Orbital Disease, Scleritis
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of Rituximab in refractory scleritis and non-infectious orbital inflammation.
Interventions
DRUGRituximab
Two 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen.
Sponsors
Genentech, Inc.
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Adequate renal function as indicated by normal BUN and creatinine levels.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of Medications | 24 Weeks | Reduction (decrease in dosage) of systemic corticosteroids or immunosuppressive therapy by at least 50% by 24 weeks. |
| Improved Control of Inflammation | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from January 2007 through March of 2010. Subjects were recruited from the investigator's medical clinic.
Pre-assignment details
Of the 20 subjects enrolled, two subjects had both orbital disease and scleritis. These two subjects were followed for both indications.
Participants by arm
| Arm | Count |
|---|---|
| Scleritis Subjects with Scleritis | 12 |
| Orbital Inflammation Subjects with Orbital Inflammation | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Scleritis | Orbital Inflammation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 8 Participants | 20 Participants |
| Region of Enrollment United States | 12 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 |
Outcome results
Primary
Improved Control of Inflammation
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.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Scleritis | Improved Control of Inflammation | 9 participants |
| Orbital Inflammation | Improved Control of Inflammation | 7 participants |
Primary
Reduction of Medications
Reduction (decrease in dosage) of systemic corticosteroids or immunosuppressive therapy by at least 50% by 24 weeks.
Time frame: 24 Weeks
Population: Only patients currently on systemic corticosteroids were analyzed for this outcome point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Scleritis | Reduction of Medications | 5 participants |
| Orbital Inflammation | Reduction of Medications | 4 participants |