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

NCT03461211 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: HZNP-TEP-3022017-002713-58
• Study Type: interventional
• Target: 51
• Locations: 3 countries
• Sites: 13

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.

Conditions

Thyroid Eye Disease

Outcome Measures

Primary Outcomes (1)

• 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

  Proptosis responders were defined as participants with a ≥ 2 mm reduction from study baseline in proptosis in the study eye, without deterioration (≥ 2 mm increase) of proptosis in the fellow eye at Week 24. Participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic.

  Baseline, Week 24

Secondary Outcomes (4)

• 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

  Week 24

• Change in Proptosis From Baseline to Week 24

  Study Baseline, Week 24

• Percentage of Participants Who Were Diplopia Responders at Week 24

  Week 24

• Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score

  Study Baseline, Week 24

Study Arms (1)

Teprotumumab

EXPERIMENTAL

Eight infusions of teprotumumab every 3 weeks (q3W) for a total of 21 weeks: teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.

Biological: Teprotumumab

Interventions

Teprotumumab BIOLOGICAL

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).

Also known as: HZN-001

Teprotumumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (13)

Macro, Llc

Beverly Hills, California, 90212, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90078, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33135, United States

Location

Kellogg Eye Center at University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Casey Eye Institute at Oregon Health and Science

Portland, Oregon, 97239, United States

Location

Hamilton Eye Institute at University of Tennessee Health

Memphis, Tennessee, 38163, United States

Location

Eye Wellness Center

Houston, Texas, 77005, United States

Location

Medical College of Wisconsin, The Eye Institute

Milwaukee, Wisconsin, 53226, United States

Location

University Hospital Essen, Department of Ophthalmology

Essen, 45147, Germany

Location

Johannes Gutenberg University Medical Center

Mainz, 55131, Germany

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore

Milan, 20122, Italy

Location

University of Pisa, Department of Clinical and Experimental Medicine

Pisa, 56100, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

Related Publications (1)

• 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.

  PMID: 33768488 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

teprotumumab

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Roxann Becco
• Organization: Horizon Pharma USA, Inc.

clinicaltrials@horizontherapeutics.com

866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: March 9, 2018
• Study Start: April 16, 2018
• Primary Completion: June 8, 2020
• Study Completion: February 17, 2021
• Last Updated: June 28, 2024
• Results First Posted: July 19, 2021

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (8); IT (3); DE (2)