Evaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis
- Registration Number
- NCT01569074
- Lead Sponsor
- AstraZeneca
- Brief Summary
The purpose of the study is to evaluate the effectiveness of four 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 12 weeks.
- Detailed Description
(OSKIRA-Asia-1): A Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose Ranging Study in Asia Evaluating Efficacy and Safety of Fostamatinib in Patients with Active Rheumatoid Arthritis who are Inadequate Responders to Methotrexate Therapy
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 163
- Male or female aged 18 and over
- Active rheumatoid arthritis (RA) diagnosed after the age of 16
- 6 or more swollen joints and 6 or more tender/painful joints from certain joints in the hands, wrists, arms and knees
- At least one of: positive result for rheumatoid factor test, either in the past or currently (blood test); x-ray showing bone erosion within the last 12 months; presence of certain antibodies in the blood (blood test)
- Currently taking methotrexate for at least 4 months (and on a stable dose for at least 6 weeks)
- Females who are pregnant or breast feeding
- Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders.
- Previously taken, but not responded to, certain biological treatments for rheumatoid arthritis
- High blood pressure that is not controlled by medication
- Low levels of neutrophils in the blood (blood test).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dosing A regimen Fostamatinib Oral treatment Dosing B regimen Fostamatinib Oral treatment Dosing C regimen Fostamatinib Oral treatment Dosign D regimen Fostamatinib Oral treatment Dosing E regimen Placebo Oral treatment
- Primary Outcome Measures
Name Time Method Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo 12 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 C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
- Secondary Outcome Measures
Name Time Method Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo 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 C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally.
Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo 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. DAS28-CRP score of \<=3.2 indicates low disease activity. BID = twice daily, CRP = C-reactive protein, , DMARD = disease modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once daily.
Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo 12 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 C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo 12 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 C-Reactive Protein) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
ACRn - Comparison Between Fostamatinib and Placebo at Week 12 Baseline and 12 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 C-Reactive Protein) 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. Mean refers to change at Week 12. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo 12 weeks Change from baseline in DAS28-CRP at Week 12 was derived and categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice a day, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo 12 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 is 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.
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12 Baseline and 12 weeks SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12 Baseline and 12 weeks SF-36 = 36-item Short Form Health Survey, as a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0 to 100. The physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50, standard deviation of 10. A higher score represents better quality of life. Mean changes from baseline are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Mean refers to change in scores at Week 12. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam