Rituximab in the Treatment of Scleritis and Non-Infectious Orbital Inflammation

NCT00415506 | Completed Phase 1 Results

• 1 other identifier: e1529
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Scleritis; Orbital Disease

Outcome Measures

Primary Outcomes (2)

• Reduction of Medications

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

  24 Weeks

• 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.

  24 weeks

Study Arms (2)

Scleritis

EXPERIMENTAL

Subjects with Scleritis

Drug: Rituximab

Orbital Inflammation

EXPERIMENTAL

Subjects with Orbital Inflammation

Drug: Rituximab

Interventions

Rituximab DRUG

Two 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen.

Orbital Inflammation; Scleritis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)
• Receipt of a live vaccine within 4 weeks prior to randomization
• Previous Treatment with Rituximab (MabThera® / Rituxan®)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening
• Unstable steroid dose in the past 4 weeks

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Suhler EB, Lim LL, Beardsley RM, Giles TR, Pasadhika S, Lee ST, de Saint Sardos A, Butler NJ, Smith JR, Rosenbaum JT. Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial. JAMA Ophthalmol. 2014 May;132(5):572-8. doi: 10.1001/jamaophthalmol.2013.8179.

  PMID: 24652467 DERIVED

MeSH Terms

Conditions

Scleritis; Orbital Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Scleral Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Eric B. Suhler
• Organization: Oregon Health & Science University

suhlere@ohsu.edu

503-494-5023

Study Officials

• James T Rosenbaum, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

• Eric B Suhler, MD

  Oregon Health and Science University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2006
• First Posted: December 25, 2006
• Study Start: January 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: August 16, 2013
• Results First Posted: August 8, 2013

Record last verified: 2013-08

Locations

US (1)