Back to resultsA Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cyclophosphamide
Methotrexate
Placebo Cyclophosphamide
Placebo Methotrexate
Placebo Rituximab
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Arm Label
Group A: Methotrexate
Group B: Rituximab Monotherapy
Group C: Rituximab and Cyclophosphamide
Group D: Methotrexate and Rituximab
Arm Description
Participants 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.
Participants 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.
Participants 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.
Participants 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.
Outcomes
Primary Outcome Measures
Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
Secondary Outcome Measures
Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24
Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)
AUC of the mean Disease Activity Scores (DAS)
Change from Baseline in the Swollen Joint Count
Change from Baseline in the Tender Joint Count
Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS)
Change from Baseline in physician's global assessment of disease activity using VAS
Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores
Change from Baseline in participant's pain measured by VAS
Change from Baseline in C-Reactive Protein (CRP) Levels
Change from Baseline in Erythrocyte Sedimentation Rate (ESR)
Mean change in Rheumatoid factor levels at 24 weeks
Percentage of participants who withdrew due to insufficient therapeutic response
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02693210
Brief Title
A Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
February 2001 (undefined)
Primary Completion Date
August 2002 (Actual)
Study Completion Date
August 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
161 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: Methotrexate
Arm Type
Active Comparator
Arm Description
Participants 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.
Arm Title
Group B: Rituximab Monotherapy
Arm Type
Experimental
Arm Description
Participants 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.
Arm Title
Group C: Rituximab and Cyclophosphamide
Arm Type
Experimental
Arm Description
Participants 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.
Arm Title
Group D: Methotrexate and Rituximab
Arm Type
Experimental
Arm Description
Participants 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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Participants will receive >= 10 mg/week methotrexate orally up to 24 weeks
Intervention Type
Other
Intervention Name(s)
Placebo Cyclophosphamide
Intervention Description
Participants will receive placebo in place of cyclophosphamide on Days 3 and 17
Intervention Type
Other
Intervention Name(s)
Placebo Methotrexate
Intervention Description
Participants will receive weekly oral placebo in place of Methotrexate
Intervention Type
Other
Intervention Name(s)
Placebo Rituximab
Intervention Description
Participants will receive placebo in place of rituximab on days 1 and 15
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Participants will receive 1g infusions of rituximab on Days 1 and 15
Primary Outcome Measure Information:
Title
Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24
Time Frame
Week 24
Title
Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)
Time Frame
Baseline up to Week 24
Title
AUC of the mean Disease Activity Scores (DAS)
Time Frame
Baseline up to Week 24
Title
Change from Baseline in the Swollen Joint Count
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Change from Baseline in the Tender Joint Count
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS)
Time Frame
Baseline, Weeks 8, 12, 16, 20 and 24
Title
Change from Baseline in physician's global assessment of disease activity using VAS
Time Frame
Baseline, Weeks 8, 12, 16, 20 and 24
Title
Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Change from Baseline in participant's pain measured by VAS
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Change from Baseline in C-Reactive Protein (CRP) Levels
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Change from Baseline in Erythrocyte Sedimentation Rate (ESR)
Time Frame
Baseline, Weeks 12, 16, 20 and 24
Title
Mean change in Rheumatoid factor levels at 24 weeks
Time Frame
Baseline and Week 24
Title
Percentage of participants who withdrew due to insufficient therapeutic response
Time Frame
Up to 24 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hofffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
City
Kogarah
ZIP/Postal Code
2217
Country
Australia
City
Woodville
ZIP/Postal Code
5011
Country
Australia
City
Diepenbeek
ZIP/Postal Code
3590
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1M4
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X5
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 1S6
Country
Canada
City
Praha
ZIP/Postal Code
128 50
Country
Czech Republic
City
Leipzig
ZIP/Postal Code
04107
Country
Germany
City
Ratingen
ZIP/Postal Code
40882
Country
Germany
City
Wiesbaden
ZIP/Postal Code
65191
Country
Germany
City
Haifa
ZIP/Postal Code
31048
Country
Israel
City
Haifa
ZIP/Postal Code
34354
Country
Israel
City
Brescia
ZIP/Postal Code
25123
Country
Italy
City
Genova
ZIP/Postal Code
16132
Country
Italy
City
Modena
ZIP/Postal Code
41100
Country
Italy
City
Siena
ZIP/Postal Code
53100
Country
Italy
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
City
Lublin
ZIP/Postal Code
20-022
Country
Poland
City
Poznan
ZIP/Postal Code
61-545
Country
Poland
City
Warszawa
ZIP/Postal Code
02-637
Country
Poland
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
City
Guadalajara
ZIP/Postal Code
19002
Country
Spain
City
La Laguna
ZIP/Postal Code
38320
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
City
Cannock
ZIP/Postal Code
WS11 5XY
Country
United Kingdom
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
City
London
ZIP/Postal Code
W1P 9PG
Country
United Kingdom
City
Stoke-on-trent
ZIP/Postal Code
ST6 7AG
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis
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