A PhaseI/II Prospective, Randomized, Dose-Ranging Pilot Study of Rituximab in the Treatment of Refractory Scleritis and Non-Infectious Orbital Inflammation

Oregon Health and Science University1 site in 1 country20 target enrollmentJanuary 2007

ConditionsScleritis Orbital Disease

InterventionsRituximab

DrugsRituximab

Overview

Phase: Phase 1
Intervention: Rituximab
Conditions: Scleritis
Sponsor: Oregon Health and Science University
Enrollment: 20
Locations: 1
Primary Endpoint: Reduction of Medications
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the safety and tolerability of Rituximab in refractory scleritis and non-infectious orbital inflammation.

Registry

clinicaltrials.gov

Start Date

January 2007

End Date

March 2011

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Oregon Health and Science University

Responsible Party

Principal Investigator

Jim Rosenbaum

Professor

Oregon Health and Science University

Eligibility Criteria

Inclusion Criteria

•Patients with non-infectious scleritis or idiopathic orbital inflammatory disease requiring chronic immunosuppressive treatment for disease control.
•Intolerance, failure to respond to, or inability to taper below prednisone \> 10mg/day in addition to one systemic immunosuppressive (such as methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or chlorambucil).
•Patients must be on a stable dosage of prednisone and at least one steroid-sparing agent in the 30 days prior to screening/enrollment.
•Active disease will be defined using physician judgment and supported by patient and physician global ocular disease assessment of \> 5 cm on a 10cm visual analog scale anchored by the words "Inactive Eye Disease" at 0 cm point and "Extremely Active Eye Disease" at the 10cm point. Investigator discretion may apply in some cases.
•Selected patients who are on biological agents such as TNF blockers etanercept, infliximab and adalimumab with ongoing ocular disease are acceptable. There will be an 8 week washout period of etanercept and a 12 week washout period for infliximab and adalimumab before patients are dosed with rituximab.
•In patients with concomitant systemic autoimmune diseases including RA, SLE, Sjogrens, Wegener's granulomatosis the systemic disease must be sufficiently stable and not life threatening to allow tapering of steroids and/or immunosuppressive agents thus allowing assessment of ocular effect of rituximab.
•Adults of both genders \> 18 years old. There is no upper age limit as long as there are no other disqualifying health conditions.
•Have had a recent (\<3 months old) PPD skin test and are considered eligible according to the tuberculosis (TB) screening, eligibility assessment, and prevention rules defined in Appendix C.
•Screening laboratory test results should be acceptable to the Investigator prior to placing a patient on study drug.
•Must have a chest radiograph within 3 months prior to first infusion with no evidence of malignancy, infection or fibrosis.

Exclusion Criteria

•Untreated thyroid disease
•Organ threatening systemic disease as evidenced by rapidly progressive glomerulonephritis, pulmonary hemorrhage or respiratory failure, seizures or psychosis, progressive neuropathy or myopathy
•General Safety \& Laboratory Exclusion Criteria
•Patients will be excluded from the study based on the following criteria:
•Hemoglobin: \< 8.5 gm/dL
•Platelets: \< 100,000/mm
•AST or ALT \>2.5 x Upper Limit of Normal unless related to primary disease.
•Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
•History of positive HIV (HIV conducted during screening if applicable)
•Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)

Arms & Interventions

Scleritis

Subjects with Scleritis

Intervention: Rituximab

Orbital Inflammation

Subjects with Orbital Inflammation

Intervention: Rituximab

Outcomes

Primary Outcomes

Reduction of Medications

Time Frame: 24 Weeks

Reduction (decrease in dosage) of systemic corticosteroids or immunosuppressive therapy by at least 50% by 24 weeks.

Improved Control of Inflammation

Time Frame: 24 weeks

For patients with scleritis, disease activity as measured by a modified grading system first described by McCluskey et al. (McCluskey and Wakefield 1987; McCluskey and Wakefield 1991). Improvement in scleritis activity will be defined as a reduction in this grading score of 2 or more, or an overall score of 4 or less by 24 weeks. For patients with orbital inflammation, disease activity as measured by a modified grading system first devised by Werner (Werner 1977). Improvement in orbital inflammation will be defined as a reduction in this grading score of 2 or more, or an overall score of 3 or less.