- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00424151
Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy
October 4, 2010 updated by: Silkiss, Rona Z., M.D., FACS
Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy Phase I/II
This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
Graves' Dysthyroid ophthalmopathy is an autoimmune disease characterized by inflammatory changes of the periocular and orbital region often in association with an underlying thyroid abnormality.
These changes can be extremely debilitating and may lead to visual loss.
Attempts at limiting or reversing the phenotypic expression of Graves' ophthalmopathy through aggressive orbital decompression surgery or targeting the inflammatory disease, using high dose systemic corticosteroids and/or orbital radiotherapy, have been limited to date by treatment ineffectiveness and co-morbidities.
Selective B-cell depletion therapy offers a potential treatment alternative.
This study is designed to treat patients with Graves' disease with Rituximab in an attempt to prevent or reverse the physically deforming and debilitating consequences of this disease.
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Oakland, California, United States, 94609
- Rona Z. Silkiss, MD, FACS
-
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New York
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New York, New York, United States, 10021
- Simeon A. Lauer, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients eighteen years of age or older.Diagnosed with Graves' dysthyroid ophthalmopathy within one year of presentation.
- Manifest significant ophthalmic findings of active Graves' disease. (Clinical activity score 4 or greater)
- Evidence of thyroid abnormality (hyper or hypo thyroid) prior to thyroid treatment
- Elevated thyroid stimulating immunoglobulin, antithyroid peroxidase antibody or antithyroglobulin antibody.
Exclusion Criteria:
Long standing chronic disease. (greater than one year) History of ineffective prior orbital irradiation. Clinical activity score of less than 4.
- ANC < 1.5 x 103
- Hemoglobin: < 8.5 gm/dL
- Platelets: < 100,000/mm
- AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
- IgG: < 5.6 mg/dl and IgM: < .55 mg/dl
- 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
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
- Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac, including significant or uncontrolled arrhythmia, or pulmonary disease (including obstructive pulmonary disease)
- History of systemic lupus erythematosis
- 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
-
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Clinical response to treatment, alteration in immunoglobulin levels
Time Frame: One year post infusion
|
One year post infusion
|
To assess the safety and tolerability of Rituximab in Graves' dysthyroid disease up to 24 weeks. Adverse and serious adverse events during the study period, reasonably or probably related to Rituximab, will be assessed at each study visit up to 12 month
Time Frame: One year
|
One year
|
Efficacy:
Time Frame: One year after treatment
|
One year after treatment
|
A significant (25%) reduction in progression of Thyroid Associated Ophthalmopathy or disease activity as measured by the thyroid associated ophthalmopathy scale (University of British Columbia Thyroid Orbitopathy Inflammatory Score) up to 24 weeks.
Time Frame: One year
|
One year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate for a reduction in disease activity as measured by:
Time Frame: One year
|
One year
|
Reduction (25%) of elevated antibody levels- serum thyroid stimulating immunoglobulin (TSI), antithyroidperoxidase antibody (TPO) or antithyroglobulin levels at 24 weeks.
Time Frame: One year
|
One year
|
MRI of the orbit with coronal and axial views to evaluate evidence of optic nerve crowding, muscle size reduction or decreased proptosis during treatment and follow up interval at 24 weeks.
Time Frame: Six months
|
Six months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Rona Z Silkiss, MD, California Pacific Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2006
Primary Completion (Actual)
March 1, 2009
Study Completion (Actual)
March 1, 2009
Study Registration Dates
First Submitted
January 17, 2007
First Submitted That Met QC Criteria
January 17, 2007
First Posted (Estimate)
January 18, 2007
Study Record Updates
Last Update Posted (Estimate)
October 6, 2010
Last Update Submitted That Met QC Criteria
October 4, 2010
Last Verified
October 1, 2010
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Genetic Diseases, Inborn
- Thyroid Diseases
- Eye Diseases, Hereditary
- Graves Disease
- Exophthalmos
- Orbital Diseases
- Goiter
- Hyperthyroidism
- Eye Diseases
- Graves Ophthalmopathy
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- U4126s
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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