Clinical trial NCT01197521: Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Not Responding.
Official title: (OSKIRA-1): 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 an Inadequate Response to Methotrexate
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: 923
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 but not responding. The study will last for 1 year.

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 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
* Previous failure to respond to a TNF alpha antagonist, anakinra or previous treatment with other biological agent
* Severe renal impairment
* Neutropenia

Primary outcomes:
measure: Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo.
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo.
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: ACR20 - Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1
timeFrame: 1 week
measure: Proportion of Patients Achieving ACR50 up to Week 24
timeFrame: 24 weeks
measure: Proportion of Patients Achieving ACR70 up to Week 24
timeFrame: 24 weeks
measure: ACRn - Comparison Between Fostamatinib and Placebo at Week 24
timeFrame: 24 weeks
measure: Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12
timeFrame: 12 weeks
measure: Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24
timeFrame: 24 weeks
measure: Proportion of Patients Achieving DAS28-CRP EULAR Response at Week 24
timeFrame: 24 weeks
measure: HAQ-DI Response - Comparison of the Change (>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24
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: Tucson
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: Santa Maria
country: United States
facility: Research Site
state: California
city: Santa Monica
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: Lewes
country: United States
facility: Research Site
state: Delaware
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Springfield
country: United States
facility: Research Site
state: Illinois
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Bowling Green
country: United States
facility: Research Site
state: Kentucky
city: Flowood
country: United States
facility: Research Site
state: Mississippi
city: Florissant
country: United States
facility: Research Site
state: Missouri
city: Richmond Heights
country: United States
facility: Research Site
state: Missouri
city: St Louis
country: United States
facility: Research Site
state: Missouri
city: Kalispell
country: United States
facility: Research Site
state: Montana
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Albany
country: United States
facility: Research Site
state: New York
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Olean
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Perrysburg
country: United States
facility: Research Site
state: Ohio
city: Lake Oswego
country: United States
facility: Research Site
state: Oregon
city: Erie
country: United States
facility: Research Site
state: Pennsylvania
city: Waxford
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Hixson
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Mesquite
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Reading
country: Argentina
facility: Research Site
state: Berkshire
city: Buenos Aires
country: Argentina
facility: Research Site
state: Caba
city: Ciudad Autonoma Bs As
country: Argentina
facility: Research Site
state: CBA
city: Cordoba
country: Argentina
facility: Research Site
state: CRD
city: Rosario
country: Argentina
facility: Research Site
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
state: TUC
city: Caba
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Juan
country: Argentina
facility: Research Site
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Cairns
country: Australia
facility: Research Site
state: Queensland
city: Southport
country: Australia
facility: Research Site
state: Queensland
city: Brussels
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Vitoria
country: Brazil
facility: Research Site
state: ES
city: Recife
country: Brazil
facility: Research Site
state: PE
city: Curitiba
country: Brazil
facility: Research Site
state: PR
city: Sao Paulo
country: Brazil
facility: Research Site
state: SP
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Plovdiv
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: Osorno
country: Chile
facility: Research Site
state: X Region
city: Santiago
country: Chile
facility: Research Site
city: Parnu
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Orleans Cedex 1
country: France
facility: Research Site
city: Paris Cedex 13
country: France
facility: Research Site
city: Balatonfured
country: Hungary
facility: Research Site
city: Bekescsaba
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Mako
country: Hungary
facility: Research Site
city: Sopron
country: Hungary
facility: Research Site
city: Szentes
country: Hungary
facility: Research Site
city: Zalaegerszeg-pozva
country: Hungary
facility: Research Site
city: Secunderabad
country: India
facility: Research Site
state: Andhra Pradesh
city: Vishakhapatnam
country: India
facility: Research Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Bangalore
country: India
facility: Research Site
state: Karnataka
city: Mangalore
country: India
facility: Research Site
state: Karnataka
city: Udupi
country: India
facility: Research Site
state: Karnataka
city: Nagpur
country: India
facility: Research Site
state: Maharshtra
city: Lucknow
country: India
facility: Research Site
state: Uttar Pradesh
city: Calcutta
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Saltillo
country: Mexico
facility: Research Site
state: Coahuila
city: Mexico
country: Mexico
facility: Research Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Research Site
state: JAL
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo Leon
city: Obrergon
country: Mexico
facility: Research Site
state: SON
city: Chihuahua
country: Mexico
facility: Research Site
city: Mexicali
country: Mexico
facility: Research Site
city: San Luis Potosi
country: Mexico
facility: Research Site
city: Pueblo Libre
country: Peru
facility: Research Site
state: Lima
city: Arequipa
country: Peru
facility: Research Site
city: Lima
country: Peru
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: Katowice
country: Poland
facility: Research Site
city: Krakow
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: Bratislava
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Rimavska Sobota
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
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: Kiev
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Vinnytsya
country: Ukraine
facility: Research Site
city: Zaporyzhzhya
country: Ukraine
facility: Research Site
city: Warrington
country: United Kingdom
facility: Research Site
state: Cheshire
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: 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:
citation: Kjelgaard-Petersen CF, Platt A, Braddock M, Jenkins MA, Musa K, Graham E, Gantzel T, Slynn G, Weinblatt ME, Karsdal MA, Thudium CS, Bay-Jensen AC. Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis. Arthritis Rheumatol. 2018 Sep;70(9):1419-1428. doi: 10.1002/art.40527. Epub 2018 Jul 24.