Clinical trial NCT01264770: Evaluation of Efficacy and Safety of Fostamatinib Monotherapy Compared With Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (RA)
Official title: (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 Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
OSKIRA
fostamatinib
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-12-22
Enrollment: 644
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 improvements in signs and symptoms of rheumatoid arthritis (RA) for fostamatinib compared to placebo or adalimumab in patients who are Disease-Modifying anti-rheumatic drug (DMARD) naïve, DMARD intolerant or have had an inadequate response to DMARDs. The study will last for approximately six months

Detailed description: Sub-study:

Full title: Optional Genetic Research

Date: 10 September 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 adalimumab; and/or susceptibility to, progression of and prognosis of RA

The main study recruitment is complete, and sub study recruitment will continue until the target is reached, estimated to be June 2013

Sub-study:

Full title: (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 and 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) 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 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)

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

Primary outcomes:
measure: DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo
timeFrame: Baseline and 6 weeks
measure: DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: DAS28 EULAR Response at Week 6
timeFrame: 6 weeks
measure: DAS28 EULAR Response at Week 24
timeFrame: 24 weeks
measure: Proportion of Patients Achieving ACR20 up to Week 24
timeFrame: 6 and 24 weeks
measure: Proportion of Patients Achieving ACR50 up to Week 24
timeFrame: 6 and 24 weeks
measure: Proportion of Patients Achieving ACR70 up to Week 24
timeFrame: 6 and 24 weeks
measure: ACRn - Comparison Between Fostamatinib and Placebo at Week 6
timeFrame: Baseline and 6 weeks
measure: ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24
timeFrame: Baseline and 24 weeks
measure: HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6
timeFrame: Baseline and 6 weeks
measure: HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24
timeFrame: Baseline and 24 weeks
measure: SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24
timeFrame: Baseline and 24 weeks
measure: SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Glendale
country: United States
facility: Research Site
state: Arizona
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Bridgeport
country: United States
facility: Research Site
state: Connecticut
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Palm Harbor
country: United States
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state: Florida
city: Pinellas Park
country: United States
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state: Florida
city: Venice
country: United States
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state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: South Bend
country: United States
facility: Research Site
state: Indiana
city: Bowling Green
country: United States
facility: Research Site
state: Kentucky
city: Elizabethtown
country: United States
facility: Research Site
state: Kentucky
city: Oxon Hill
country: United States
facility: Research Site
state: Maryland
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Richmond Heights
country: United States
facility: Research Site
state: Missouri
city: Kalispell
country: United States
facility: Research Site
state: Montana
city: Nashua
country: United States
facility: Research Site
state: New Hampshire
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Las Cruces
country: United States
facility: Research Site
state: New Mexico
city: Brooklyn
country: United States
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state: New York
city: Charlotte
country: United States
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state: North Carolina
city: Perrysburg
country: United States
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state: Ohio
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Jackson
country: United States
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state: Tennessee
city: Knoxville
country: United States
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state: Tennessee
city: Memphis
country: United States
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state: Tennessee
city: Austin
country: United States
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state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Mesquite
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Pleven
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sevlievo
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Veliko Tarnovo
country: Bulgaria
facility: Research Site
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Brno
country: Czech Republic
facility: Research Site
city: Bruntal
country: Czech Republic
facility: Research Site
city: Hlucin
country: Czech Republic
facility: Research Site
city: Liberec
country: Czech Republic
facility: Research Site
city: Ostrava - Poruba
country: Czech Republic
facility: Research Site
city: Ostrava - Trebovice
country: Czech Republic
facility: Research Site
city: Ostrava
country: Czech Republic
facility: Research Site
city: Praha 11
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Praha 4
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Zlin
country: Czech Republic
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Balatonfured
country: Hungary
facility: Research Site
city: Balatonfüred
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Bytom
country: Poland
facility: Research Site
city: Chelm Slaski
country: Poland
facility: Research Site
city: Grodzisk Mazowiecki
country: Poland
facility: Research Site
city: Sroda Wielkopolska
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zyrardow
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhny Novgorod
country: Russian Federation
facility: Research Site
city: Petrozavodsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Trebisov
country: Slovakia
facility: Research Site
city: Trnava
country: Slovakia
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
state: Gauteng
city: Durban
country: South Africa
facility: Research Site
state: Kwazulu Natal
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Cape Town
country: South Africa
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: Donetsk
country: Ukraine
facility: Research Site
city: Ivano-frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Simferopol
country: Ukraine
facility: Research Site
city: Zaporyzhzhya
country: Ukraine
facility: Research Site
city: Reading
country: United Kingdom
facility: Research Site
state: Berkshire
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Eastbourne
country: United Kingdom
facility: Research Site
state: Sussex
city: Basingstoke
country: United Kingdom
facility: Research Site
city: Eastbourne
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Neil MacKillop, MD PhD
role: STUDY_DIRECTOR
References:
citation: Taylor PC, Genovese MC, Greenwood M, Ho M, Nasonov E, Oemar B, Stoilov R, Vencovsky J, Weinblatt M. OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy. Ann Rheum Dis. 2015 Dec;74(12):2123-9. doi: 10.1136/annrheumdis-2014-205361. Epub 2014 Jul 29.