A Study to Evaluate the Efficacy and Safety of Mabthera Alone and in Combination With Either Cyclophosphamide or Methotrexate in Patients With Rheumatoid Arthritis

Roche

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Cyclophosphamide; Other: Placebo Cyclophosphamide; Other: Placebo Rituximab; Drug: Methotrexate; Drug: Rituximab; Other: Placebo Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT02693210

WA16291

Details and patient eligibility

About

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.

Enrollment: 161 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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161 participants in 4 patient groups

Group A: Methotrexate

Active Comparator group

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.

Treatment:

Other: Placebo Cyclophosphamide

Other: Placebo Rituximab

Drug: Methotrexate

Group B: Rituximab Monotherapy

Experimental group

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.

Treatment:

Other: Placebo Cyclophosphamide

Drug: Rituximab

Other: Placebo Methotrexate

Group C: Rituximab and Cyclophosphamide

Experimental group

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.

Treatment:

Drug: Cyclophosphamide

Drug: Rituximab

Other: Placebo Methotrexate

Group D: Methotrexate and Rituximab

Experimental group

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.

Treatment:

Other: Placebo Cyclophosphamide

Drug: Methotrexate

Drug: Rituximab