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

Gaylis, Norman B., M.D.

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Biological: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00425932

U3900s

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups

Rituximab/Placebo

No Intervention group

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.

Open Label

Active Comparator group

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.

Treatment:

Biological: Rituximab