Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study
Condition: Thyroid Eye Disease
MeSH terms: Eye Diseases; Graves Ophthalmopathy
Intervention: Teprotumumab
Intervention description: 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).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The overall objective is to evaluate the safety and efficacy of teprotumumab in the treatment
      of thyroid eye disease (TED) in participants who participated in the lead-in study
      HZNP-TEP-301 (NCT03298867; OPTIC) and who were either proptosis non-responders at Week 24 of
      HZNP-TEP-301 or were proptosis responders at Week 24 but met the criteria for re-treatment
      due to relapse during the Follow-Up Period of HZNP-TEP-301.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent.

          -  Completed the 24-week double-masked Treatment Period in Study HZNP-TEP-301
             (NCT03298867).

          -  Proptosis non-responder (< 2 mm reduction in proptosis in the study eye) at Week 24 of
             Study HZNP-TEP-301 OR proptosis responder at Week 24 who relapses during the Follow-Up
             Period of Study HZNP-TEP-301.

          -  Participant must be euthyroid with the baseline disease under control, or have mild
             hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine
             [FT3] levels < 50% above or below the normal limits) at the most recent clinic visit.
             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 clinical trial.

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 times the upper
             limit of normal (ULN) or serum creatinine <1.5 times the upper limit of normal (ULN;
             according to age) at the most recent clinic visit.

          -  Diabetic participants must have well-controlled disease (defined as hemoglobin A1C
             [HbA1c] < 9.0% at most recent clinic visit).

          -  Does not require immediate surgical ophthalmological intervention and is not planning
             corrective surgery/irradiation during the course of the study.

          -  Women of childbearing potential must have a negative urine pregnancy test at
             Baseline/Day 1. Participants who are sexually active with a non-vasectomized male
             partner must agree to use 2 reliable forms of contraception during the trial and
             continue for 180 days after the last dose of study drug. One of the 2 forms of
             contraception is recommended to be hormonal, such as an oral contraceptive. Hormonal
             contraception must be in use for at least one full cycle prior to Baseline. Highly
             effective contraceptive methods (with a failure rate less than 1% per year), when used
             consistently and correctly, includes implants, injectables, combined oral
             contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised
             partner.

          -  Male participants must be surgically sterile or, if sexually active with a female
             partner of childbearing potential, must agree to use a barrier contraceptive method
             from Baseline through 180 days after the last dose of study drug.

          -  Participant is willing and able to comply with the prescribed treatment protocol and
             evaluations for the duration of the study.

          -  Has not received any treatment for TED since Week 24 of the of the HZNP-TEP-301 study.

        Exclusion Criteria:

          -  Participants will be ineligible if, in the opinion of the Investigator, they are
             unlikely to comply with the study protocol or have a concomitant disease or condition
             that could interfere with the conduct of the study or potentially put the participant
             at unacceptable risk.

          -  The exclusion criteria (except those related to screening) of protocol
             HZNP-TEP-301(NCT03298867) also apply to this open-label extension study.