Trial of Rituximab for Graves' Ophthalmopathy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rebecca Bahn, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00595335
First received: January 1, 2008
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

This study is being done to investigate the effects (good and bad) of Rituximab for the treatment of an autoimmune eye disease called Graves' ophthalmopathy. This disease has proven to be difficult to treat. Rituximab is a monoclonal antibody that depletes a line of cells (B lymphocytes CD20 positive) involved in the autoimmune response. The study hypotheses is that rituximab is effective in the treatment of patients with moderate to severe active Graves' ophthalmopathy.


Condition Intervention Phase
Thyroid-associated Ophthalmopathy
Drug: Rituximab
Drug: IV saline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2/3 Study of Rituximab for Graves' Ophthalmopathy

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Improvement in Clinical Activity Score by 2 or more points [ Time Frame: 2,4,6 and 12 months after the first infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Decrease in disease severity [ Time Frame: 2,4,6 and 12 months after first infusion ] [ Designated as safety issue: No ]
  • Decrease in proptosis by ≥2 mm [ Time Frame: 2,4,6 and 12 months after first infusion ] [ Designated as safety issue: No ]
  • Decrease in lid aperture width by ≥3 mm [ Time Frame: 2,4,6 and 12 months after first infusion ] [ Designated as safety issue: No ]
  • Improvement in extraocular motility by ≥8 degrees [ Time Frame: 2,4,6 and 12 months after first infusion ] [ Designated as safety issue: No ]
  • Improvement in a GO-specific quality of life score of ≥ 6 points [ Time Frame: 2,4,6 and 12 months after first infusion ] [ Designated as safety issue: No ]
  • Failure rate, defined as need for additional therapy (excluding cosmetic surgery) for the eye disease [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Composite of decrease of CAS ≥ 2 points and no need for additional therapy for the eye disease versus either CAS decrease of < 2 points or need for additional therapy [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: April 2008
Study Completion Date: September 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Rituximab 1000 mg IV twice at 2-week intervals
Drug: Rituximab
15 patients will receive 2 infusions of rituximab (1000 mg IV), two weeks apart
Other Names:
  • Rituxan@
  • MabThera@
Placebo Comparator: Saline
Saline IV twice at 2-week intervals
Drug: IV saline
15 patients will receive 2 infusions if saline IV, 2 weeks apart

Detailed Description:

Detailed Description: Before any treatment is given, careful eye and thyroid physical examinations will be performed and the patients will have several thyroid blood tests, a test to count the white cells in the blood, and a CT scan of the head and eyes. A close-up photograph of the face will be taken and patients will be given a short questionnaire about how their eyes are feeling and how the eye disease is affecting their quality of life. Each study subject will receive either 2 infusions of rituximab (each 1000 mg; given 2 weeks apart) or 2 intravenous infusions of saline. Patients will return to Rochester 2 weeks after the first intravenous infusion in order to receive the second infusion. They will then return to Rochester four more times; 2 months apart for the first 3 return visits (weeks 8, 16 and 24 following the first infusion) and 6 months later (approximately 52 weeks following the first infusion) for the final visit to have the same blood tests performed. The CT scan will be repeated at 52 weeks. Patients will be assigned to one of these two groups in a random manner (like flipping a coin) and neither they nor the physicians will know until the study is completed whether they received saline or the study drug. Travel and lodging costs for the 4 return visits up to $2,750 with receipts will be reimbursed and all study-related medical costs following enrollment will be covered.Remuneration of $250.00 will be offered at the end of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients with clinical activity score (CAS) of ≥4 and moderate to severe disease severity, as defined by NOSPECS score
  • euthyroid for at least 6-8 weeks
  • no immediate need for decompression surgery

Exclusion Criteria:

  • corticosteroid use in the preceding 4 weeks
  • HIV, hepatitis C or hepatitis B infections
  • denied consent for HIV or hepatitis testing
  • mild or inactive Graves' ophthalmopathy
  • orbital radiotherapy within 18 months or orbital surgery within the past year
  • absolute neutrophil count < 1,500/mm3
  • pregnant or nursing patients
  • coronary artery disease, congestive heart failure, significant arrhythmias, significant infection or immunodeficiency, other serious illnesses
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00595335

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Rebecca Bahn
Investigators
Principal Investigator: Rebecca S Bahn, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Rebecca Bahn, Professor of Medicine, Consultant in Endocrinology, Mayo Clinic, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00595335     History of Changes
Other Study ID Numbers: 06-006130, R01DK077814, NIH RO1DK077814-01
Study First Received: January 1, 2008
Last Updated: September 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Thyroid-associated ophthalmopathy
Rituximab
Proptosis

Additional relevant MeSH terms:
Eye Diseases
Thyroid Diseases
Graves Ophthalmopathy
Endocrine System Diseases
Eye Diseases, Hereditary
Graves Disease
Exophthalmos
Orbital Diseases
Goiter
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 22, 2014