Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy

Silkiss, Rona Z., M.D., FACS

Status and phase

Completed

Phase 2

Phase 1

Conditions

Thyroid Related Orbitopathy

Graves' Dysthyroid Ophthalmopathy

Treatments

Drug: Rituximab

Study type

Interventional

Funder types

Other

Identifiers

NCT00424151

U4126s

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.