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. (OSKIRA - 1)

February 27, 2014 updated by: AstraZeneca

(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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

923

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Caba, Argentina
        • Research Site
      • Quilmes, Argentina
        • Research Site
      • San Juan, Argentina
        • Research Site
    • Berkshire
      • Reading, Berkshire, Argentina
        • Research Site
    • CBA
      • Ciudad Autonoma Bs As, CBA, Argentina
        • Research Site
    • CRD
      • Cordoba, CRD, Argentina
        • Research Site
    • Caba
      • Buenos Aires, Caba, Argentina
        • Research Site
    • Santa Fe
      • Rosario, Santa Fe, Argentina
        • Research Site
    • TUC
      • San Miguel de Tucuman, TUC, Argentina
        • Research Site
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia
        • Research Site
    • Queensland
      • Cairns, Queensland, Australia
        • Research Site
      • Southport, Queensland, Australia
        • Research Site
  • Belgium
      • Brussels, Belgium
        • Research Site
      • Yvoir, Belgium
        • Research Site
  • Brazil
      • Rio de Janeiro, Brazil
        • Research Site
    • ES
      • Vitoria, ES, Brazil
        • Research Site
    • PE
      • Recife, PE, Brazil
        • Research Site
    • PR
      • Curitiba, PR, Brazil
        • Research Site
    • SP
      • Sao Paulo, SP, Brazil
        • Research Site
  • Bulgaria
      • Plovdiv, Bulgaria
        • Research Site
      • Sevlievo, Bulgaria
        • Research Site
      • Sofia, Bulgaria
        • Research Site
      • Veliko Tarnovo, Bulgaria
        • Research Site
  • Chile
      • Santiago, Chile
        • Research Site
    • X Region
      • Osorno, X Region, Chile
        • Research Site
  • Estonia
      • Parnu, Estonia
        • Research Site
      • Tallinn, Estonia
        • Research Site
      • Tartu, Estonia
        • Research Site
  • France
      • Orleans Cedex 1, France
        • Research Site
      • Paris Cedex 13, France
        • Research Site
  • Hungary
      • Balatonfured, Hungary
        • Research Site
      • Bekescsaba, Hungary
        • Research Site
      • Budapest, Hungary
        • Research Site
      • Debrecen, Hungary
        • Research Site
      • Mako, Hungary
        • Research Site
      • Sopron, Hungary
        • Research Site
      • Szentes, Hungary
        • Research Site
      • Zalaegerszeg-pozva, Hungary
        • Research Site
  • India
      • Calcutta, India
        • Research Site
      • Hyderabad, India
        • Research Site
    • Andhra Pradesh
      • Secunderabad, Andhra Pradesh, India
        • Research Site
      • Vishakhapatnam, Andhra Pradesh, India
        • Research Site
    • Gujarat
      • Ahmedabad, Gujarat, India
        • Research Site
    • Karnataka
      • Bangalore, Karnataka, India
        • Research Site
      • Mangalore, Karnataka, India
        • Research Site
      • Udupi, Karnataka, India
        • Research Site
    • Maharshtra
      • Nagpur, Maharshtra, India
        • Research Site
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India
        • Research Site
  • Mexico
      • Chihuahua, Mexico
        • Research Site
      • Mexicali, Mexico
        • Research Site
      • San Luis Potosi, Mexico
        • Research Site
    • Coahuila
      • Saltillo, Coahuila, Mexico
        • Research Site
    • Distrito Federal
      • Mexico, Distrito Federal, Mexico
        • Research Site
    • JAL
      • Guadalajara, JAL, Mexico
        • Research Site
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico
        • Research Site
    • SON
      • Obrergon, SON, Mexico
        • Research Site
  • Peru
      • Arequipa, Peru
        • Research Site
      • Lima, Peru
        • Research Site
    • Lima
      • Pueblo Libre, Lima, Peru
        • Research Site
  • Poland
      • Bytom, Poland
        • Research Site
      • Chelm Slaski, Poland
        • Research Site
      • Grodzisk Mazowiecki, Poland
        • Research Site
      • Katowice, Poland
        • Research Site
      • Krakow, Poland
        • Research Site
      • Warszawa, Poland
        • Research Site
      • Wroclaw, Poland
        • Research Site
      • Zyrardow, Poland
        • Research Site
  • Slovakia
      • Bratislava, Slovakia
        • Research Site
      • Poprad, Slovakia
        • Research Site
      • Rimavska Sobota, Slovakia
        • Research Site
      • Zilina, Slovakia
        • Research Site
  • Ukraine
      • Donetsk, Ukraine
        • Research Site
      • Ivano-frankivsk, Ukraine
        • Research Site
      • Kharkiv, Ukraine
        • Research Site
      • Kiev, Ukraine
        • Research Site
      • Kyiv, Ukraine
        • Research Site
      • Lviv, Ukraine
        • Research Site
      • Odessa, Ukraine
        • Research Site
      • Vinnytsya, Ukraine
        • Research Site
      • Zaporyzhzhya, Ukraine
        • Research Site
  • United Kingdom
      • Christchurch, United Kingdom
        • Research Site
      • Ipswich, United Kingdom
        • Research Site
      • London, United Kingdom
        • Research Site
      • Westcliff-on-the Sea, United Kingdom
        • Research Site
      • Wirral, United Kingdom
        • Research Site
    • Cheshire
      • Warrington, Cheshire, United Kingdom
        • Research Site
  • United States
    • Alabama
      • Anniston, Alabama, United States
        • Research Site
      • Huntsville, Alabama, United States
        • Research Site
      • Tuscaloosa, Alabama, United States
        • Research Site
    • Arizona
      • Tucson, Arizona, United States
        • Research Site
    • California
      • Huntington Beach, California, United States
        • Research Site
      • Long Beach, California, United States
        • Research Site
      • Santa Maria, California, United States
        • Research Site
      • Santa Monica, California, United States
        • Research Site
    • Colorado
      • Colorado Springs, Colorado, United States
        • Research Site
    • Connecticut
      • Bridgeport, Connecticut, United States
        • Research Site
    • Delaware
      • Lewes, Delaware, United States
        • Research Site
    • Florida
      • Daytona Beach, Florida, United States
        • Research Site
      • Ocala, Florida, United States
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States
        • Research Site
      • Marietta, Georgia, United States
        • Research Site
    • Idaho
      • Idaho Falls, Idaho, United States
        • Research Site
    • Illinois
      • Springfield, Illinois, United States
        • Research Site
    • Kansas
      • Wichita, Kansas, United States
        • Research Site
    • Kentucky
      • Bowling Green, Kentucky, United States
        • Research Site
    • Mississippi
      • Flowood, Mississippi, United States
        • Research Site
    • Missouri
      • Florissant, Missouri, United States
        • Research Site
      • Richmond Heights, Missouri, United States
        • Research Site
      • St Louis, Missouri, United States
        • Research Site
    • Montana
      • Kalispell, Montana, United States
        • Research Site
    • New Mexico
      • Albuquerque, New Mexico, United States
        • Research Site
    • New York
      • Albany, New York, United States
        • Research Site
      • Brooklyn, New York, United States
        • Research Site
      • Olean, New York, United States
        • Research Site
    • North Carolina
      • Asheville, North Carolina, United States
        • Research Site
      • Greensboro, North Carolina, United States
        • Research Site
    • Ohio
      • Perrysburg, Ohio, United States
        • Research Site
    • Oregon
      • Lake Oswego, Oregon, United States
        • Research Site
    • Pennsylvania
      • Erie, Pennsylvania, United States
        • Research Site
      • Waxford, Pennsylvania, United States
        • Research Site
    • South Carolina
      • Charleston, South Carolina, United States
        • Research Site
    • Tennessee
      • Hixson, Tennessee, United States
        • Research Site
      • Memphis, Tennessee, United States
        • Research Site
    • Texas
      • Dallas, Texas, United States
        • Research Site
      • Houston, Texas, United States
        • Research Site
      • Mesquite, Texas, United States
        • Research Site
      • San Antonio, Texas, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dosing Regimen A
Oral Treatment
Drug: fostamatinib
fostamatinib 100 mg twice daily
Drug: fostamatinib
fostamatinib 100 mg twice daily/150 mg once daily
Experimental: Dosing Regimen B
Oral Treatment
Drug: fostamatinib
fostamatinib 100 mg twice daily
Drug: fostamatinib
fostamatinib 100 mg twice daily/150 mg once daily
Placebo Comparator: Dosing Regimen C
Oral Treatment
Drug: placebo, fostamatinib
Placebo for 24 weeks followed by fostamatinib 100 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo.
Time Frame: 24 weeks
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.
24 weeks
Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo.
Time Frame: Baseline and 24 weeks
mTSS: modified total Sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, PO=orally, QD=once a day.
Baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACR20 - Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1
Time Frame: 1 week
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally.
1 week
Proportion of Patients Achieving ACR50 up to Week 24
Time Frame: 24 weeks
ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.
24 weeks
Proportion of Patients Achieving ACR70 up to Week 24
Time Frame: 24 weeks
ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.
24 weeks
ACRn - Comparison Between Fostamatinib and Placebo at Week 24
Time Frame: 24 weeks
ACRn: American College of Rheumatology index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints), or in blood test measures of inflammation (such as CRP) or the physician or patient's own assessments of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. BID=twice daily, CI=confidence interval, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, PO=orally, QD=once a day, RA=rheumatoid arthritis. Mean refers to change at Week 24.
24 weeks
Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12
Time Frame: 12 weeks
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. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, OR=odds ratio, PO=orally, QD=once a day.
12 weeks
Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24
Time Frame: 24 weeks
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. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID=twice daily, CRP=C-reactive protein, DMARD=Disease-modifying anti-rheumatic drug, OR=odds ratio, PO=orally, QD=once a day.
24 weeks
Proportion of Patients Achieving DAS28-CRP EULAR Response at Week 24
Time Frame: 24 weeks
Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DAS28=Disease Activity Score based on a 28-joint count, DMARD=disease-modifying anti-rheumatic drug, OR=odds ratio, PO=orally, QD=once a day.
24 weeks
HAQ-DI Response - Comparison of the Change (>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24
Time Frame: Baseline and 24 weeks
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with higher score indicating greater disability. HAQ-DI response: a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, OR=odds ratio, PO=orally, QD=once a day.
Baseline and 24 weeks
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24
Time Frame: Baseline and 24 weeks
SF-36: 36 item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical Component Scores (PCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease modifying antirheumatic drug, PO=orally, QD=once daily, QoL=quality of life.
Baseline and 24 weeks
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24
Time Frame: Baseline and 24 weeks
SF-36: 36 item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality, Social Function, Role-emotional & Mental Health) are derived & normalised to a scale of 0-100. Mental Component Scores (MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease modifying antirheumatic drug, PO=orally, QD=once daily, QoL=quality of life.
Baseline and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Study Director: Neil MacKillop, MD PhD, AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

September 8, 2010

First Submitted That Met QC Criteria

September 8, 2010

First Posted (Estimate)

September 9, 2010

Study Record Updates

Last Update Posted (Estimate)

April 7, 2014

Last Update Submitted That Met QC Criteria

February 27, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4300C00001
  • 2010-020743-12 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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