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

NCT ID: NCT02693210

Last Updated: 2016-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

161 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-02-28

Study Completion Date

2004-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Group A: Methotrexate

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.

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

Participants will receive \>= 10 mg/week methotrexate orally up to 24 weeks

Placebo Cyclophosphamide

Intervention Type OTHER

Participants will receive placebo in place of cyclophosphamide on Days 3 and 17

Placebo Rituximab

Intervention Type OTHER

Participants will receive placebo in place of rituximab on days 1 and 15

Group B: Rituximab Monotherapy

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.

Group Type EXPERIMENTAL

Placebo Cyclophosphamide

Intervention Type OTHER

Participants will receive placebo in place of cyclophosphamide on Days 3 and 17

Placebo Methotrexate

Intervention Type OTHER

Participants will receive weekly oral placebo in place of Methotrexate

Rituximab

Intervention Type DRUG

Participants will receive 1g infusions of rituximab on Days 1 and 15

Group C: Rituximab and Cyclophosphamide

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17

Placebo Methotrexate

Intervention Type OTHER

Participants will receive weekly oral placebo in place of Methotrexate

Rituximab

Intervention Type DRUG

Participants will receive 1g infusions of rituximab on Days 1 and 15

Group D: Methotrexate and Rituximab

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.

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

Participants will receive \>= 10 mg/week methotrexate orally up to 24 weeks

Placebo Cyclophosphamide

Intervention Type OTHER

Participants will receive placebo in place of cyclophosphamide on Days 3 and 17

Rituximab

Intervention Type DRUG

Participants will receive 1g infusions of rituximab on Days 1 and 15

Interventions

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Cyclophosphamide

Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17

Intervention Type DRUG

Methotrexate

Participants will receive \>= 10 mg/week methotrexate orally up to 24 weeks

Intervention Type DRUG

Placebo Cyclophosphamide

Participants will receive placebo in place of cyclophosphamide on Days 3 and 17

Intervention Type OTHER

Placebo Methotrexate

Participants will receive weekly oral placebo in place of Methotrexate

Intervention Type OTHER

Placebo Rituximab

Participants will receive placebo in place of rituximab on days 1 and 15

Intervention Type OTHER

Rituximab

Participants will receive 1g infusions of rituximab on Days 1 and 15

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hofffmann-La Roche

Locations

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Darlinghurst, , Australia

Site Status

Kogarah, , Australia

Site Status

Woodville, , Australia

Site Status

Diepenbeek, , Belgium

Site Status

Ghent, , Belgium

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Liège, , Belgium

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Winnipeg, Manitoba, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Prague, , Czechia

Site Status

Leipzig, , Germany

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Ratingen, , Germany

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Wiesbaden, , Germany

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Haifa, , Israel

Site Status

Haifa, , Israel

Site Status

Brescia, , Italy

Site Status

Genova, , Italy

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Modena, , Italy

Site Status

Siena, , Italy

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Leiden, , Netherlands

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Lublin, , Poland

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Poznan, , Poland

Site Status

Warsaw, , Poland

Site Status

Wroclaw, , Poland

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Guadalajara, , Spain

Site Status

Madrid, , Spain

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Madrid, , Spain

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San Cristóbal de La Laguna, , Spain

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Seville, , Spain

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Cannock, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Stoke-on-Trent, , United Kingdom

Site Status

Countries

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Australia Belgium Canada Czechia Germany Israel Italy Netherlands Poland Spain United Kingdom

Other Identifiers

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WA16291

Identifier Type: -

Identifier Source: org_study_id