Evaluation of Safety and Effectiveness of Fostamatinib Compared to Placebo in Patients in Asia With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01569074
• Other study ID #: D4300C00008
• Status: Terminated
• Phase: Phase 2
• First received: March 30, 2012
• Last updated: February 27, 2014
• Start date: April 2012
• Est. completion date: July 2013

Study information

• Verified date: February 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices AgencySouth Korea: Korea Food and Drug Administration (KFDA)Hong Kong: Department of HealthTaiwan: Department of HealthVietnam: Ministry of HealthThailand: Food and Drug AdministrationChina: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 163
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Fostamatinib
Fostamatinib 100mg twice daily for 12 weeks
• Fostamatinib
Fostamatinib 100mg twice daily for 4 weeks, followed by150mg once daily up to Week 12
• Fostamatinib
Fostamatinib 75mg twice daily for 12 weeks
• Fostamatinib
Fostamatinib 50mg twice daily for 12 weeks
• Placebo
Placebo twice daily for 12 weeks

Locations

Country	Name	City	State
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	New Territories	HK
Japan	Research Site	Fukuoka-shi	Fukuoka
Japan	Research Site	Hamamatsu-shi	Shizuoka
Japan	Research Site	Isahaya	Nagasaki
Japan	Research Site	Itabashi	Tokyo
Japan	Research Site	Kasama-shi	Ibaraki
Japan	Research Site	Kato-shi	Hyogo
Japan	Research Site	Kitakyushu-shi	Fukuoka
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kurume	Fukuoka
Japan	Research Site	Matsue-shi	Shimane
Japan	Research Site	Matsuyama	Ehime
Japan	Research Site	Nagasaki
Japan	Research Site	Nagasaki-shi	Nagasaki
Japan	Research Site	Okayama-shi	Okayama
Japan	Research Site	Omura-shi	Nagasaki
Japan	Research Site	Sapporo	Hokkaido
Japan	Research Site	Sasebo-shi	Nagasaki
Japan	Research Site	Sendai	Miyagi
Japan	Research Site	Shibata	Niigata
Japan	Research Site	Shinjuku	Tokyo
Japan	Research Site	Tomigusuku-shi	Okinawa
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
Taiwan	Research Site	Chiayi
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Thailand	Research Site	Bangkok
Thailand	Research Site	Singapore
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Hong Kong,  Japan,  Korea, Republic of,  Taiwan,  Thailand,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No