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

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Jim Rosenbaum, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00415506
First received: December 21, 2006
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Scleritis
Orbital Disease
Drug: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PhaseI/II Prospective, Randomized, Dose-Ranging Pilot Study of Rituximab in the Treatment of Refractory Scleritis and Non-Infectious Orbital Inflammation

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Reduction of Medications [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 20
Study Start Date: January 2007
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Scleritis
Subjects with Scleritis
Drug: Rituximab
Two 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen.
Experimental: Orbital Inflammation
Subjects with Orbital Inflammation
Drug: Rituximab
Two 500 or 1000mg infusions over 2 weeks with the option of retreating after 6 months if initial improvement was seen.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • 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 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)
  • 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
  • Lack of peripheral venous access
  • History of drug, alcohol, or chemical abuse within 6 months prior to screening
  • Pregnancy (a negative serum pregnancy for all women of childbearing potential at screening and negative urine pregnancy test prior to each infusion) or lactation
  • Concomitant or previous malignancies, with the exception of curatively resected non-melanoma skin carcinomas or carcinoma in situ of the cervix
  • History of psychiatric disorder that would interfere with normal participation in this protocol
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Inability to comply with study and follow-up procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00415506

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Genentech
Investigators
Principal Investigator: James T Rosenbaum, MD Oregon Health and Science University
Study Director: Eric B Suhler, MD Oregon Health and Science University
  More Information

No publications provided by Oregon Health and Science University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jim Rosenbaum, Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT00415506     History of Changes
Other Study ID Numbers: e1529
Study First Received: December 21, 2006
Results First Received: May 20, 2013
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Inflammation
Scleritis
Orbital Diseases
Pathologic Processes
Scleral Diseases
Eye Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014