A Study of TEPEZZA® Treatment in Participants With Thyroid Eye Disease

A Phase 1b, Open-label, Multicenter Trial to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Formulations of a Single Subcutaneous Dose of Teprotumumab Followed by Multiple Intravenous Doses of TEPEZZA in Participants With Thyroid Eye Disease

The main goal of this study is to learn how teprotumumab will be processed in the body (Pharmacokinetics) subcutaneously and whether it is safe and tolerable after administration into adult patients with thyroid eye disease.

Study Overview

• Status: Completed
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: Teprotumumab

Detailed Description

This is a Phase 1b, open-label, multicenter trial to assess the PK, safety, and tolerability of a single SC dose of lyophilized teprotumumab and high concentration formulation teprotumumab in participants with thyroid eye disease. Approximately 6 participants (in Cohort 1) and approximately 10 participants (in Cohort 2) who meet the trial eligibility criteria will be enrolled in a 1:1 ratio.

Study acquired from Horizon in 2024.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute - University of Miami
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Barnes Jewish Hospital Washington University
  • Texas
    • Bellaire, Texas, United States, 77401
      • Neuro-Eye Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Thyroid eye disease (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis, and/or inconstant or constant diplopia.
2. Proptosis ≥ 3 mm increase from the participant's baseline (prior to diagnosis of TED), as estimated by treating physician and/or proptosis ≥ 3 mm above normal for race and gender.
3. Participant must be euthyroid with baseline disease under control or have mild hypo- or hyperthyroidism at Screening. 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 trial.
4. Does not require immediate surgical ophthalmological intervention.
5. Participants with diabetes must have HbA1c ≤ 8.0% at Screening.

Exclusion Criteria:

1. Decreased best-corrected visual acuity due to optic neuropathy within the last 6 months.
2. Corneal decompensation unresponsive to medical management in the study eye.
3. Decrease in proptosis of ≥ 2 mm in the study eye between Screening and Baseline.
4. Alanine aminotransferase or aspartate aminotransferase > 3x the upper limit of normal or estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2 at Screening.
5. Use of any steroid (IV, oral, steroid eye drops) for the treatment of TED or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids and steroids used to treat infusion reactions.
6. Any treatment with rituximab, tocilizumab, or any other non-steroid immunosuppressive agent within 90 days prior to the first injection of investigational product on Day 1.
7. Any previous treatment with HZN-001 or TEPEZZA (teprotumumab-trbw), including previous enrollment in this trial or participation in a prior TEPEZZA trial.
8. Treatment with any mAb within 3 months prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive a single dose of lyophilized teprotumumab by subcutaneous (SC) administration on Day 1 followed by intravenous (IV) infusions of teprotumumab at the approved dosing regimen.	Drug: Teprotumumab; SC administration and IV infusion; Other Names: Tepezza
Experimental: Cohort 2; Participants will receive a single high concentration formulation teprotumumab by SC administration on Day 1 followed by IV infusions of teprotumumab at the approved dosing regimen.	Drug: Teprotumumab; SC administration and IV infusion; Other Names: Tepezza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Curve (AUC) of Teprotumumab	AUC will be evaluated from the collected PK samples.	Pre dose through Week 6
PK: Maximum Serum Concentration (Cmax) of Teprotumumab	Cmax will be evaluated from the collected PK samples.	Pre dose through Week 6
Number of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.	Up to Week 6

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2022
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Thyroid Eye Disease; Teprotumumab; TEPEZZA
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Thyroid Diseases
• Other Study ID Numbers: HZNP-TEP-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No