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Impact of Rituximab on MRI Evidence of Disease Activity in Patients With Moderate to Severe Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00425932
Recruitment Status : Completed
First Posted : January 24, 2007
Last Update Posted : August 22, 2013
Sponsor:
Collaborators:
Oklahoma Medical Research Foundation
Genentech, Inc.
Information provided by (Responsible Party):
Gaylis, Norman B., M.D.

Tracking Information
First Submitted Date  ICMJE January 22, 2007
First Posted Date  ICMJE January 24, 2007
Last Update Posted Date August 22, 2013
Study Start Date  ICMJE February 2007
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2008)
The primary endpoint fo the trial is change in 1.5 Tesla MRI erosion score (RAMRIS system) from baseline to Week 24. [ Time Frame: 24 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2007)
The primary endpoint fo the trial is change in 1.5 Tesla MRI erosion score (RAMRIS system) from baseline to Week 24.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2008)
  • Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12. [ Time Frame: 12 weeks ]
  • Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24. [ Time Frame: 24 weeks ]
  • Change from Baseline in 1.5 Tesla MRI bone edema, bone erosion and total score (RAMRIS system) at Week 12 and Week 48. [ Time Frame: 12 and 48 weeks ]
  • Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI. [ Time Frame: 48 weeks ]
  • Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48. [ Time Frame: 24 and 48 weeks ]
  • Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48. [ Time Frame: 24 and 48 weeks ]
  • ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48. [ Time Frame: 24 and 48 weeks ]
  • Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks. [ Time Frame: 24 and 48 weeks ]
  • Difference between relative results from conventional high-field strength 1.5 Tesla MRI and 0.2 Tesla dedicated extremity MRI in detection and grading of bone erosions, bone edema, and synovitis at Baseline and in Week 12,24, and 48 (C-scan validation). [ Time Frame: 12, 24 and 48 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2007)
  • Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12.
  • Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24.
  • Change from Baseline in 1.5 Tesla MRI bone edema, bone erosion and total score (RAMRIS system) at Week 12 and Week 48.
  • Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI.
  • Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48.
  • Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48.
  • ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48.
  • Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks.
  • Difference between relative results from conventional high-field strength 1.5 Tesla MRI and 0.2 Tesla dedicated extremity MRI in detection and grading of bone erosions, bone edema, and synovitis at Baseline and in Week 12,24, and 48 (C-scan validation).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Rituximab on MRI Evidence of Disease Activity in Patients With Moderate to Severe Rheumatoid Arthritis
Official Title  ICMJE Impact of Rituximab on Magnetic Resonance Imaging Evidence of Synovitis and Bone Lesions in Patients With Moderate or Severe Rheumatoid Arthritis
Brief Summary The purpose of this study is to further investigate rituximab in the treatment of rheumatoid arthritis and to evaluate magnetic resonance imaging of the joints as a possible method to improve the evaluation of treatments.
Detailed Description

Rituximab is a monoclonal antibody that has been approved for the treatment of non-Hodgkin's B cell lymphoma (a type of cancer) and for certain patients with rheumatoid arthritis (RA) by the Food and Drug Administration (FDA). To date, more than 1000 subjects with rheumatoid arthritis have received rituximab in clinical studies.

Magnetic resonance imaging (MRI) is a modern and sensitive method of looking at joints in people with rheumatoid arthritis. It uses a magnetic field to create an image. The MRI takes an image in 3 dimensions and this provides a better picture for a physician to see more details.

There are two treatment groups in this study with equal numbers of patients assigned to each group. All the patients will receive their baseline Methotrexate and two intravenous infusions 2 weeks apart of one of the following:

  • 1000 mg rituximab or
  • placebo. Patients outcomes will be compared between the 2 groups. After week 24 (open label phase), the patients will receive rituximab if rheumatoid arthritis remains active.

