Rheumatoid Arthritis
Conditions
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.
Interventions
DRUGCyclophosphamide
Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17
DRUGMethotrexate
Participants will receive \>= 10 mg/week methotrexate orally up to 24 weeks
OTHERPlacebo Cyclophosphamide
Participants will receive placebo in place of cyclophosphamide on Days 3 and 17
OTHERPlacebo Methotrexate
Participants will receive weekly oral placebo in place of Methotrexate
OTHERPlacebo Rituximab
Participants will receive placebo in place of rituximab on days 1 and 15
DRUGRituximab
Participants will receive 1g infusions of rituximab on Days 1 and 15
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24 | Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS) | Baseline, Weeks 8, 12, 16, 20 and 24 |
| Change from Baseline in physician's global assessment of disease activity using VAS | Baseline, Weeks 8, 12, 16, 20 and 24 |
| Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24 | Week 24 |
| Change from Baseline in participant's pain measured by VAS | Baseline, Weeks 12, 16, 20 and 24 |
| Change from Baseline in C-Reactive Protein (CRP) Levels | Baseline, Weeks 12, 16, 20 and 24 |
| Change from Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline, Weeks 12, 16, 20 and 24 |
| Mean change in Rheumatoid factor levels at 24 weeks | Baseline and Week 24 |
| Percentage of participants who withdrew due to insufficient therapeutic response | Up to 24 Weeks |
| Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores | Baseline, Weeks 12, 16, 20 and 24 |
Countries
Australia, Belgium, Canada, Czechia, Germany, Israel, Italy, Netherlands, Poland, Spain, United Kingdom
Outcome results
None listed