Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy

Thyroid Related Orbitopathy Clinical Trial

Official title:

Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy Phase I/II

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424151
• Other study ID #: U4126s
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 17, 2007
• Last updated: October 4, 2010
• Start date: December 2006
• Est. completion date: March 2009

Study information

• Verified date: October 2010
• Source: Silkiss, Rona Z., M.D., FACS
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Graves' Dysthyroid Ophthalmopathy
• Thyroid Related Orbitopathy

Intervention

Drug:
• Rituximab

Locations

Country	Name	City	State
United States	Simeon A. Lauer, MD	New York	New York
United States	Rona Z. Silkiss, MD, FACS	Oakland	California

Sponsors (4)

Lead Sponsor	Collaborator
Silkiss, Rona Z., M.D., FACS	Coleman, Morton M.D., Lauer, Simeon, M.D., Reier, Alice M.D.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response to treatment, alteration in immunoglobulin levels		One year post infusion	No
Primary	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		One year	Yes
Primary	Efficacy:		One year after treatment	No
Primary	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.		One year	No
Secondary	To evaluate for a reduction in disease activity as measured by:		One year	No
Secondary	Reduction (25%) of elevated antibody levels- serum thyroid stimulating immunoglobulin (TSI), antithyroidperoxidase antibody (TPO) or antithyroglobulin levels at 24 weeks.		One year	No
Secondary	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.		Six months	No