Evaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis (OSKIRA-Asia-1)

This study has been terminated.
(AZ decision to discontinue fostamatinib development in RA; rights to fostamatinib returned to Rigel Pharmaceuticals.)
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01569074
First received: March 30, 2012
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Fostamatinib
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Proportion of Patients Achieving ACR20 at Week 12, Comparison Between Fostamatinib and Placebo [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 163
Study Start Date: April 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dosing A regimen
Oral treatment
Drug: Fostamatinib
Fostamatinib 100mg twice daily for 12 weeks
Experimental: Dosing B regimen
Oral treatment
Drug: Fostamatinib
Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12
Experimental: Dosing C regimen
Oral treatment
Drug: Fostamatinib
Fostamatinib 75mg twice daily for 12 weeks
Experimental: Dosign D regimen
Oral treatment
Drug: Fostamatinib
Fostamatinib 50mg twice daily for 12 weeks
Placebo Comparator: Dosing E regimen
Oral treatment
Drug: Placebo
Placebo twice daily 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01569074

Locations
Hong Kong
Research Site
New Territories, HK, Hong Kong
Research Site
Hong Kong, Hong Kong
Japan
Research Site
Matsuyama, Ehime, Japan
Research Site
Fukuoka-shi, Fukuoka, Japan
Research Site
Kitakyushu-shi, Fukuoka, Japan
Research Site
Kurume, Fukuoka, Japan
Research Site
Sapporo, Hokkaido, Japan
Research Site
Kato-shi, Hyogo, Japan
Research Site
Kasama-shi, Ibaraki, Japan
Research Site
Kumamoto-shi, Kumamoto, Japan
Research Site
Sendai, Miyagi, Japan
Research Site
Isahaya, Nagasaki, Japan
Research Site
Nagasaki-shi, Nagasaki, Japan
Research Site
Omura-shi, Nagasaki, Japan
Research Site
Sasebo-shi, Nagasaki, Japan
Research Site
Shibata, Niigata, Japan
Research Site
Okayama-shi, Okayama, Japan
Research Site
Tomigusuku-shi, Okinawa, Japan
Research Site
Matsue-shi, Shimane, Japan
Research Site
Hamamatsu-shi, Shizuoka, Japan
Research Site
Itabashi, Tokyo, Japan
Research Site
Shinjuku, Tokyo, Japan
Research Site
Nagasaki, Japan
Korea, Republic of
Research Site
Anyang-si, Gyeonggi-do, Korea, Republic of
Research Site
Gwangju, Korea, Republic of
Research Site
Incheon, Korea, Republic of
Research Site
Seoul, Korea, Republic of
Taiwan
Research Site
Chiayi, Taiwan
Research Site
Kaohsiung, Taiwan
Research Site
Taichung, Taiwan
Research Site
Taipei, Taiwan
Thailand
Research Site
Bangkok, Thailand
Research Site
Singapore, Thailand
Vietnam
Research Site
Hanoi, Vietnam
Research Site
Ho Chi Minh, Vietnam
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Neil - Mackillop, MD AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01569074     History of Changes
Other Study ID Numbers: D4300C00008
Study First Received: March 30, 2012
Results First Received: November 21, 2013
Last Updated: February 27, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
South Korea: Korea Food and Drug Administration (KFDA)
Hong Kong: Department of Health
Taiwan: Department of Health
Vietnam: Ministry of Health
Thailand: Food and Drug Administration
China: Food and Drug Administration

Keywords provided by AstraZeneca:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014