Clinical trial NCT02693210: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-02-26
Enrollment: 161
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24
timeFrame: Week 24
measure: Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)
timeFrame: Baseline up to Week 24
measure: AUC of the mean Disease Activity Scores (DAS)
timeFrame: Baseline up to Week 24
measure: Change from Baseline in the Swollen Joint Count
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Change from Baseline in the Tender Joint Count
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Change from Baseline in participant's global assessment of disease activity using a Visual Analog Scale (VAS)
timeFrame: Baseline, Weeks 8, 12, 16, 20 and 24
measure: Change from Baseline in physician's global assessment of disease activity using VAS
timeFrame: Baseline, Weeks 8, 12, 16, 20 and 24
measure: Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Change from Baseline in participant's pain measured by VAS
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Change from Baseline in C-Reactive Protein (CRP) Levels
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Change from Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline, Weeks 12, 16, 20 and 24
measure: Mean change in Rheumatoid factor levels at 24 weeks
timeFrame: Baseline and Week 24
measure: Percentage of participants who withdrew due to insufficient therapeutic response
timeFrame: Up to 24 Weeks
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
city: Kogarah
country: Australia
city: Woodville
country: Australia
city: Diepenbeek
country: Belgium
city: Gent
country: Belgium
city: Liege
country: Belgium
city: Winnipeg
country: Canada
state: Manitoba
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Praha
country: Czech Republic
city: Leipzig
country: Germany
city: Ratingen
country: Germany
city: Wiesbaden
country: Germany
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Brescia
country: Italy
city: Genova
country: Italy
city: Modena
country: Italy
city: Siena
country: Italy
city: Leiden
country: Netherlands
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Guadalajara
country: Spain
city: La Laguna
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Cannock
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Stoke-on-trent
country: United Kingdom
Study officials:
affiliation: Hofffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: