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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02093026




Registration number
NCT02093026
Ethics application status
Date submitted
19/03/2014
Date registered
20/03/2014
Date last updated
13/03/2017

Titles & IDs
Public title
Extension Study to Assess the Efficacy and Safety of Repeat Treatment With Rituximab (MabThera) in Participants With Active Rheumatoid Arthritis (RA)
Scientific title
An Open-label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera®/Rituxan®) in Patients With Active Rheumatoid Arthritis
Secondary ID [1] 0 0
U2653g
Secondary ID [2] 0 0
WA16855
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rituximab
Treatment: Drugs - Methotrexate
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Folic Acid

Experimental: Rituximab - Participants will receive rituximab 1 gram intravenously (IV) on Days 1 and 15 of each course of retreatment. In addition, participants will receive methotrexate 10-25 milligrams per week (mg/week) orally or parenterally, methylprednisolone 100 mg IV 30 minutes prior to both rituximab infusions, and a stable dose of folic acid greater than or equal to (>=) 5 mg/week or equivalent. Participants will receive retreatment (next course of rituximab repeat treatment) within 2 weeks of meeting the retreatment criteria as defined in the protocol (minimum of 24 weeks after the first [Day 1] infusion of the last course of rituximab). Repeat treatment will be based on the investigator's decision of prior clinical response to rituximab, clinical need and evidence of active disease (Disease Activity Score in 28 joints >=2.6). Retreatment with rituximab will be continued until withdrawal of consent or study treatment completion on 31 December 2011, whichever is sooner.


Treatment: Drugs: Rituximab
Participants will receive rituximab 1 gram IV on Days 1 and 15 of each course of retreatment.

Treatment: Drugs: Methotrexate
Participants will receive methotrexate 10-25 mg/week orally or parenterally.

Treatment: Drugs: Methylprednisolone
Participants will receive methylprednisolone 100 mg IV 30 minutes prior to each rituximab infusion.

Treatment: Drugs: Folic Acid
Participants will receive folic acid >= 5 mg/week or equivalent.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With an American College of Rheumatology 20 (ACR20) Response After First Course
Timepoint [1] 0 0
24 weeks after first course of rituximab (up to approximately 26 weeks)
Primary outcome [2] 0 0
Percentage of Participants With ACR20 Response After Second Course
Timepoint [2] 0 0
24 weeks after second course of rituximab (median duration of 90.9 weeks)
Primary outcome [3] 0 0
Percentage of Participants With ACR20 Response After Third Course
Timepoint [3] 0 0
24 weeks after third course of rituximab (median duration of 162.9 weeks)
Primary outcome [4] 0 0
Percentage of Participants With ACR20 Response After Fourth Course
Timepoint [4] 0 0
24 weeks after fourth course of rituximab (median duration of 232 weeks)
Primary outcome [5] 0 0
Percentage of Participants With ACR20 Response After Fifth Course
Timepoint [5] 0 0
24 weeks after fifth course of rituximab (median duration of 297.3 weeks)
Primary outcome [6] 0 0
Percentage of Participants With ACR20 Response After Sixth Course
Timepoint [6] 0 0
24 weeks after sixth course of rituximab (median duration of 354.4 weeks)
Primary outcome [7] 0 0
Percentage of Participants With ACR20 Response After Seventh Course
Timepoint [7] 0 0
24 weeks after seventh course of rituximab (median duration of 406.7 weeks)
Secondary outcome [1] 0 0
Percentage of Participants With ACR50 and ACR70 Response
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
American College of Rheumatology Index of Improvement (ACRn) Response
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Percentage of Participants With Low Disease Activity and Clinical Remission Based on DAS28-ESR
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Percentage of Participants With European League Against Rheumatism (EULAR) Response of 'Good' or 'Moderate'
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 24 Weeks Following Each Course
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Change From Baseline in Total Rheumatoid Factors (RF) at 24 Weeks Following Each Course
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Percentage of Participants Who Discontinued Treatment Due to Insufficient Response
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Time Since Last Treatment Course
Timepoint [8] 0 0
Baseline up to 10 years

Eligibility
Key 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
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2002
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2012
Sample size
Target
Accrual to date
Final
465
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
- Maroochydore
Recruitment hospital [2] 0 0
- Melbourne
Recruitment hospital [3] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
3168 - Melbourne
Recruitment postcode(s) [3] 0 0
6979 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Belgium
State/province [25] 0 0
Gent
Country [26] 0 0
Brazil
State/province [26] 0 0
PR
Country [27] 0 0
Brazil
State/province [27] 0 0
SP
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Newfoundland and Labrador
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Czech Republic
State/province [32] 0 0
Praha
Country [33] 0 0
Finland
State/province [33] 0 0
Heinola
Country [34] 0 0
Finland
State/province [34] 0 0
Helsinki
Country [35] 0 0
Germany
State/province [35] 0 0
Köln
Country [36] 0 0
Germany
State/province [36] 0 0
Leipzig
Country [37] 0 0
Germany
State/province [37] 0 0
Ratingen
Country [38] 0 0
Germany
State/province [38] 0 0
Regensburg
Country [39] 0 0
Germany
State/province [39] 0 0
Wuerzburg
Country [40] 0 0
Israel
State/province [40] 0 0
Haifa
Country [41] 0 0
Italy
State/province [41] 0 0
Emilia-Romagna
Country [42] 0 0
Italy
State/province [42] 0 0
Friuli-Venezia Giulia
Country [43] 0 0
Italy
State/province [43] 0 0
Liguria
Country [44] 0 0
Italy
State/province [44] 0 0
Lombardia
Country [45] 0 0
Mexico
State/province [45] 0 0
Mexico City
Country [46] 0 0
Mexico
State/province [46] 0 0
Mexico
Country [47] 0 0
Mexico
State/province [47] 0 0
Monterrey
Country [48] 0 0
New Zealand
State/province [48] 0 0
Auckland City
Country [49] 0 0
New Zealand
State/province [49] 0 0
Auckland
Country [50] 0 0
Poland
State/province [50] 0 0
Bialystok
Country [51] 0 0
Poland
State/province [51] 0 0
Lublin
Country [52] 0 0
Poland
State/province [52] 0 0
Poznan
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Spain
State/province [55] 0 0
Badajoz
Country [56] 0 0
Spain
State/province [56] 0 0
La Coruña
Country [57] 0 0
Spain
State/province [57] 0 0
Tenerife
Country [58] 0 0
Spain
State/province [58] 0 0
Madrid
Country [59] 0 0
Spain
State/province [59] 0 0
Sevilla
Country [60] 0 0
Sweden
State/province [60] 0 0
Göteborg
Country [61] 0 0
Sweden
State/province [61] 0 0
Stockholm
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Birmingham
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Cambridge
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Cannock
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leeds
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Stoke-on-trent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02093026
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries