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

(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

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Fostamatinib; Drug: Fostamatinib; Drug: Fostamatinib; Drug: Fostamatinib; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

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:

• 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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dosing A regimen; Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12; Drug: Fostamatinib; Fostamatinib 75mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 50mg twice daily for 12 weeks
Experimental: Dosing B regimen; Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12; Drug: Fostamatinib; Fostamatinib 75mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 50mg twice daily for 12 weeks
Experimental: Dosing C regimen; Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12; Drug: Fostamatinib; Fostamatinib 75mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 50mg twice daily for 12 weeks
Experimental: Dosign D regimen; Oral treatment	Drug: Fostamatinib; Fostamatinib 100mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12; Drug: Fostamatinib; Fostamatinib 75mg twice daily for 12 weeks; Drug: Fostamatinib; Fostamatinib 50mg twice daily for 12 weeks
Placebo Comparator: Dosing E regimen; Oral treatment	Drug: Placebo; Placebo twice daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 week
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.	12 weeks
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.	12 weeks
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.	Baseline and 12 weeks
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.	12 weeks
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.	12 weeks
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.	12 weeks
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.	Baseline and 12 weeks
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.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Neil - MacKillop, MD, AstraZeneca

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: March 30, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (Estimate): April 2, 2012

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: Rheumatoid Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: D4300C00008