Purpose of Study:
This project is being done to obtain information on the safety, tolerability, and effectiveness of a drug called TEPEZZA in the treatment of chronic (inactive) thyroid eye disease (TED). This drug was approved by the United States Food and Drug Administration (FDA) on 21 January 2020 for the treatment of thyroid eye disease. Previous research with TEPEZZA has been conducted on individuals with active thyroid eye disease and has shown improvements in eye symptoms including eye bulging. This research trial is evaluating treatment with TEPEZZA on chronic inactive TED.  

What is Thyroid Eye Disease (TED)?
People with Thyroid Eye Disease (TED) experience eye problems often associated with an overactive thyroid (Graves’ disease). The eye problems seen with TED include swelling, redness and discomfort of the eyelids and eye surface, increased tearing, thickening and pulling back of the eyelids, bulging of the eyes, squinting, and double vision. TED can threaten sight for a small proportion of patients. The natural history of TED involves an initial progressive worsening of signs and symptoms with visible signs of swelling known as the “active phase”, followed by an “inactive phase” where swelling may be decreased and no further worsening occurs, but the tissue around the orbit of the eye does not return to normal and therefore the eye problems remain. 

What is involved in this project?
Potential study participants must first be evaluated for eligibility by an ophthalmologist at the Medical College of Wisconsin/Froedtert Hospital Eye Institute. Research participants will make regular visits to the Eye Institute over the course of 7-14 months. After screening tests are performed to confirm eligibility, participants receive the study drug as a series of infusions into a vein.

Participants will be given one of two interventions as an infusion without knowing which one they are receiving. Participants will receive either TEPEZZA or a placebo (an infusion containing no real medicine). About two thirds (2/3) of patients taking part in this trial will receive TEPEZZA and one third (1/3) of patients will receive placebo.

After the initial series of infusions, if no improvement has been shown, the participant may be given open-label infusions of teprotumumab. 

Compensation: 
Research volunteers will receive a stipend of $75 for the completion of each study visit.

You may be eligible to participate in this study if you meet these criteria:

1. You are 18 years or older.
2. You have a diagnosis of stable, chronic (inactive) TED.
3. Patients must be euthyroid or with mild hypo- or hyperthyroidism.
4. The following previous treatments are not allowed:
   
   • Steroids (intravenous, oral, eye drops)
   • Rituximab (Rituxan or MabThera) within 12 months prior to first infusion
   • Tocilzumab (Actemra or Roacterma) within 6 months prior to first infusion
   • Non-steroid immunosuppressive agents within 3 months prior to first infusion
   • Previous treatment with TEPEZZA
   • Monoclonal antibody drugs
   • Use of an investigational agent within 60 days prior to first visit
     
     
5. No cancer within the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ)
6. Diabetes must be well controlled.
7. No plan for ophthalmic surgery.
8. Patients with inflammatory bowel disease, ulcerative colitis, or Crohn’s disease must be in clinical remission for at least 3 months prior to first visit.
9. No drug or alcohol abuse
10. No pregnant or lactating women.
11. No known hypersensitivity to any of the components of teprotumumab or monoclonal antibodies.

More Information:
Additional information about the HZNP-TEP-403 study can be found at ClinicalTrials.gov.
IRB Approval: PRO39536, 7/14/21