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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02693210
• Other study ID #: WA16291
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2016
• Last updated: October 29, 2016
• Start date: February 2001
• Est. completion date: August 2004

Study information

• Verified date: October 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Centralna Ewidencja Bada 324 Klinicznych
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: August 2004
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Cyclophosphamide
Participants will receive 750 mg infusions of cyclophosphamide on Days 3 and 17
• Methotrexate
Participants will receive >= 10 mg/week methotrexate orally up to 24 weeks

Other:
• Placebo Cyclophosphamide
Participants will receive placebo in place of cyclophosphamide on Days 3 and 17
• Placebo Methotrexate
Participants will receive weekly oral placebo in place of Methotrexate
• Placebo Rituximab
Participants will receive placebo in place of rituximab on days 1 and 15

Drug:
• Rituximab
Participants will receive 1g infusions of rituximab on Days 1 and 15

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Czech Republic,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants achieving American College of Rheumatology (ACR) 50 response at Week 24		Week 24	No
Secondary	Percentage of participants achieving ACR 20 and ACR 70 responses at Week 24		Week 24	No
Secondary	Area Under the Curve (AUC) of American College of Rheumatology Response (ACRn)		Baseline up to Week 24	No
Secondary	AUC of the mean Disease Activity Scores (DAS)		Baseline up to Week 24	No
Secondary	Change from Baseline in the Swollen Joint Count		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	Change from Baseline in the Tender Joint Count		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	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	No
Secondary	Change from Baseline in physician's global assessment of disease activity using VAS		Baseline, Weeks 8, 12, 16, 20 and 24	No
Secondary	Change from Baseline in the Health Assessment Questionnaire - Disease Index (HAQ-DI) scores		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	Change from Baseline in participant's pain measured by VAS		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	Change from Baseline in C-Reactive Protein (CRP) Levels		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	Change from Baseline in Erythrocyte Sedimentation Rate (ESR)		Baseline, Weeks 12, 16, 20 and 24	No
Secondary	Mean change in Rheumatoid factor levels at 24 weeks		Baseline and Week 24	No
Secondary	Percentage of participants who withdrew due to insufficient therapeutic response		Up to 24 Weeks	No