All the patients will have MRI of their dominant hand and wrist with and without gadolinium performed at baseline, 12, 24 and 48 weeks on 1.5 Tesla MRI . Some patients will also have additional MRI of the same hand and wrist without gadolinium at the same time points on 0.2 Tesla MRI. Comparison of the images from the two machines will be performed.

Various blood biomarkers will also be examined, compared between the 2 treatment groups and correlated with the MRI results.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE Biological: Rituximab
At Week 24 or any time up to Week 48 if the Patient DAS 28 > 2.6 patients will be retreated with 1000 mg IV at Day and Day 15.
Other Name: Rituxan
Study Arms  ICMJE
  • No Intervention: Rituximab/Placebo
    Patients will be randomized at Baseline to either Placebo or Rituximab. At Week 24 and up to Week 48 if patient DAS28 score is >2.6, patient will be retreated with open label Rituximab.
  • Active Comparator: Open Label
    At Week 24 or any time up to Week 48 if the Patient DAS 28 > 2.6 patients will be retreated with 1000 mg IV at Day and Day 15.
    Intervention: Biological: Rituximab
Publications * Peterfy CG, Olech E, DiCarlo JC, Merrill JT, Countryman PJ, Gaylis NB. Monitoring cartilage loss in the hands and wrists in rheumatoid arthritis with magnetic resonance imaging in a multi-center clinical trial: IMPRESS (NCT00425932). Arthritis Res Ther. 2013 Mar 20;15(2):R44. doi: 10.1186/ar4202.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2007)
60
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Able and willing to give written informed consent
  • Age 18-80 years
  • Must have active rheumatoid arthritis for at least 12 weeks, but no more than 5 years.
  • Must be receiving treatment on an outpatient basis
  • Must have > 8 tender and swollen joints
  • Must have negative serum pregnancy test
  • Must have an inadequate response to MTX
  • Must have elevated serology parameters
  • Must have Positive RF or anti-CCP antibody, or radiographic evidence of at least one joint with definite erosion attributable to RA.
  • Stable use of Corticosteroids is permitted
  • Stable use of NSAIDs is permitted

Exclusion Criteria:

  • History of or current inflammatory joint disease
  • Functional class IV
  • Any surgical procedure within 12 weeks
  • Lack of peripheral venous access.
  • Pregnancy or breast feeding.
  • Significant cardiac or pulmonary disease.
  • Evidence of significant uncontrolled concomitant disease
  • Positive HIV
  • Known active infection of any kind
  • History of deep space/tissue infection
  • History of recurrent significant infection
  • Concomitant malignancies or previous malignancies
  • Any neurological, vascular or systemic disorder
  • History of drug, alcohol, or chemical abuse
  • Inability to comply with study and follow-up procedures
  • History of a severe allergic or anaphylactic reaction to a biologic agent
  • Previous treatment with more than one biologic agent for RA. Patients must not have received a biologic agent within 2 months prior to the Baseline visit, except for etanercept, abatacept and anakinra for which a one month washout prior to Baseline visit is acceptable
  • Previous treatment with an anti-alpha 4 integrin antibody or co-stimulation modulator.
  • Previous treatment with any cell depleting therapies.
  • Treatment with any investigational agent within 28 days
  • Receipt of a live/attenuated vaccine within 28 days
  • Ongoing use of high dose steroids (>10mg/day)
  • Inra-articular or parental glucocorticoids within 4 weeks prior to baseline.
  • Intolerance or contraindications to i.v. glucocorticoids.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00425932
Other Study ID Numbers  ICMJE U3900s
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Gaylis, Norman B., M.D.
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Gaylis, Norman B., M.D.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Oklahoma Medical Research Foundation
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Norman B Gaylis, MD Arthritis & Rheumatic Disease Specialties
Principal Investigator: Ewa Olech, M.D. Oklahoma Medical Research Foundation
PRS Account Gaylis, Norman B., M.D.
Verification Date August 2013

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