Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00578305
First received: December 19, 2007
Last updated: December 8, 2014
Last verified: December 2014

December 19, 2007
December 8, 2014
November 2007
May 2013   (final data collection date for primary outcome measure)
Changes in MRI bone erosion score from baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change in MRI bone erosion score between baseline and week 24.
Complete list of historical versions of study NCT00578305 on ClinicalTrials.gov Archive Site
  • Change from baseline in MRI erosion, synovitis and osteitis [ Time Frame: Week 12, 24 and 52 ] [ Designated as safety issue: No ]
  • DAS 28-CRP, ACR 20/50/70, and HAQ. [ Time Frame: Week 24 and 52 ] [ Designated as safety issue: No ]
  • AEs, laboratory parameters, C-reactive protein, ESR. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Efficacy: Change from baseline in MRI erosion, synovitis and osteitis; DAS28-CRP, ACR 20/50/70 and HAQ at weeks 24 and 52. Safety: AEs, laboratory parameters, C-reactive protein, ESR.
Not Provided
Not Provided
 
A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate
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

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.

There were 3 phases in the study: A 52 week long main study, a ??? week long 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.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Rheumatoid Arthritis
  • Drug: Rituximab
    Rituximab was supplied as a sterile liquid for iv administration.
    Other Names:
    • MabThera®
    • Rituxan®
  • Drug: Placebo
    Placebo was supplied as a sterile liquid in single-use vials for iv administration.
  • Drug: Methylprednisolone
  • Drug: Methotrexate
  • Drug: Folic acid or folate
  • Experimental: Rituximab 500 mg
    Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
    Interventions:
    • Drug: Rituximab
    • Drug: Methylprednisolone
    • Drug: Methotrexate
    • Drug: Folic acid or folate
  • Experimental: Rituximab 1000 mg
    Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
    Interventions:
    • Drug: Rituximab
    • Drug: Methylprednisolone
    • Drug: Methotrexate
    • Drug: Folic acid or folate
  • Placebo Comparator: Placebo
    Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
    Interventions:
    • Drug: Placebo
    • Drug: Methylprednisolone
    • Drug: Methotrexate
    • Drug: Folic acid or folate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
185
May 2013
May 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Brazil,   Canada,   Czech Republic,   Denmark,   Estonia,   France,   Germany,   Greece,   Latvia,   Lithuania,   Netherlands,   Norway,   Romania,   Russian Federation,   Serbia,   Spain,   Switzerland,   Turkey
Former Serbia and Montenegro,   United Kingdom
 
NCT00578305
MA21056
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP