Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Not Responding.

Rheumatoid Arthritis Clinical Trial

— OSKIRA - 1  

Official title:

(OSKIRA-1): 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 Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197521
• Other study ID #: D4300C00001
• Secondary ID: 2010-020743-12
• Status: Completed
• Phase: Phase 3
• First received: September 8, 2010
• Last updated: February 27, 2014
• Start date: September 2010
• Est. completion date: November 2012

Study information

• Verified date: February 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyEstonia: The State Agency of MedicineFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Hungary: National Institute of PharmacyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug ControlSpain: Agencia Española de Medicamentos y Productos SanitariosUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyAustralia: Department of Health and Ageing Therapeutic Goods AdministrationIndia: Drugs Controller General of IndiaArgentina: National Administration of Drugs, Food & Medical Technology (ANMAT)Brazil: National Health Surveillance AgencyChile: Instituto de Salud Pública de ChileMexico: Federal Commission for Sanitary Risks ProtectionPeru: General Directorate of Pharmaceuticals, Devices, and Drugs
• 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 but not responding. The study will last for 1 year.

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: 923
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• 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 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

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, fostamatinib
Placebo for 24 weeks followed by fostamatinib 100 mg twice daily

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autonoma Bs As	CBA
Argentina	Research Site	Cordoba	CRD
Argentina	Research Site	Quilmes
Argentina	Research Site	Reading	Berkshire
Argentina	Research Site	Rosario	Santa Fe
Argentina	Research Site	San Juan
Argentina	Research Site	San Miguel de Tucuman	TUC
Australia	Research Site	Cairns	Queensland
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Southport	Queensland
Belgium	Research Site	Brussels
Belgium	Research Site	Yvoir
Brazil	Research Site	Curitiba	PR
Brazil	Research Site	Recife	PE
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo	SP
Brazil	Research Site	Vitoria	ES
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sevlievo
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Veliko Tarnovo
Chile	Research Site	Osorno	X Region
Chile	Research Site	Santiago
Estonia	Research Site	Parnu
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Orleans Cedex 1
France	Research Site	Paris Cedex 13
Hungary	Research Site	Balatonfured
Hungary	Research Site	Bekescsaba
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Mako
Hungary	Research Site	Sopron
Hungary	Research Site	Szentes
Hungary	Research Site	Zalaegerszeg-pozva
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Bangalore	Karnataka
India	Research Site	Calcutta
India	Research Site	Hyderabad
India	Research Site	Lucknow	Uttar Pradesh
India	Research Site	Mangalore	Karnataka
India	Research Site	Nagpur	Maharshtra
India	Research Site	Secunderabad	Andhra Pradesh
India	Research Site	Udupi	Karnataka
India	Research Site	Vishakhapatnam	Andhra Pradesh
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara	JAL
Mexico	Research Site	Mexicali
Mexico	Research Site	Mexico	Distrito Federal
Mexico	Research Site	Monterrey	Nuevo Leon
Mexico	Research Site	Obrergon	SON
Mexico	Research Site	Saltillo	Coahuila
Mexico	Research Site	San Luis Potosi
Peru	Research Site	Arequipa
Peru	Research Site	Lima
Peru	Research Site	Pueblo Libre	Lima
Poland	Research Site	Bytom
Poland	Research Site	Chelm Slaski
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Zyrardow
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Poprad
Slovakia	Research Site	Rimavska Sobota
Slovakia	Research Site	Zilina
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Ivano-frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kiev
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odessa
Ukraine	Research Site	Vinnytsya
Ukraine	Research Site	Zaporyzhzhya
United Kingdom	Research Site	Christchurch
United Kingdom	Research Site	Ipswich
United Kingdom	Research Site	London
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	Albuquerque	New Mexico
United States	Research Site	Anniston	Alabama
United States	Research Site	Asheville	North Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Bridgeport	Connecticut
United States	Research Site	Brooklyn	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Dallas	Texas
United States	Research Site	Daytona Beach	Florida
United States	Research Site	Erie	Pennsylvania
United States	Research Site	Florissant	Missouri
United States	Research Site	Flowood	Mississippi
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Hixson	Tennessee
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntsville	Alabama
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	Kalispell	Montana
United States	Research Site	Lake Oswego	Oregon
United States	Research Site	Lewes	Delaware
United States	Research Site	Long Beach	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Memphis	Tennessee
United States	Research Site	Mesquite	Texas
United States	Research Site	Ocala	Florida
United States	Research Site	Olean	New York
United States	Research Site	Perrysburg	Ohio
United States	Research Site	Richmond Heights	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Maria	California
United States	Research Site	Santa Monica	California
United States	Research Site	Springfield	Illinois
United States	Research Site	St Louis	Missouri
United States	Research Site	Tucson	Arizona
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Waxford	Pennsylvania
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Chile,  Estonia,  France,  Hungary,  India,  Mexico,  Peru,  Poland,  Slovakia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With 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 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, PO=orally, QD=once a day.	24 weeks	No
Primary	Change From Baseline to Week 24 in mTSS, 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 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 have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, PO=orally, QD=once a day.	Baseline and 24 weeks	No
Secondary	ACR20 - Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1	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, PO=orally.	1 week	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, PO=orally, QD=once a day.	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, PO=orally, QD=once a day.	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 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, RA=rheumatoid arthritis. Mean refers to change at Week 24.	24 weeks	No
Secondary	Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12	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.	12 weeks	No
Secondary	Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24	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.	24 weeks	No
Secondary	Proportion of Patients Achieving DAS28-CRP 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, 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	HAQ-DI Response - Comparison of the Change (>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24	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: 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.	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, 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 Component Scores (PCS) 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. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease modifying antirheumatic drug, PO=orally, QD=once daily, QoL=quality of life.	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, 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. Mental Component Scores (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. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease modifying antirheumatic drug, PO=orally, QD=once daily, QoL=quality of life.	Baseline and 24 weeks	No