NCT03298867

Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study

A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Active Thyroid Eye Disease

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 83 (actual)
• Sponsor: Amgen · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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. Study acquired from Horizon in 2024.

Conditions

• Thyroid Eye Disease
• Graves' Orbitopathy

Interventions

Type	Name	Description
BIOLOGICAL	Teprotumumab	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).
OTHER	Placebo	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).

Timeline

• Start date: 2017-10-04
• Primary completion: 2019-02-13
• Completion: 2020-11-30
• First posted: 2017-10-02
• Last updated: 2024-07-11
• Results posted: 2020-03-10

Locations

14 sites across 3 countries: United States, Germany, Italy

Regulatory

• FDA-regulated drug study