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

Launched by AMGEN · Oct 6, 2020

Keywords

ClinConnect Summary

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 e...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Written informed consent.
• • 2. Male or female at least 18 years old at Screening.
• 3. 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:
• • 1. no progression in proptosis for at least 1 year prior to Screening
• • 2. if participant has history of diplopia due to TED, no progression in diplopia for at least 1 year prior to Screening
• • 3. no new inflammatory TED symptoms for at least 1 year prior to Screening
• • 4. CAS ≤1 at the Screening and Baseline Visits.
• • 5. 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.
• • 6. 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.
• • 7. Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
• • 8. Diabetic participants must have HbA1c ≤8.0% at Screening.
• • 9. 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.
• • 10. 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.
• • 11. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
• Exclusion Criteria:
• • 1. 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.
• • 2. Corneal decompensation unresponsive to medical management in the study eye
• • 3. Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
• • 4. Prior orbital irradiation, orbital decompression in the study eye.
• • 5. Prior strabismus surgery.
• • 6. Alanine aminotransferase or aspartate aminotransferase \>3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73 m2 at Screening.
• • 7. 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.
• • 8. 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.
• • 9. Any previous treatment with TEPEZZA, including previous enrollment in this trial or participation in a prior teprotumumab trial.
• • 10. Treatment with any mAb within 3 months prior to Screening.
• • 11. Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
• • 12. 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.
• • 13. Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
• • 14. Pregnant or lactating women.
• • 15. 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.
• • 16. Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity reactions to mAbs.
• • 17. Poorly controlled human immunodeficiency virus infection or untreated or positive viral load for hepatitis C or hepatitis B infections.
• • 18. Any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.