Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Disease Modifying Anti-rheumatic Drug (DMARD) But Not Responding. (OSKIRA - 2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01197534
First received: September 8, 2010
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The purpose of the study is to evaluate the effectiveness of two dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking disease modifying anti-rheumatic drug (DMARD) but not responding. The study will last for 1 year.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: fostamatinib
Drug: placebo, fostamatinib
Phase 3

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-2): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With an Inadequate Response to DMARDs

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo [ Time Frame: 24 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.


Secondary Outcome Measures:
  • Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1 [ 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.

  • Proportion of Patients Achieving ACR50, Comparison Between Fostamatinib and Placebo at Week 24 [ Time Frame: 24 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.

  • Proportion of Patients Achieving ACR70, Comparison Between Fostamatinib and Placebo at Week 24 [ Time Frame: 24 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 CRP) and the physician and patient's own assessments of disease activity, pain and physical function. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.

  • ACRn - Comparison Between Fostamatinib and Placebo at Week 24 [ Time Frame: Baseline and 24 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 CRP) 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. BID = twice daily, CI = confidence interval, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. Mean refers to change at Week 24.

  • Proportion of Patients Achieving DAS28-CRP <2.6 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. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

  • Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and Placebo [ Time Frame: 24 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. A DAS28-CRP score of <2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR=odds ratio, PO = orally, QD=once a day.

  • Proportion of Patients Achieving DAS28 EULAR Response at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. 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.

  • HAQ-DI Response - Comparison of the Change(>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then 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. The HAQ-DI response is a reduction from baseline in HAQ-DI score 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.

  • Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result were excluded from the analysis. ANCOVA = analysis of covariance, BID = twice daily, IP = investigational product, QD = once a day.

  • SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    SF-36: 36-item Short Form Health Survey, 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 0-100. 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+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.

  • SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24 [ Time Frame: Baseline and 24 weeks ] [ Designated as safety issue: No ]
    SF-36: 36-item Short Form Health Survey, 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 0-100. 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+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.


Enrollment: 913
Study Start Date: September 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dosing Regimen A
Oral Treatment
Drug: fostamatinib
fostamatinib 100 mg twice daily
Experimental: Dosing Regimen B
Oral Treatment
Drug: fostamatinib
fostamatinib 100 mg twice daily/ 150 mg once daily
Placebo Comparator: Dosing Regimen C
Oral Treatment
Drug: placebo, fostamatinib
Placebo for 24 weeks followed by fostamatinib 100 mg twice daily.

Detailed Description:

Sub-study:

Full title: Optional Genetic Research

Date: 18 June 2010

Version: 1

Objectives: To collect and store, with appropriate consent ,DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or methotrexate; and/or susceptibility to, progression of and prognosis of RA

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Active rheumatoid arthritis (RA) diagnosed after the age of 16
  • Treatment with one the following disease modifying anti-rheumatic drug: methotrexate, sulfasalazine, hydroxychloroquine or chloroquine
  • 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 one of the following: documented history of positive rheumatoid factor (blood test), current presence of 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
  • Previous failure to respond to a TNF alpha antagonist, anakinra or previous treatment with other biological agent
  • Severe renal impairment
  • Neutropenia
  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: NCT01197534

  Show 154 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Neil MacKillop, MD PhD AstraZeneca
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01197534     History of Changes
Other Study ID Numbers: D4300C00002, 2010-020744-35
Study First Received: September 8, 2010
Results First Received: November 22, 2013
Last Updated: March 13, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
India: Drugs Controller General of India
Israel: Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014