Back to resultsEvaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis (OSKIRA-Asia-1)
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fostamatinib
Fostamatinib
Fostamatinib
Fostamatinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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).
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Dosing A regimen
Dosing B regimen
Dosing C regimen
Dosign D regimen
Dosing E regimen
Arm Description
Oral treatment
Oral treatment
Oral treatment
Oral treatment
Oral treatment
Outcomes
Primary Outcome Measures
Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo
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
Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo
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 ACR50 at Week 12, Comparison Between Fostamatinib and Placebo
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
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
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 Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo
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 With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01569074
Brief Title
Evaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis
Acronym
OSKIRA-Asia-1
Official Title
(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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Terminated
Why Stopped
AZ decision to discontinue fostamatinib development in RA; rights to fostamatinib returned to Rigel Pharmaceuticals.
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
163 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dosing A regimen
Arm Type
Experimental
Arm Description
Oral treatment
Arm Title
Dosing B regimen
Arm Type
Experimental
Arm Description
Oral treatment
Arm Title
Dosing C regimen
Arm Type
Experimental
Arm Description
Oral treatment
Arm Title
Dosign D regimen
Arm Type
Experimental
Arm Description
Oral treatment
Arm Title
Dosing E regimen
Arm Type
Placebo Comparator
Arm Description
Oral treatment
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib 100mg twice daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib 75mg twice daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Fostamatinib
Intervention Description
Fostamatinib 50mg twice daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo twice daily for 12 weeks
Primary Outcome Measure Information:
Title
Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of Patients Achieving ACR20 at Week 1, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
1 week
Title
Proportion of Patients Achieving ACR50 at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Title
Proportion of Patients Achieving ACR70 at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Title
ACRn - Comparison Between Fostamatinib and Placebo at Week 12
Description
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.
Time Frame
Baseline and 12 weeks
Title
Proportion of Patients Achieving DAS28-CRP<=3.2 at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Title
Proportion of Patients With DAS28-CRP EULAR Response at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Title
Proportion of Patients With HAQ-DI Response at Week 12, Comparison Between Fostamatinib and Placebo
Description
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.
Time Frame
12 weeks
Title
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 12
Description
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.
Time Frame
Baseline and 12 weeks
Title
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 12
Description
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.
Time Frame
Baseline and 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil - Mackillop, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
New Territories
State/Province
HK
Country
Hong Kong
Facility Name
Research Site
City
Hong Kong
Country
Hong Kong
Facility Name
Research Site
City
Matsuyama
State/Province
Ehime
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
State/Province
Fukuoka
Country
Japan
Facility Name
Research Site
City
Kitakyushu-shi
State/Province
Fukuoka
Country
Japan
Facility Name
Research Site
City
Kurume
State/Province
Fukuoka
Country
Japan
Facility Name
Research Site
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Research Site
City
Kato-shi
State/Province
Hyogo
Country
Japan
Facility Name
Research Site
City
Kasama-shi
State/Province
Ibaraki
Country
Japan
Facility Name
Research Site
City
Kumamoto-shi
State/Province
Kumamoto
Country
Japan
Facility Name
Research Site
City
Sendai
State/Province
Miyagi
Country
Japan
Facility Name
Research Site
City
Isahaya
State/Province
Nagasaki
Country
Japan
Facility Name
Research Site
City
Nagasaki-shi
State/Province
Nagasaki
Country
Japan
Facility Name
Research Site
City
Omura-shi
State/Province
Nagasaki
Country
Japan
Facility Name
Research Site
City
Sasebo-shi
State/Province
Nagasaki
Country
Japan
Facility Name
Research Site
City
Shibata
State/Province
Niigata
Country
Japan
Facility Name
Research Site
City
Okayama-shi
State/Province
Okayama
Country
Japan
Facility Name
Research Site
City
Tomigusuku-shi
State/Province
Okinawa
Country
Japan
Facility Name
Research Site
City
Matsue-shi
State/Province
Shimane
Country
Japan
Facility Name
Research Site
City
Hamamatsu-shi
State/Province
Shizuoka
Country
Japan
Facility Name
Research Site
City
Itabashi
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Shinjuku
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Nagasaki
Country
Japan
Facility Name
Research Site
City
Anyang-si
State/Province
Gyeonggi-do
Country
Korea, Republic of
Facility Name
Research Site
City
Gwangju
Country
Korea, Republic of
Facility Name
Research Site
City
Incheon
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Chiayi
Country
Taiwan
Facility Name
Research Site
City
Kaohsiung
Country
Taiwan
Facility Name
Research Site
City
Taichung
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan
Facility Name
Research Site
City
Bangkok
Country
Thailand
Facility Name
Research Site
City
Singapore
Country
Thailand
Facility Name
Research Site
City
Hanoi
Country
Vietnam
Facility Name
Research Site
City
Ho Chi Minh
Country
Vietnam
12. IPD Sharing Statement
Citations:
PubMed Identifier
33254235
Citation
Tanaka Y, Millson D, Iwata S, Nakayamada S. Safety and efficacy of fostamatinib in rheumatoid arthritis patients with an inadequate response to methotrexate in phase II OSKIRA-ASIA-1 and OSKIRA-ASIA-1X study. Rheumatology (Oxford). 2021 Jun 18;60(6):2884-2895. doi: 10.1093/rheumatology/keaa732.
Results Reference
derived
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Evaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis
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