Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate and Have Had Inadequate Response to Single TNF-alpha Antagonist

Rheumatoid Arthritis Clinical Trial

— OSKIRA - 3  

Official title:

(OSKIRA-3): 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 Inadequate Response to a TNF-alpha Antagonist

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197755
• Other study ID #: D4300C00003
• Secondary ID: 2010-020745-27
• Status: Completed
• Phase: Phase 3
• First received: September 8, 2010
• Last updated: February 27, 2014
• Start date: September 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: National Administration of Drugs, Food & Medical Technology (ANMAT)Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIsrael: Ministry of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionPortugal: National Pharmacy and Medicines InstituteSouth Africa: Medicines Control CouncilSpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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 methotrexate and have had an inadequate response to a single TNF-alpha antagonist. The study will last for approximately six months.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Active rheumatoid arthritis (RA) diagnosed after the age of 16

• Currently taking methotrexate

• 6 or more swollen joints and 6 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 12months 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 anakinra or previous treatment with biological agent (other than TNF alpha antagonists including rituximab, abatacept and tocilizumab)

• Severe renal impairment

• Neutropenia

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 100 mg twice daily
• fostamatinib
fostamatinib 100 mg twice daily/150 mg once daily
• placebo
Placebo twice daily

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires	Caba
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Cordoba	CRD
Argentina	Research Site	Quilmes
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario	Santa Fe
Argentina	Research Site	San Juan
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Miguel de Tucuman	TUC
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Belgium	Research Site	Liege
Belgium	Research Site	Yvoir
Brazil	Research Site	Curitiba	PR
Brazil	Research Site	Goiania	GO
Brazil	Research Site	Porto Alegre	Brasil
Brazil	Research Site	Sao Paulo	SP
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Pointe-claire	Quebec
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	St John's	Newfoundland and Labrador
Canada	Research Site	Toronto	Ontario
Czech Republic	Research Site	Bruntal
Czech Republic	Research Site	Ceske Budejovice
Czech Republic	Research Site	Hlucin
Czech Republic	Research Site	Ostrava-trebovice
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Zlin
France	Research Site	Orleans Cedex 1
Germany	Research Site	Aachen	Nordrhein Westfalen
Germany	Research Site	Erlangen
Germany	Research Site	Frankfurt
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg	HH
Germany	Research Site	Heidelberg
Germany	Research Site	Leipzig	SN
Germany	Research Site	Muenchen
Hungary	Research Site	Budapest
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Israel	Research Site	Kfar Saba
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel-hashomer
Italy	Research Site	Ferrara	FE
Italy	Research Site	Jesi	AN
Mexico	Research Site	Chihuahua
Mexico	Research Site	DF
Mexico	Research Site	Monterrey
Mexico	Research Site	Obrergon	SON
Mexico	Research Site	Saltillo
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
South Africa	Research Site	Cape Town
South Africa	Research Site	Pretoria
South Africa	Research Site	Stellenbosch
Spain	Research Site	Barcelona
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Christchurch
United Kingdom	Research Site	Eastbourne	Sussex
United Kingdom	Research Site	Ipswich
United Kingdom	Research Site	London
United Kingdom	Research Site	Maidstone	Kent
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Reading	Berkshire
United Kingdom	Research Site	Warrington	Cheshire
United Kingdom	Research Site	Westcliff-on-the Sea
United Kingdom	Research Site	Wirral
United States	Research Site	Albany	New York
United States	Research Site	Amarillo	Texas
United States	Research Site	Anniston	Alabama
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Brandon	Florida
United States	Research Site	Bridgeport	Connecticut
United States	Research Site	Brooklyn	New York
United States	Research Site	Canton	Georgia
United States	Research Site	Cedar Rapids	Iowa
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Crofton	Maryland
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Decatur	Illinois
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Durham	North Carolina
United States	Research Site	Elizabethtown	Kentucky
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Florissant	Missouri
United States	Research Site	Flowood	Mississippi
United States	Research Site	Glendale	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hixson	Tennessee
United States	Research Site	Hot Springs	Arkansas
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	Jacksonville	Florida
United States	Research Site	La Jolla	California
United States	Research Site	Lake Oswego	Oregon
United States	Research Site	Lansing	Michigan
United States	Research Site	Las Cruces	New Mexico
United States	Research Site	Lewes	Delaware
United States	Research Site	Long Beach	California
United States	Research Site	Mayfield Village	Ohio
United States	Research Site	Memphis	Tennessee
United States	Research Site	Mesa	Arizona
United States	Research Site	Nashville	Tennessee
United States	Research Site	Ocala	Florida
United States	Research Site	Olean	New York
United States	Research Site	Orlando	Florida
United States	Research Site	Palo Alto	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Richmond Heights	Missouri
United States	Research Site	Rochester	New York
United States	Research Site	Roslyn	New York
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Maria	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Smithtown	New York
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Torrance	California
United States	Research Site	Trumbull	Connecticut
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Tustin	California
United States	Research Site	Upland	California
United States	Research Site	Venice	Florida
United States	Research Site	West Reading	Pennsylvania
United States	Research Site	Worcester	Massachusetts
United States	Research Site	Zephyr Hills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Hungary,  Israel,  Italy,  Mexico,  Portugal,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Achieving ACR20 at Week 24, 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 daily.	24 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, QD = once daily.	1 week	No
Secondary	Proportion of Patients Achieving ACR50 at Week 24, 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 daily.	24 weeks	No
Secondary	Proportion of Patients Achieving ACR70 at Week 24, 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 daily.	24 weeks	No
Secondary	ACRn - Comparison Between Fostamatinib and Placebo 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 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 24. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.	Baseline and 24 weeks	No
Secondary	Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, 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 patients' 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 daily.	24 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 patients' own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. A 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 Achieving DAS28-CRP EULAR Response at Week 24, Comparison Between Fostamatinib and Placebo	Change from baseline in DAS28-CRP at Week 24 was categorised using the European League Against Rheumatism (EULAR) response criteria. BID = twice daily, CRP = C-reactive protein, 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.	24 weeks	No
Secondary	Proportion of Patients With a HAQ-DI Response at Week 24 - 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 the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygeine, 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. A 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.	24 weeks	No
Secondary	Change From Baseline to Week 24 in mTSS Score, Comparison Between Fostamatinib and Placebo	mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for eroisions and joint space narrowing and the results summed to give a value between 0 and 488. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values 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, PO = orally, QD = once a day.	Baseline and 24 weeks	No
Secondary	SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24	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 a mean of 50, standard deviation of 10. A higher score represents 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. Mean refers to change in scores at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once daily	Baseline and 24 weeks	No
Secondary	SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24	SF-36: 36 item short form health survey, as a measure of health-related quality of life. The SF-36 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 a mean of 50, standard deviation of 10. A higher score represents 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. Mean refers to change in score at Week 24. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once daily.	Baseline and 24 weeks	No

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