A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.

NCT00502853 | Completed Phase 4 Results

• 1 other identifier: ML21081
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This single arm study will measure the effect of MabThera in combination with methotrexate on the progression of synovitis, the extent of bone marrow edema, and the number of erosions in the wrist and hand of patients with rheumatoid arthritis, using a new MRI technique. Patients will receive MabThera 1000mg i.v. on days 1 and 15, in combination with a stable dosage of 10-25mg/week methotrexate throughout the duration of the study. Further courses of MabThera will be provided to eligible patients. MRI will be performed 1-2 weeks before treatment initiation, and repeated 1 and 6 months after the first MabThera infusion. The anticipated time on study treatment is 1-2 years, and the target sample size is \<100 individuals.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (5)

• Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score

  Extension and degree of synovitis in wrist according to RAMRIS score developed by OMERACT. Synovitis is an area in synovial compartment that shows above normal post-gadolinium enhancement of a thickness greater than width of normal synovium. Synovitis is assessed in 3 wrist regions (distal radioulnar joint; radiocarpal joint; intercarpal and carpometacarpal joints) and in each metacarpophalangeal (MCP) joint. 1st carpometacarpal joint and 1st MCP joint are not scored. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score=the sum of the individual scores (3 wrist regions \[range 0-9\] or 4 MCP joints \[range 0-12\]) for an overall range of 0-21, where 0=no damage and maximum score \[9, 12, or 21\]=most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.

  Baseline, Week 4, and Week 24

• OMERACT RAMRIS Bone Edema Score

  Extension and degree of bone edema in the wrist according to the RAMRIS score developed by OMERACT. Bone edema is a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) is scored separately. The scale of 0-3 was based on the proportion of bone with edema, as follows: 0=no edema; 1=1 percent (%) to 33% of bone was edematous; 2 = 34%-66% of bone was edematous; and 3= 67%-100% of bone was edematous. Total bone edema score=sum of the individual scores for an overall range of 0-69, where 0=no edema and 69=most severe edema. Change in bone edema = follow-up bone edema score - baseline score.

  Baseline, Weeks 4 and 24

• OMERACT RAMRIS Erosion Score

  MRI bone erosion measures a sharply marginated bone lesion, with correct juxta-articular localization and typical signal characteristics, which is visible in 2 planes with a cortical break seen in at least 1 plane. Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) scored separately. Scale is 0-10 based on proportion of eroded bone compared to assessed bone volume (0=no erosion; 1=1%-10% of bone eroded; 2=11%-20%, etc). For long bones, assessed bone volume is from articular surface (or best estimated position if absent) to depth of 1 centimeter (cm); in carpal bones it is the whole bone. Total erosion score=sum of individual scores for an overall range of 0-230, where 0=no erosion and 230=most severe erosion. Change in erosion=Follow-up erosion score - baseline score.

  Baseline, Week 4, and Week 24

• Early Enhancement Rate (REE)

  A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints. In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI, i.e. Contrast-Enhanced Dynamic MRI (DCE-MRI). This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane. Numerical parameters used with this method are the slope in the initial phase (rate of early enhancement - REE) and its "steady state" condition (relative enhancement - RE). REE per second during the first 55 seconds was calculated according to the formula REE55 = (S55-S0)/(S0x55)x100%. The REE shows the slope of the curve of contrast uptake tangential to the α angle and is steeper if inflammation is higher.

  Baseline, Weeks 4 and 24

• Relative Enhancement (RE) Score

  A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints. In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI (DCE-MRI). This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane. Numerical parameters used with this method are the slope in the initial phase (REE) and its "steady state" condition (RE).

  Baseline, Weeks 4 and 24

Secondary Outcomes (17)

• Ritchie Articular Index Scores

  Baseline and Weeks 4, 12, and 24

• Health Assessment Questionnaire - Disability Index (HAQ-DI) Score

  Baseline and Weeks 4, 12, and 24

• Patient's Global Assessment of Pain

  Baseline and Weeks 4, 12, and 24

• DAS28 Score

  Baseline and Weeks 4, 12, and 24

• Erythrocyte Sedimentation Rate (ESR)

  Baseline and Weeks 4, 12, and 24

Study Arms (1)

1

EXPERIMENTAL

Drug: rituximab [MabThera/Rituxan]; Drug: Methotrexate

Interventions

rituximab [MabThera/Rituxan] DRUG

1000mg iv on days 1 and 15

1

Methotrexate DRUG

10-25mg/week

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patients, 18-75 years of age;
• rheumatoid arthritis for \>=3 months and \<=10 years;
• inadequate response to methotrexate (12.5-25mg/week) for \>=3 months;
• evidence of erosive disease and/or clinical synovitis in a signal joint.

You may not qualify if:

• autoimmune rheumatic diseases other than RA;
• surgical operations on bones/joints in 12 weeks prior to baseline visit;
• concomitant treatment with biologic agents;
• previous treatment with more than one biologic agent approved for RA, or with cell-depleting therapies.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Università Degli Studi Di Genova - Dimi; Reumatologia

Genoa, Liguria, 16132, Italy

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 18, 2007
• Study Start: October 25, 2007
• Primary Completion: July 23, 2010
• Study Completion: July 23, 2010
• Last Updated: August 16, 2017
• Results First Posted: March 12, 2015

Record last verified: 2017-06

Locations

IT (1)