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 52Change 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
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