayton
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city: Mayfield Village
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city: Duncansville
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city: Philadelphia
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city: West Reading
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city: Memphis
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state: Washington
city: Buenos Aires
country: Argentina
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city: Cordoba
country: Argentina
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city: Rosario
country: Argentina
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state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
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state: TUC
city: Buenos Aires
country: Argentina
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city: Ciudad de Buenos Aires
country: Argentina
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city: Quilmes
country: Argentina
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city: Rosario
country: Argentina
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city: San Juan
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
state: Brasil
city: Goiania
country: Brazil
facility: Research Site
state: GO
city: Curitiba
country: Brazil
facility: Research Site
state: PR
city: Sao Paulo
country: Brazil
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state: SP
city: St John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Pointe-claire
country: Canada
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state: Quebec
city: Rimouski
country: Canada
facility: Research Site
state: Quebec
city: Bruntal
country: Czech Republic
facility: Research Site
city: Ceske Budejovice
country: Czech Republic
facility: Research Site
city: Hlucin
country: Czech Republic
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city: Ostrava-trebovice
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Zlin
country: Czech Republic
facility: Research Site
city: Orleans Cedex 1
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
state: HH
city: Aachen
country: Germany
facility: Research Site
state: Nordrhein Westfalen
city: Leipzig
country: Germany
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state: SN
city: Erlangen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Muenchen
country: Germany
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city: Budapest
country: Hungary
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city: Ashkelon
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel-hashomer
country: Israel
facility: Research Site
city: Jesi
country: Italy
facility: Research Site
state: AN
city: Ferrara
country: Italy
facility: Research Site
state: FE
city: Obrergon
country: Mexico
facility: Research Site
state: SON
city: Chihuahua
country: Mexico
facility: Research Site
city: DF
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Saltillo
country: Mexico
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Stellenbosch
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
state: Berkshire
city: Warrington
country: United Kingdom
facility: Research Site
state: Cheshire
city: Maidstone
country: United Kingdom
facility: Research Site
state: Kent
city: Eastbourne
country: United Kingdom
facility: Research Site
state: Sussex
city: Cambridge
country: United Kingdom
facility: Research Site
city: Christchurch
country: United Kingdom
facility: Research Site
city: Ipswich
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Westcliff-on-the Sea
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Neil MacKillop, MD PhD
role: STUDY_DIRECTOR
References: