Clinical trial NCT03461211: Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study
Official title: Multicenter, Safety and Efficacy, Open-Label Extension Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Thyroid Eye Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thyroid Eye Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-03-09
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 are 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.

Study acquired from Horizon in 2024.

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.

Primary outcomes:
measure: Percentage of Participants With a ≥ 2 mm Reduction From Baseline in the Study Eye Without Deterioration of Proptosis in the Fellow Eye at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants With a European Group on Graves' Ophthalmopathy (EUGOGO) Amended Clinical Activity Score (CAS) Total Score of 0 or 1 in the Study Eye at Week 24
timeFrame: Week 24
measure: Change in Proptosis From Baseline to Week 24
timeFrame: Study Baseline, Week 24
measure: Percentage of Participants Who Were Diplopia Responders at Week 24
timeFrame: Week 24
measure: Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score
timeFrame: Study Baseline, Week 24
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Macro, Llc
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Ann Arbor
country: United States
facility: Kellogg Eye Center at University of Michigan
state: Michigan
city: Portland
country: United States
facility: Casey Eye Institute at Oregon Health and Science
state: Oregon
city: Memphis
country: United States
facility: Hamilton Eye Institute at University of Tennessee Health
state: Tennessee
city: Houston
country: United States
facility: Eye Wellness Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, The Eye Institute
state: Wisconsin
city: Essen
country: Germany
facility: University Hospital Essen, Department of Ophthalmology
city: Mainz
country: Germany
facility: Johannes Gutenberg University Medical Center
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore
city: Pisa
country: Italy
facility: University of Pisa, Department of Clinical and Experimental Medicine
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Xin Y, Xu F, Gao Y, Bhatt N, Chamberlain J, Sile S, Hammel S, Holt RJ, Ramanathan S. Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease. Clin Pharmacokinet. 2021 Aug;60(8):1029-1040. doi: 10.1007/s40262-021-01003-3. Epub 2021 Mar 26.