| Eligibility |
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.
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