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.
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.