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.

Rheumatoid Arthritis Clinical Trial

— OSKIRA - 2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01197534
• Other study ID #: D4300C00002
• Secondary ID: 2010-020744-35
• Status: Completed
• Phase: Phase 3
• First received: September 8, 2010
• Last updated: March 13, 2014
• Start date: September 2010
• Est. completion date: March 2013

Study information

• Verified date: March 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesIndia: Drugs Controller General of IndiaIsrael: Ministry of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencySerbia and Montenegro: Agency for Drugs and Medicinal DevicesSouth Africa: Medicines Control CouncilSpain: Agencia Española de Medicamentos y Productos SanitariosUkraine: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• 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 disease modifying anti-rheumatic drug (DMARD) 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: 913
• Est. completion date: March 2013
• Est. primary completion date: March 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

• 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

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
Canada	Research Site	Bowmanville	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Reading
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-rivieres	Quebec
Canada	Research Site	Winnipeg	Manitoba
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Bruntal
Czech Republic	Research Site	Ceska Lipa
Czech Republic	Research Site	Ceske Budejovice
Czech Republic	Research Site	Hlucin
Czech Republic	Research Site	Liberec
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	Sokolov
Czech Republic	Research Site	Terezin
Czech Republic	Research Site	Zlin
Germany	Research Site	Erlangen
Germany	Research Site	Hamburg
Germany	Research Site	Muenchen
India	Research Site	Ahmedabad	Gujarat
India	Research Site	Bangalore	Karnataka
India	Research Site	Coimbatore	Tamil Nadu
India	Research Site	Gandhinagar	Gujarat
India	Research Site	Hyderabad	Andhra Pradesh
India	Research Site	Lucknow
India	Research Site	Madurai	Tamil Nadu
India	Research Site	Mangalore	Karnataka
India	Research Site	Mumbai	Maharashtra
India	Research Site	Pune	Maharashtra
India	Research Site	Vadodara	Gujarat
Israel	Research Site	Ashkelon
Israel	Research Site	Beer Yaakov
Israel	Research Site	Haifa
Israel	Research Site	Kfar-saba
Israel	Research Site	Petah-tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Ramat-gan
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Italy	Research Site	Jesi	AN
Italy	Research Site	Legnano	MI
Italy	Research Site	Udine	UD
Italy	Research Site	Varese	VA
Latvia	Research Site	Liepaja
Latvia	Research Site	Riga
Latvia	Research Site	Valmiera
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Klaipeda
Lithuania	Research Site	Siauliai
Portugal	Research Site	Aveiro
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Romania	Research Site	Baia Mare
Romania	Research Site	Brailari
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Ploiesti
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Serbia	Research Site	Niska Banja
Serbia	Research Site	Novi Sad
South Africa	Research Site	Cape Town	W Cape
South Africa	Research Site	Durban	Kz-natal
South Africa	Research Site	Kempron Park	Gauteng
South Africa	Research Site	Port Elizabeth
South Africa	Research Site	Pretoria	Gauteng
South Africa	Research Site	Stellenbosch
Spain	Research Site	Barcelona
Spain	Research Site	Getafe
Spain	Research Site	La Laguna (tenerife)	Canarias
Spain	Research Site	Merida	Extremadura
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Simferopol
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporyzhzhya
United Kingdom	Research Site	Basingstoke
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Eastbourne	Sussex
United Kingdom	Research Site	London
United Kingdom	Research Site	Maidstone	Kent
United Kingdom	Research Site	Newcastle Upon Tyne
United Kingdom	Research Site	Solihull	West Midlands
United Kingdom	Research Site	Stoke on Trent
United Kingdom	Research Site	Swindon
United States	Research Site	Amarillo	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boise	Idaho
United States	Research Site	Brandon	Florida
United States	Research Site	Brooklyn	New York
United States	Research Site	Canton	Georgia
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chesapeake	Virginia
United States	Research Site	Crofton	Maryland
United States	Research Site	Cumberland	Maryland
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Decatur	Georgia
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Durham	North Carolina
United States	Research Site	Elizabethtown	Kentucky
United States	Research Site	Flowood	Mississippi
United States	Research Site	Glendale	Arizona
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hagerstown	Maryland
United States	Research Site	Hot Springs	Arkansas
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Kalispell	Montana
United States	Research Site	Las Cruces	New Mexico
United States	Research Site	Lubbock	Texas
United States	Research Site	Macon	Georgia
United States	Research Site	Manalapan	New Jersey
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	Omaha	Nebraska
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
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	Scottsdale	Arizona
United States	Research Site	South Bend	Indiana
United States	Research Site	St. Louis	Missouri
United States	Research Site	Syracuse	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	Tucson	Arizona
United States	Research Site	Venice	Florida
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Reading	Pennsylvania
United States	Research Site	Zephyr Hills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Czech Republic,  Germany,  India,  Israel,  Italy,  Latvia,  Lithuania,  Portugal,  Romania,  Serbia,  South Africa,  Spain,  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. 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 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. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day.	1 week	No
Secondary	Proportion of Patients Achieving ACR50, Comparison Between Fostamatinib and Placebo at 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. 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, Comparison Between Fostamatinib and Placebo at 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. 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. Mean refers to change at Week 24.	Baseline and 24 weeks	No
Secondary	Proportion of Patients Achieving DAS28-CRP <2.6 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. 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, 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. 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 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. 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.	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 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.	Baseline and 24 weeks	No
Secondary	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 were excluded from the analysis. ANCOVA = analysis of covariance, BID = twice daily, IP = investigational product, 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 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.	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 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.	Baseline and 24 weeks	No

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