A Study Evaluating TEPEZZA® Treatment in Patients With Chronic (Inactive) Thyroid Eye Disease

Study Overview
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Brief Summary
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The overall objective is to investigate the efficacy, safety and tolerability of TEPEZZA® in participants with chronic (inactive) TED (thyroid eye disease). Approximately 57 participants will be enrolled. There will be a treatment period (through Week 24) and a follow up period (where TEPEZZA will not be infused).

Detailed Description
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This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter trial. Participants will be screened for the trial within 4 weeks prior to Baseline (Day 1). Approximately 57 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 2:1 ratio to receive 8 infusions of TEPEZZA or placebo once every 3 weeks. All participants will enter a 24-week double-masked Treatment Period, during which trial drug will be infused on Day 1 (Baseline) and Weeks 3, 6, 9, 12, 15, 18 and 21 (with a final visit at Week 24 of the 24-week Treatment Period). At the end of the double-masked Treatment Period (Week 24), all patients will be assessed for treatment response. Non-responders may choose to receive 8 infusions of TEPEZZA in an open-label fashion q3W at Weeks 24, 27, 30, 33, 36, 39, 42 and 45.

Official Title
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A Phase 4, Randomized, Double-masked, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of TEPEZZA® in Treating Patients With Chronic (Inactive) Thyroid Eye Disease

Conditions
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Chronic (Inactive) Thyroid Eye Disease, Thyroid Eye Disease

Intervention / Treatment
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* Biological: TEPEZZA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Male or female at least 18 years old at Screening. Initial diagnosis of TED ≥2 years but <10 years prior to Screening. Clinical diagnosis of stable, chronic (inactive) TED, as determined by participant medical records indicating a Clinical Activity Score (CAS) ≤1 in both eyes for at least 1 year prior to Screening or all of the following: no progression in proptosis for at least 1 year prior to Screening if participant has history of diplopia due to TED, no progression in diplopia for at least 1 year prior to Screening no new inflammatory TED symptoms for at least 1 year prior to Screening CAS ≤1 at the Screening and Baseline Visits. Proptosis ≥3-mm increase from participant's Baseline (prior to diagnosis of TED), as estimated by treating physician and/or proptosis ≥3 mm above normal for race and gender. Participants must be euthyroid with the participant's Baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels <50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the trial. Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial. Diabetic participants must have HbA1c ≤8.0% at Screening. Participants with a history of inflammatory bowel disease, ulcerative colitis or Crohn's disease must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to screening and no planned surgery during the trial. Concomitant stable therapies for inflammatory bowel disease without modifications in the 3 months prior to Screening are allowed. Women of childbearing potential (including those with an onset of menopause <2 years prior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening, or not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (i.e., prior to each dose and throughout participant's participation); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of trial drug. Highly effective contraceptive methods (failure rate <1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, sexual abstinence and vasectomized partner. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. Exclusion Criteria: Decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect secondary to optic nerve involvement within the last 6 months. Corneal decompensation unresponsive to medical management in the study eye Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline. Prior orbital irradiation, orbital decompression in the study eye. Prior strabismus surgery. Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73 m2 at Screening. Use of any steroid (IV, oral, steroid eye drops) for the treatment of TED or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids and steroids used to treat infusion reactions. Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of trial drug or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of trial drug. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of trial drug. Any previous treatment with TEPEZZA, including previous enrollment in this trial or participation in a prior teprotumumab trial. Treatment with any mAb within 3 months prior to Screening. Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results. Use of an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial. Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). Pregnant or lactating women. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant. Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity reactions to mAbs. Poorly controlled human immunodeficiency virus infection or untreated or positive viral load for hepatitis C or hepatitis B infections. Any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TEPEZZA<br>8 infusions of TEPEZZA (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) with a final visit at Week 24 (Treatment Period) | Biological: TEPEZZA<br>* TEPEZZA is a fully human anti-IGF-1R mAb.TEPEZZA will be provided in single-dose 20mL glass vials as a freeze-dried powder.Each vial of TEPEZZA must be reconstituted with 10 mL of sterile water for injection. Reconstituted TEPEZZA solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration.TEPEZZA will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).<br>* Other names: HZN-001;|
| Placebo Comparator: Placebo<br>Placebo once every 3 weeks | Drug: Placebo<br>* Placebo (normal saline, 0.9% NaCl) solution will be administered in 100 mL or 250 mL infusion bags per weight based dosing volumes once every 3 weeks<br>* Other names: sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline at Week 24 in proptosis in the study eye | Hertel exophthalmometer is used to measure the prominence of the eye. It measures the anterior projection of the eye from the lateral orbital rim to the cornea (proptosis). | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proptosis