Clinical trial NCT02093026: Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
Official title: An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2014-03-20
Enrollment: 465
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the long-term safety and efficacy of repeat treatment courses of rituximab, in combination with methotrexate in a disease-modifying anti-rheumatic drug (DMARD) inadequate responder population of participants who were previously randomized into studies WA16291 (NCT02693210) or WA17043/U2644g (NCT00074438). The study permits multiple re-treatments until the protocol-defined end-of-treatment date (31 December 2011). Participants will then enter a safety follow-up (SFU) period of at least 48 weeks. This will provide at least 7 years follow-up data on all participants initially randomized into WA16291 or WA17043/U2644g. Approximately 600 participants will potentially be eligible to enter this open label extension study from their respective feeder studies.


Eligibility criteria: Inclusion Criteria:

* participants with active RA
* completed 24 weeks of treatment in WA16291 or WA17043
* eligible for re-treatment, based on clinical symptoms (Disease Activity Score in 28 joints \>=2.6)
* females of childbearing potential using reliable contraception

Exclusion Criteria:

* participants who participated in rituximab studies WA16291 or WA17043 but withdrew into the safety follow-up phases of these trials
* previous rituximab non-responders
* current treatment with any other disease-modifying drug (apart from methotrexate), or any anti-tumor necrosis factor alfa, anti-interleukin-1, or other biologic therapies
* participants with known active infection of any kind
* evidence of any new or uncontrolled concomitant disease or development of any new contraindications which would preclude repeat treatment with rituximab
* history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* female participants who are pregnant or breastfeeding

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
timeFrame: 24 weeks after first course of rituximab (up to approximately 26 weeks)
measure: Percentage of Participants With ACR20 Response After Second Course
timeFrame: 24 weeks after second course of rituximab (median duration of 90.9 weeks)
measure: Percentage of Participants With ACR20 Response After Third Course
timeFrame: 24 weeks after third course of rituximab (median duration of 162.9 weeks)
measure: Percentage of Participants With ACR20 Response After Fourth Course
timeFrame: 24 weeks after fourth course of rituximab (median duration of 232 weeks)
measure: Percentage of Participants With ACR20 Response After Fifth Course
timeFrame: 24 weeks after fifth course of rituximab (median duration of 297.3 weeks)
measure: Percentage of Participants With ACR20 Response After Sixth Course
timeFrame: 24 weeks after sixth course of rituximab (median duration of 354.4 weeks)
measure: Percentage of Participants With ACR20 Response After Seventh Course
timeFrame: 24 weeks after seventh course of rituximab (median duration of 406.7 weeks)
Secondary outcomes:
measure: Percentage of Participants With ACR50 and ACR70 Response
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: American College of Rheumatology Index of Improvement (ACRn) Response
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
timeFrame: 24 weeks after first, second, third, fourth, fifth, sixth, and seventh course of rituximab (median duration of 26, 90.9, 162.9, 232, 297.3, 354.4, and 406.7 weeks, respectively)
measure: Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
timeFrame: First, second, third, fourth, fifth, sixth, and seventh course of rituximab (up to a median of approximately 2, 62, 124, 186, 248, 310, and 372 weeks, respectively)
measure: Time Since Last Treatment Course
timeFrame: Baseline up to 10 years
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: San Diego
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Aventura
country: United States
state: Florida
city: Boca Raton
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: South Miami
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state: Florida
city: Boise
country: United States
state: Idaho
city: Chicago
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state: Illinois
city: Chicago
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state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
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state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Lebanon
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state: New Hampshire
city: Voorhees
country: United States
state: New Jersey
city: Great Neck
country: United States
state: New York
city: Plainview
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Greenville
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Beachwood
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Mayfield
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: Dallas
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state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
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state: Washington
city: Glendale
country: United States
state: Wisconsin
city: Wausau
country: United States
state: Wisconsin
city: Maroochydore
country: Australia
state: Queensland
city: Melbourne
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Gent
country: Belgium
city: Curtiba
country: Brazil
state: PR
city: Campinas
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: St John's
country: Canada
state: Newfoundland and Labrador
city: London
country: Canada
state: Ontario
city: Praha
country: Czech Republic
city: Heinola
country: Finland
city: Helsinki
country: Finland
city: Köln
country: Germany
city: Leipzig
country: Germany
city: Ratingen
country: Germany
city: Regensburg
country: Germany
city: Wuerzburg
country: Germany
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Modena
country: Italy
state: Emilia-Romagna
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Mexico City
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: Auckland City
country: New Zealand
city: Auckland
country: New Zealand
city: Bialystok
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Merida
country: Spain
state: Badajoz
city: Santiago de Compostela
country: Spain
state: La Coruña
city: La Laguna
country: Spain
state: Tenerife
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Göteborg
country: Sweden
city: Stockholm
country: Sweden
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cannock
country: United Kingdom
city: Leeds
country: United Kingdom
city: Stoke-on-trent
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_CHAIR
References: