Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study

This is a multi-center, open-label extension study of HZNP-TEP-301 (NCT03298867) examining
the safety and efficacy of teprotumumab in the treatment of TED in adult participants.
Participants who complete the 24-week double-masked Treatment Period in Study HZNP-TEP-301
and are proptosis non-responders or were proptosis responders at Week 24 but meet the
criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301 will be
eligible for enrollment.

All participants who choose to participate will receive 8 infusions of teprotumumab (10 mg/kg
for the first infusion followed by 20 mg/kg for the remaining 7 infusions) in an open-label
fashion.The Baseline (Day 1) Visit of this extension study will occur within 14 days after
the final visit of Study HZNP-TEP-301 (Week 24 for proptosis non-responders and up to Week 72
for participants who relapse). During the open-label Treatment Period, study drug infusions
are scheduled for Day 1 (Baseline), and Weeks 3, 6, 9, 12, 15, 18, and 21, (with the final
visit at Week 24). After completion of the Treatment Period, subjects who were proptosis
non-responders in Study HZNP-TEP-301 will enter a 24-week Follow-Up Period during which study
drug will not be administered and clinic visits are scheduled for 1, 3, and 6 months (Visits
Month 7, 9, and 12) after the Week 24 visit. Subjects will be contacted 6 and 12 months later
by phone or email to enquire if any treatment for TED had been received since the last study
contact.

Participants who relapse during the Follow-Up Period of HZNP-TEP-301 and choose to enter this
extension study will not participate in the Follow-Up Period of this study but will be
contacted by phone or email 6 and 12 months after the Week 24 visit.

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 ULN (according to age) at the
most recent clinic visit.

- Diabetic participants must have well-controlled disease (defined as HgbA1c < 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.