A Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis
A Randomised, Double Dummy Controlled, Parallel Group Study of the Efficacy and Safety of MabThera (Rituximab) Alone or in Combination With Either Cyclophosphamide or Methotrexate, in Patients With Rheumatoid Arthritis
1 other identifier
interventional
161
11 countries
33
Brief Summary
WA16291 is a Phase IIa "proof-of-concept" study. The primary objective of this study is to determine the safety and efficacy of rituximab (a B cell depleting chimeric monoclonal antibody) used either as monotherapy or in combination with methotrexate or cyclophosphamide in participants with rheumatoid arthritis who have failed prior Disease Modifying Anti-Rheumatic Drug (DMARD) therapy and currently have an inadequate clinical response to methotrexate.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 rheumatoid-arthritis
Started Feb 2001
Longer than P75 for phase_2 rheumatoid-arthritis
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2001
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2002
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2004
CompletedFirst Submitted
Initial submission to the registry
February 23, 2016
CompletedFirst Posted
Study publicly available on registry
February 26, 2016
CompletedNovember 1, 2016
October 1, 2016
1.5 years
February 23, 2016
October 29, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
Week 24
Secondary Outcomes (13)
Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24
Week 24
Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)
Baseline up to Week 24
AUC of the mean Disease Activity Scores (DAS)
Baseline up to Week 24
Change from Baseline in the Swollen Joint Count
Baseline, Weeks 12, 16, 20 and 24
Change from Baseline in the Tender Joint Count
Baseline, Weeks 12, 16, 20 and 24
- +8 more secondary outcomes
Study Arms (4)
Group A: Methotrexate
ACTIVE COMPARATORParticipants will receive methotrexate at dosage \>=10 milligrams per week (mg/week) orally as determined by the investigator. They also receive placebo infusion on days 1 and 15 in place of rituximab and on Days 3 and 17 in place of cyclophosphamide.
Group B: Rituximab Monotherapy
EXPERIMENTALParticipants will receive 1 g intravenous infusions of rituximab on Days 1 and 15. They also receive Weekly placebo orally instead of methotrexate and placebo infusion in place of cyclophosphamide on Days 3 and 17.
Group C: Rituximab and Cyclophosphamide
EXPERIMENTALParticipants will receive 1g IV infusion of rituximab on Days 1 and 15 and 750 mg infusion of Cyclophosphamide on Days 3 and 17. They also receive weekly oral placebo in place of methotrexate.
Group D: Methotrexate and Rituximab
EXPERIMENTALParticipants will receive \>=10 mg/week methotrexate orally along with 2 times 1 gram (g) rituximab IV infusions on Days 1 and 15. Participants will also receive placebo infusions on Days 3 and 17 in place of cyclophosphamide.
Interventions
Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17
Participants will receive \>= 10 mg/week methotrexate orally up to 24 weeks
Participants will receive placebo in place of cyclophosphamide on Days 3 and 17
Participants will receive weekly oral placebo in place of Methotrexate
Participants will receive placebo in place of rituximab on days 1 and 15
Participants will receive 1g infusions of rituximab on Days 1 and 15
Eligibility Criteria
You may qualify if:
- Participants with moderate to severe rheumatoid arthritis (RA) who have previously failed 1-5 DMARDS who currently have partial clinical response to treatment with methotrexate
- Using methotrexate as a single DMARD for at least 16 weeks, of which the last 4 weeks prior to baseline on a stable oral dose greater than or equal to (\>=) 10 milligrams per week (mg/week)
- \>=21 years of age
- Swollen Joint Count (SJC) and Tender Joint Count (TJC) \>= 8 (out of 66 and 68 joints respectively)
- At least 2 of the following parameters at Baseline: C- Reactive Protein \>= 15 mg/dL; Erythrocyte Sedimentation Rate \>= 30 millimeters per hour (mm/hr); Morning stiffness \>45 minutes
- Rheumatoid factor titer \>=20 International units per milliliter (IU/mL)
- Corticosteroid (less than or equal to \[=\<\] 12.5 milligrams per deciliter \[mg/d\] prednisone or equivalent) or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are permitted if stable for at least 4 weeks prior to baseline
You may not qualify if:
- American Rheumatism Association (ARA) Class IV RA disease
- Concurrent treatment with any DMARD (apart from randomized treatment) or anti-TNF-alpha therapy
- Active infection or history of recurrent significant infection
- Prior history of cancer including solid tumors and hematologic malignancies (except basal carcinoma of the skin that have been excised and cured)
- Evidence of serious uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders
- Bone/joint surgery within 6 weeks prior to screening
- Rheumatic Autoimmune disease other than RA
- Active rheumatoid vasculitis
- Prior history of gout
- Chronic fatigue syndrome
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
Unknown Facility
Darlinghurst, 2010, Australia
Unknown Facility
Kogarah, 2217, Australia
Unknown Facility
Woodville, 5011, Australia
Unknown Facility
Diepenbeek, 3590, Belgium
Unknown Facility
Ghent, 9000, Belgium
Unknown Facility
Liège, 4000, Belgium
Unknown Facility
Winnipeg, Manitoba, R3A 1M4, Canada
Unknown Facility
Toronto, Ontario, M5G 1X5, Canada
Unknown Facility
Montreal, Quebec, H2L 1S6, Canada
Unknown Facility
Prague, 128 50, Czechia
Unknown Facility
Leipzig, 04107, Germany
Unknown Facility
Ratingen, 40882, Germany
Unknown Facility
Wiesbaden, 65191, Germany
Unknown Facility
Haifa, 31048, Israel
Unknown Facility
Haifa, 34354, Israel
Unknown Facility
Brescia, 25123, Italy
Unknown Facility
Genova, 16132, Italy
Unknown Facility
Modena, 41100, Italy
Unknown Facility
Siena, 53100, Italy
Unknown Facility
Leiden, 2333 ZA, Netherlands
Unknown Facility
Lublin, 20-022, Poland
Unknown Facility
Poznan, 61-545, Poland
Unknown Facility
Warsaw, 02-637, Poland
Unknown Facility
Wroclaw, 50-556, Poland
Unknown Facility
Guadalajara, 19002, Spain
Unknown Facility
Madrid, 28007, Spain
Unknown Facility
Madrid, 28046, Spain
Unknown Facility
San Cristóbal de La Laguna, 38320, Spain
Unknown Facility
Seville, 41014, Spain
Unknown Facility
Cannock, WS11 5XY, United Kingdom
Unknown Facility
Leeds, LS1 3EX, United Kingdom
Unknown Facility
London, W1P 9PG, United Kingdom
Unknown Facility
Stoke-on-Trent, ST6 7AG, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hofffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 23, 2016
First Posted
February 26, 2016
Study Start
February 1, 2001
Primary Completion
August 1, 2002
Study Completion
August 1, 2004
Last Updated
November 1, 2016
Record last verified: 2016-10