(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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 923
- Locations
- 1
- Primary Endpoint
- Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo.
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Dosing Regimen A
Oral Treatment
Intervention: fostamatinib (Drug)
Dosing Regimen B
Oral Treatment
Intervention: fostamatinib (Drug)
Dosing Regimen C
Oral Treatment
Intervention: placebo, fostamatinib (Drug)
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- ACR20 - Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1(1 week)
- Proportion of Patients Achieving ACR50 up to Week 24(24 weeks)
- Proportion of Patients Achieving ACR70 up to Week 24(24 weeks)
- ACRn - Comparison Between Fostamatinib and Placebo at Week 24(24 weeks)
- Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12(12 weeks)
- Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24(24 weeks)
- Proportion of Patients Achieving DAS28-CRP EULAR Response at Week 24(24 weeks)
- HAQ-DI Response - Comparison of the Change (>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24(Baseline and 24 weeks)
- SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24(Baseline and 24 weeks)
- SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24(Baseline and 24 weeks)