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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
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Rituximab
Drug: Placebo
Drug: Methylprednisolone
Drug: Methotrexate
Drug: Folic acid or folate
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Changes in MRI bone erosion score from baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 185
Study Start Date: November 2007
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Rituximab
Rituximab was supplied as a sterile liquid for iv administration.
Other Names:
  • MabThera®
  • Rituxan®
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.
Drug: Rituximab
Rituximab was supplied as a sterile liquid for iv administration.
Other Names:
  • MabThera®
  • Rituxan®
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.
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

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578305

  Show 60 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00578305     History of Changes
Other Study ID Numbers: MA21056
Study First Received: December 19, 2007
Last Updated: December 8, 2014
Health Authority: Latvia: State Agency of Medicines

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Folic Acid
Methotrexate
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Rituximab
Vitamin B Complex
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on March 03, 2015