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

This study has been completed.
Sponsor:
Collaborators:
Oklahoma Medical Research Foundation
Genentech, Inc.
Information provided by (Responsible Party):
Gaylis, Norman B., M.D.
ClinicalTrials.gov Identifier:
NCT00425932
First received: January 22, 2007
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of Rituximab on Magnetic Resonance Imaging Evidence of Synovitis and Bone Lesions in Patients With Moderate or Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Gaylis, Norman B., M.D.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks. [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: February 2007
Study Completion Date: November 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00425932

Locations
United States, Florida
Guillermo Valenzuela MD
Fort Lauderdale, Florida, United States, 33324
Drs. Charles Kahn and Wayne Riskin
Hollywood, Florida, United States, 33021
Arhtritis & Rheumatic Disease Specialties
Miami, Florida, United States, 33180
United States, Kansas
Arthritis and Rheumatology Clinics of Kansas
Wichita, Kansas, United States, 67220
United States, Oklahoma
McBride Clinic Orthopedic Center
Oklahoma City, Oklahoma, United States, 73103
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Gaylis, Norman B., M.D.
Oklahoma Medical Research Foundation
Genentech, Inc.
Investigators
Principal Investigator: Norman B Gaylis, MD Arthritis & Rheumatic Disease Specialties
Principal Investigator: Ewa Olech, M.D. Oklahoma Medical Research Foundation
  More Information

No publications provided by Gaylis, Norman B., M.D.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gaylis, Norman B., M.D.
ClinicalTrials.gov Identifier: NCT00425932     History of Changes
Other Study ID Numbers: U3900s
Study First Received: January 22, 2007
Last Updated: August 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Gaylis, Norman B., M.D.:
Magnetic Resonance Imaging
Rituximab
Low Field MRI
Biomarkers

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014