Rituximab Treatment of Graves' Dysthyroid Ophthalmopathy

NCT00424151 | Completed Phase 1

• 1 other identifier: U4126s
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Graves' Dysthyroid Ophthalmopathy; Thyroid Related Orbitopathy

Keywords

Graves' Disease; Dysthyroid Ophthalmopathy; Thyroid related orbitopathy

Outcome Measures

Primary Outcomes (4)

• Clinical response to treatment, alteration in immunoglobulin levels

  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

  One year

• Efficacy:

  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.

  One year

Secondary Outcomes (3)

• To evaluate for a reduction in disease activity as measured by:

  One year

• Reduction (25%) of elevated antibody levels- serum thyroid stimulating immunoglobulin (TSI), antithyroidperoxidase antibody (TPO) or antithyroglobulin levels at 24 weeks.

  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.

  Six months

Interventions

Rituximab DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Silkiss, Rona Z., M.D., FACS: lead
• Lauer, Simeon, M.D.: collaborator
• Reier, Alice M.D.: collaborator
• Coleman, Morton M.D.: collaborator

Study Sites (2)

Rona Z. Silkiss, MD, FACS

Oakland, California, 94609, United States

Location

Simeon A. Lauer, MD

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Graves Disease; Graves Ophthalmopathy

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rona Z Silkiss, MD

  California Pacific Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV

Study Record Dates

• First Submitted: January 17, 2007
• First Posted: January 18, 2007
• Study Start: December 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: October 6, 2010

Record last verified: 2010-10

Locations

US (2)