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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Gaylis, Norman B., M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Magnetic Resonance Imaging, Rituximab, Low Field MRI, Biomarkers

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Guillermo Valenzuela MD
  • Drs. Charles Kahn and Wayne Riskin
  • Arhtritis & Rheumatic Disease Specialties
  • Arthritis and Rheumatology Clinics of Kansas
  • McBride Clinic Orthopedic Center
  • Oklahoma Medical Research Foundation

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Rituximab/Placebo

Open Label

Arm Description

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.

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.

Outcomes

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.

Secondary Outcome Measures

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).

Full Information

First Posted
January 22, 2007
Last Updated
August 21, 2013
Sponsor
Gaylis, Norman B., M.D.
Collaborators
Oklahoma Medical Research Foundation, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00425932
Brief Title
Impact of Rituximab on MRI Evidence of Disease Activity in Patients With Moderate to Severe Rheumatoid Arthritis
Official Title
Impact of Rituximab on Magnetic Resonance Imaging Evidence of Synovitis and Bone Lesions in Patients With Moderate or Severe Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gaylis, Norman B., M.D.
Collaborators
Oklahoma Medical Research Foundation, Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Magnetic Resonance Imaging, Rituximab, Low Field MRI, Biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab/Placebo
Arm Type
No Intervention
Arm Description
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.
Arm Title
Open Label
Arm Type
Active Comparator
Arm Description
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 Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Change from Baseline in 1.5 Tesla MRI synovitis score (RAMRIS system) at Week 12.
Time Frame
12 weeks
Title
Change from Baseline in 1.5 Tesla MRI bone edema and total score (RAMRIS system) at Week 24.
Time Frame
24 weeks
Title
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
Title
Proportion of patients at Week 48 without new bone erosions on 1.5 Tesla MRI.
Time Frame
48 weeks
Title
Change from baseline in total Genant modified Sharp score on conventional radiographs at Week 24 and 48.
Time Frame
24 and 48 weeks
Title
Change in Disease Activity Score (DAS 28) from Baseline to Week 24 and 48.
Time Frame
24 and 48 weeks
Title
ACR remission and responder rates (20%, 50%, &)%) at Week 24 and 48.
Time Frame
24 and 48 weeks
Title
Change from Baseline in functional assessments according to the HAQ scores at 24 and 48 Weeks.
Time Frame
24 and 48 weeks
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norman B Gaylis, MD
Organizational Affiliation
Arthritis & Rheumatic Disease Specialties
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ewa Olech, M.D.
Organizational Affiliation
Oklahoma Medical Research Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guillermo Valenzuela MD
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Drs. Charles Kahn and Wayne Riskin
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Arhtritis & Rheumatic Disease Specialties
City
Miami
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Arthritis and Rheumatology Clinics of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67220
Country
United States
Facility Name
McBride Clinic Orthopedic Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23514433
Citation
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.
Results Reference
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Impact of Rituximab on MRI Evidence of Disease Activity in Patients With Moderate to Severe Rheumatoid Arthritis

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