Rheumatoid Arthritis Clinical Trial
— OSKIRA -4Official title:
(OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared With Adalimumab Monotherapy in Patients With Active Rheumatoid Arthritis
The purpose of the study is to evaluate the improvements in signs and symptoms of rheumatoid arthritis (RA) for fostamatinib compared to placebo or adalimumab in patients who are Disease-Modifying anti-rheumatic drug (DMARD) naïve, DMARD intolerant or have had an inadequate response to DMARDs. The study will last for approximately six months
Status | Terminated |
Enrollment | 644 |
Est. completion date | August 2013 |
Est. primary completion date | October 2012 |
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 and diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs - 4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count) and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Protein (CRP) blood result of 10mg/L or more - At least 2 of the following: documented history or current presence of positive rheumatoid factor (blood test), radiographic erosion within 12 months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test) Exclusion Criteria: - Females who are pregnant or breast feeding - Poorly controlled hypertension - Liver disease or significant liver function test abnormalities - Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders - Recent or significant cardiovascular disease - Significant active or recent infection including tuberculosis - Previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab - Use of any DMARDs within 6 weeks before first study visit - Severe renal impairment - Neutropenia |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Bulgaria | Research Site | Pleven | |
Bulgaria | Research Site | Plovdiv | |
Bulgaria | Research Site | Ruse | |
Bulgaria | Research Site | Sevlievo | |
Bulgaria | Research Site | Sofia | |
Bulgaria | Research Site | Veliko Tarnovo | |
Canada | Research Site | Mississauga | Ontario |
Czech Republic | Research Site | Brno | |
Czech Republic | Research Site | Bruntal | |
Czech Republic | Research Site | Hlucin | |
Czech Republic | Research Site | Liberec | |
Czech Republic | Research Site | Ostrava | |
Czech Republic | Research Site | Ostrava - Poruba | |
Czech Republic | Research Site | Ostrava - Trebovice | |
Czech Republic | Research Site | Praha | |
Czech Republic | Research Site | Praha 11 | |
Czech Republic | Research Site | Praha 2 | |
Czech Republic | Research Site | Praha 4 | |
Czech Republic | Research Site | Zlin | |
Germany | Research Site | Dresden | |
Germany | Research Site | Hamburg | |
Germany | Research Site | Muenchen | |
Hungary | Research Site | Balatonfured | |
Hungary | Research Site | Balatonfüred | |
Hungary | Research Site | Budapest | |
Hungary | Research Site | Debrecen | |
Hungary | Research Site | Zalaegerszeg | |
Netherlands | Research Site | Amsterdam | |
Poland | Research Site | Bytom | |
Poland | Research Site | Chelm Slaski | |
Poland | Research Site | Grodzisk Mazowiecki | |
Poland | Research Site | Lódz | |
Poland | Research Site | Sroda Wielkopolska | |
Poland | Research Site | Warszawa | |
Poland | Research Site | Wroclaw | |
Poland | Research Site | Zyrardow | |
Russian Federation | Research Site | Moscow | |
Russian Federation | Research Site | Nizhny Novgorod | |
Russian Federation | Research Site | Petrozavodsk | |
Russian Federation | Research Site | Ryazan | |
Russian Federation | Research Site | St. Petersburg | |
Russian Federation | Research Site | Voronezh | |
Russian Federation | Research Site | Yaroslavl | |
Slovakia | Research Site | Trebisov | |
Slovakia | Research Site | Trnava | |
South Africa | Research Site | Cape Town | Western Cape |
South Africa | Research Site | Cape Town | |
South Africa | Research Site | Durban | |
South Africa | Research Site | Durban | Kwazulu Natal |
South Africa | Research Site | Pretoria | |
South Africa | Research Site | Pretoria | Gauteng |
South Africa | Research Site | Stellenbosch | |
Ukraine | Research Site | Donetsk | |
Ukraine | Research Site | Ivano-frankivsk | |
Ukraine | Research Site | Kharkiv | |
Ukraine | Research Site | Kyiv | |
Ukraine | Research Site | Lutsk | |
Ukraine | Research Site | Lviv | |
Ukraine | Research Site | Odessa | |
Ukraine | Research Site | Simferopol | |
Ukraine | Research Site | Zaporyzhzhya | |
United Kingdom | Research Site | Basingstoke | |
United Kingdom | Research Site | Eastbourne | |
United Kingdom | Research Site | Eastbourne | Sussex |
United Kingdom | Research Site | London | Greater London |
United Kingdom | Research Site | London | |
United Kingdom | Research Site | Manchester | |
United Kingdom | Research Site | Reading | Berkshire |
United Kingdom | Research Site | Wolverhampton | |
United States | Research Site | Albuquerque | New Mexico |
United States | Research Site | Austin | Texas |
United States | Research Site | Birmingham | Alabama |
United States | Research Site | Bowling Green | Kentucky |
United States | Research Site | Bridgeport | Connecticut |
United States | Research Site | Brooklyn | New York |
United States | Research Site | Charlotte | North Carolina |
United States | Research Site | Chicago | Illinois |
United States | Research Site | Colorado Springs | Colorado |
United States | Research Site | Daytona Beach | Florida |
United States | Research Site | Duncansville | Pennsylvania |
United States | Research Site | Elizabethtown | Kentucky |
United States | Research Site | Glendale | Arizona |
United States | Research Site | Greenville | South Carolina |
United States | Research Site | Houston | Texas |
United States | Research Site | Huntington Beach | California |
United States | Research Site | Jackson | Tennessee |
United States | Research Site | Jacksonville | Florida |
United States | Research Site | Kalamazoo | Michigan |
United States | Research Site | Kalispell | Montana |
United States | Research Site | Knoxville | Tennessee |
United States | Research Site | Las Cruces | New Mexico |
United States | Research Site | Long Beach | California |
United States | Research Site | Memphis | Tennessee |
United States | Research Site | Mesa | Arizona |
United States | Research Site | Mesquite | Texas |
United States | Research Site | Miami | Florida |
United States | Research Site | Nashua | New Hampshire |
United States | Research Site | Ocala | Florida |
United States | Research Site | Oxon Hill | Maryland |
United States | Research Site | Palm Harbor | Florida |
United States | Research Site | Perrysburg | Ohio |
United States | Research Site | Phoenix | Arizona |
United States | Research Site | Pinellas Park | Florida |
United States | Research Site | Plano | Texas |
United States | Research Site | Richmond Heights | Missouri |
United States | Research Site | San Antonio | Texas |
United States | Research Site | Scottsdale | Arizona |
United States | Research Site | South Bend | Indiana |
United States | Research Site | Venice | Florida |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
United States, Bulgaria, Canada, Czech Republic, Germany, Hungary, Netherlands, Poland, Russian Federation, Slovakia, South Africa, Ukraine, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | DAS28-CRP Score - Change From Baseline to Week 6 Compared to 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. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous. | Baseline and 6 weeks | No |
Primary | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 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. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous. | Baseline and 24 weeks | No |
Secondary | DAS28 EULAR Response at Week 6 | Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous. | 6 weeks | No |
Secondary | DAS28 EULAR Response at Week 24 | Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous. | 24 weeks | No |
Secondary | Proportion of Patients Achieving ACR20 up to Week 24 | 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. | 6 and 24 weeks | No |
Secondary | Proportion of Patients Achieving ACR50 up to Week 24 | 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. | 6 and 24 weeks | No |
Secondary | Proportion of Patients Achieving ACR70 up to Week 24 | 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. | 6 and 24 weeks | No |
Secondary | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | 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 CRP) or the physician and patient's own asessment 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 6. Treatment difference: difference between fostamatinib and placebo groups. | Baseline and 6 weeks | No |
Secondary | ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | 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 CRP) or the physician and patient's own asessment 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. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 24. Treatment difference: difference between fostamatinib and adalimumab groups. | Baseline and 24 weeks | No |
Secondary | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category 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 a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. | Baseline and 6 weeks | No |
Secondary | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category 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 a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. | Baseline and 24 weeks | No |
Secondary | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous. | Baseline and 24 weeks | No |
Secondary | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous. | Baseline and 24 weeks | No |
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