Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study
Condition: Thyroid Eye Disease; Graves' Orbitopathy
MeSH terms: Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      The overall objective is to investigate the efficacy, tolerability, and safety of
      teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the insulin-like growth
      factor-1 receptor [IGF-1R]) administered once every 3 weeks (q3W) for 21 weeks with a final
      assessment at Week 24, in comparison to placebo, in the treatment of participants with
      moderate-to-severe active thyroid eye disease (TED).
    

Detailed description: 
      This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study.
      Approximately 76 participants (38/group) who meet the study eligibility criteria will be
      randomized on Day 1 in a 1:1 ratio (stratified by tobacco use status) to receive 8 infusions
      of teprotumumab or placebo q3W. All participants will enter a 24-week double-masked Treatment
      Period, during which study 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). All study drug dosing will be performed at
      the clinic under the supervision of clinic staff. On each dosing day, scheduled assessments
      (except for adverse event [AE] and concomitant medication use monitoring, which will be
      monitored throughout the clinic visit) will be completed prior to study drug dosing.

      At the end of the double-masked Treatment Period (Week 24), participants who are proptosis
      non-responders (study eye has < 2 mm decrease in proptosis) will be eligible to enter an
      open-label extension study in which participants receive 8 infusions of teprotumumab in an
      open-label fashion.

      At Week 24, proptosis responders, as well as non-responders who choose not to enroll in the
      open-label extension study, will enter a 48-week Follow-Up Period, during which study drug
      will not be administered and clinic visits are scheduled for Weeks 28, 36, 48, 60, and 72.
      Participants who are considered responders at Week 24 but who meet criteria for re-treatment
      due to relapse during the Follow-Up Period may enroll in the open-label extension study.

      Participants who complete the Week 72 Visit will be contacted 6 and 12 months later via phone
      or email by research staff to enquire if any treatment for TED has been received since last
      study contact.
    

Intervention name(s): Teprotumumab; Placebo
Intervention type(s): Biological; Other
Intervention description(s): Teprotumumab is a fully human anti-IGF-1R mAb. Teprotumumab will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of teprotumumab must be reconstituted with 10 mL of water for injection. Reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. Teprotumumab 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).; Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).
Other intervention name(s): HZN-001; Saline solution
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Proptosis; Human monoclonal antibody; insulin-like growth factor-1 receptor; Thyroid-Associated Ophthalmopathy; Autoimmune Thyroid Disease; Graves' Orbitopathy