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A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate

Information source: Hoffmann-La Roche
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Rheumatoid Arthritis

Intervention: Rituximab (Biological); Placebo (Drug); Methylprednisolone (Drug); Methotrexate (Drug); Folic acid or folate (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Hoffmann-La Roche

Official(s) and/or principal investigator(s):
Clinical Trials, Study Director, Affiliation: Hoffmann-La Roche

Summary

This 3 arm study assessed the efficacy of rituximab (MabThera®/Rituxan®) in the prevention of progression of structural joint damage in participants with active rheumatoid arthritis who had an inadequate clinical response to methotrexate. Participants were randomized to receive rituximab 500 mg intravenously (iv), rituximab 1000 mg iv, or placebo iv on days 1 and 15 every 24 weeks in the main study; all participants received concomitant methotrexate at a stable dose of 12. 5-25 mg/week throughout the study. Further courses of rituximab were provided to eligible participants. Structural joint damage was assessed by magnetic resonance imaging (MRI) at baseline and at intervals during the study.

Clinical Details

Official title: A Randomized, Placebo Controlled, Multicenter Clinical Study Investigating Efficacy of Rituximab in the Inhibition of Joint Structural Damage Assessed by Magnetic Resonance Imaging in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate

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

Primary outcome: Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24

Secondary outcome:

Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52

Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52

Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52

Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52

Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52

Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52

Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52

Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52

Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52

Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52

Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52

Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52

Percentage of Participants Achieving a Major Clinical Response at Week 52

Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures

Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52

Adverse Events (AEs), Laboratory Parameters, C-reactive Protein, ESR.

Detailed description: There were 3 phases in the study: A 52 week long main study, a study extension phase, and a 48 week long safety follow-up phase. The first course of treatment with placebo or rituximab was initiated on Day 1 of the 52 week long main study. A second course of treatment was initiated after Week 24, if the participant met eligibility criteria. After Week 52, eligible participants received further treatment courses at intervals ≥ 6 months in the study extension phase. No treatments were administered in the safety follow-up phase. Participants had to meet the following eligibility criteria to receive rituximab in the study extension phase.

- Minimum of 24 weeks had passed since the first infusion of the last course of study

medication.

- C-reactive protein-based Disease Activity Score 28 (DAS28-CRP) ≥ 2. 6.

- Absolute neutrophil count not below 1. 5 x 103/μL.

- Patient had not developed contraindications for receiving rituximab, such as:

1. Any new or uncontrolled concomitant disease such as, but not limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders. 2. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection. 3. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization, or treatment with iv anti-infectives within 4 weeks prior to infusion or completion of oral anti-infectives within 2 weeks prior to infusion.

- Patient was not pregnant or breast feeding.

- Patients who entered the study and were found to be hepatitis B surface antigen (HBsAg)

negative, hepatitis B core antibody (HBcAb) positive, were to be negative for hepatitis B viral DNA (< 29 IU/mL) and were to have aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2. 5 x upper limit of normal (ULN) results within the last 12 weeks.

Eligibility

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult patients, 18-80 years of age.

- Active rheumatoid arthritis for ≥ 3 months and ≤ 10 years.

- Evidence of erosive disease and/or clinical synovitis in a signal joint.

- Inadequate response to 12. 5-25 mg/week methotrexate for ≥ 12 weeks.

Exclusion Criteria:

- Rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid

arthritis. - Any surgical procedure within 12 weeks prior to baseline.

- Previous treatment with a biologic agent or with a B cell modulating or cell

depleting therapy.

Locations and Contacts

Buenos Aires C1280AEB, Argentina

Brno 625 00, Czech Republic

Ceské Budejovice 370 01, Czech Republic

Praha 128 50, Czech Republic

Hillerod 3400, Denmark

Hvidovre 2650, Denmark

København 2100, Denmark

Tallinn 13419, Estonia

Tallinn 11312, Estonia

Montpellier 34295, France

Nice 06202, France

Orleans 45032, France

Toulouse 31059, France

Bad Aibling 83043, Germany

Berlin 10117, Germany

Dresden 01307, Germany

Erlangen 91054, Germany

Halle 06120, Germany

Hannover 30625, Germany

Athens 115 27, Greece

Patras 265 04, Greece

Thessaloniki 54636, Greece

Riga 1002, Latvia

Riga 1038, Latvia

Vilnius LT-08661, Lithuania

Amsterdam 1105 AZ, Netherlands

Oslo 0370, Norway

Bucharest 020475, Romania

Cluj-napoca 400006, Romania

Kazan 420097, Russian Federation

Moscow 115522, Russian Federation

Saint-Petersburg 195067, Russian Federation

Voronezh 394066, Russian Federation

Belgrade 11000, Serbia

Niska Banja 18250, Serbia

Barcelona 08003, Spain

Barcelona 08907, Spain

Madrid 28046, Spain

Malaga 29010, Spain

Sevilla 41009, Spain

Valencia 46017, Spain

Bern 3010, Switzerland

Adana 01330, Turkey

Ankara 06018, Turkey

Istanbul 34098, Turkey

Izmir 35100, Turkey

Goiania, GO 74110010, Brazil

Winnipeg, Manitoba R3E0W3, Canada

St John's, Newfoundland and Labrador A1A 5E8, Canada

Ottawa, Ontario K1H 1A2, Canada

Ottawa, Ontario K2G 6E2, Canada

Toronto, Ontario M4N 3M5, Canada

Curtiba, PR 80030-110, Brazil

Montreal, Quebec H1T 2M4, Canada

Montreal, Quebec H2L 1S6, Canada

Montreal, Quebec H3Z 2Z3, Canada

Quebec City, Quebec G1V 3M7, Canada

Porto Alegre, RS 90610-000, Brazil

Sao Paulo, SP 04023-900, Brazil

Saskatoon, Saskatchewan S7M 0Z9, Canada

Additional Information

Starting date: November 2007
Last updated: March 26, 2015

Page last updated: August 23, 2015

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