TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study

This is a double-masked, randomized, parallel-assignment, multicenter trial examining the safety and tolerability of teprotumumab in the treatment of Thyroid Eye Disease (TED) in adult participants. This international, Phase 3b/4 trial is being conducted to fulfill an FDA post-marketing requirement for a descriptive trial to evaluate the safety, efficacy and need for re-treatment of 3 different teprotumumab treatment durations for TED. In addition, serum samples from participants with a Baseline Clinical Activity Score (CAS) ≥3 will be evaluated for biomarkers of disease.

Participants will be screened for eligibility within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio in a double-masked fashion (stratified by CAS(clinical activity score) \[≥3 (active) or \<3 (inactive)\] and disease severity \[severe disease, defined as both proptosis above normal for race and gender with binocular diplopia at Baseline vs. non-severe disease\]) to receive:

* 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of:

  * Placebo if a participants is a treatment responder at Week 12 or
  * Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12
* 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)
* 16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)

Three weeks following the final infusion of the Initial Treatment Period, there will be a comprehensive End-of-Initial Treatment Visit at Week 24 (Cohorts 1 and 2)/Week 48 (Cohort 3). At this visit, all participants will be assessed for treatment response.

Proptosis responders in all cohorts and non-responders in Cohorts 1 and 2 who choose not to receive a second treatment course, will enter a 52 week Initial Follow-up Period.

Proptosis non-responders in Cohorts 1 and 2 who choose to receive a second treatment course (8 infusions) of teprotumumab will receive an infusion q3W.

Proptosis non-responders in Cohort 3 are not eligible for a second treatment course following initial treatment.

Participants in any of the 3 cohorts who are proptosis responders following the Initial Treatment Period and who flare during the Initial Follow up Period will be eligible to receive re treatment.

Acquired from Horizon in 2024

Eligibility Criteria:
Inclusion Criteria:

1. Written informed consent.
2. Male or female between the ages of 18 and 80 years, inclusive, at Screening.
3. Initial diagnosis of TED within 7 years prior to Screening.
4. Proptosis ≥3 mm from baseline (prior to diagnosis of TED), as estimated by treating physician, and/or proptosis \>3 mm above normal for race and gender.
5. Participants must be euthyroid with the 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 duration of the trial.
6. Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
7. Diabetic participants must have HbA1c ≤8.0% at Screening.
8. Participants with a history of IBD (ulcerative colitis or Crohn's disease)