A Study Evaluating TEPEZZA® Treatment in Patients With Chronic (Inactive) Thyroid Eye Disease

NCT04583735 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HZNP-TEP-403
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 12

Brief Summary

The overall objective is to investigate the efficacy, safety and tolerability of TEPEZZA® in participants with chronic (inactive) TED (thyroid eye disease). Approximately 57 participants will be enrolled. There will be a treatment period (through Week 24) and a follow up period (where TEPEZZA will not be infused).

Conditions

Thyroid Eye Disease; Chronic (Inactive) Thyroid Eye Disease

Keywords

Proptosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Proptosis of Study Eye at Week 24

  Proptosis assessments were performed using a Hertel exophthalmometer. It measures the anterior projection of the eye from the lateral orbital rim to the cornea (proptosis).

  Baseline, week 24

Study Arms (2)

TEPEZZA

OTHER

Participants received intravenous infusion of 10 milligrams per kilogram (mg/kg) teprotumumab at first infusion and then 20 mg/kg once every 3 weeks (Q3W) for next 7 infusions during the double masked treatment period. Proptosis non-responders who completed the double-masked treatment period had opted to receive 10 mg/kg teprotumumab at first infusion and then 20 mg/kg Q3W for next 7 infusions during open label treatment period.

Biological: TEPEZZA

Placebo

PLACEBO COMPARATOR

Participants received teprotumumab matching placebo by intravenous infusion, Q3W for 8 infusions during the double masked treatment period. Proptosis non-responders who completed the double-masked treatment period had opted to receive 10 mg/kg teprotumumab at first infusion and then 20 mg/kg Q3W for next 7 infusions during open label treatment period.

Drug: Placebo

Interventions

TEPEZZA BIOLOGICAL

Intravenous infusion

Also known as: teprotumumab-trbw, HZN-001

TEPEZZA

Placebo DRUG

Intravenous infusion

Also known as: sodium chloride

Placebo

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Male or female at least 18 years old at Screening.
• Initial diagnosis of TED ≥2 years but \<10 years prior to Screening. Clinical diagnosis of stable, chronic (inactive) TED, as determined by participant medical records indicating a Clinical Activity Score (CAS) ≤1 in both eyes for at least 1 year prior to Screening or all of the following:
• no progression in proptosis for at least 1 year prior to Screening
• if participant has history of diplopia due to TED, no progression in diplopia for at least 1 year prior to Screening
• no new inflammatory TED symptoms for at least 1 year prior to Screening
• CAS ≤1 at the Screening and Baseline Visits.
• Proptosis ≥3-mm increase from participant's Baseline (prior to diagnosis of TED), as estimated by treating physician and/or proptosis ≥3 mm above normal for race and gender.
• Participants must be euthyroid with the participant's Baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels \<50% above or below the normal limits) 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.
• Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
• Diabetic participants must have HbA1c ≤8.0% at Screening.
• Participants with a history of inflammatory bowel disease, ulcerative colitis or Crohn's disease must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to screening and no planned surgery during the trial. Concomitant stable therapies for inflammatory bowel disease without modifications in the 3 months prior to Screening are allowed.
• Women of childbearing potential (including those with an onset of menopause \<2 years prior to Screening, non-therapy-induced amenorrhea for \<12 months prior to Screening, or not surgically sterile \[absence of ovaries and/or uterus\]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (i.e., prior to each dose and throughout participant's participation); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of trial drug. Highly effective contraceptive methods (failure rate \<1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, sexual abstinence and vasectomized partner.
• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

You may not qualify if:

• Decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
• Corneal decompensation unresponsive to medical management in the study eye
• Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
• Prior orbital irradiation, orbital decompression in the study eye.
• Prior strabismus surgery.
• Alanine aminotransferase or aspartate aminotransferase \>3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73 m2 at Screening.
• 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.
• Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of trial drug or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of trial drug. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of trial drug.
• Any previous treatment with TEPEZZA, including previous enrollment in this trial or participation in a prior teprotumumab trial.
• Treatment with any mAb within 3 months prior to Screening.
• Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
• Use of an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
• Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
• Pregnant or lactating women.
• Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

The Private Practice of Raymond Douglas

Beverly Hills, California, 90210, United States

Location

Perlman Medical Offices / UCSD

La Jolla, California, 92037, United States

Location

MACRO Trials

Los Angeles, California, 90048, United States

Location

Univ of Colorado Dept of Ophthalmology

Aurora, Colorado, 80045, United States

Location

Bascom Palmer Eye Institute / Univ of Miami

Miami, Florida, 33136, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63108, United States

Location

Las Vegas Endocrinology

Las Vegas, Nevada, 89074, United States

Location

Endocrinology Specialists & Thyroid Center

Greenville, South Carolina, 29605, United States

Location

Hamilton Eye Institute / U Tennessee

Memphis, Tennessee, 38163, United States

Location

Neuro-Eye Clinical Trials

Houston, Texas, 77401, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 52336, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Graves Ophthalmopathy; Bronchiolitis Obliterans Syndrome; Sedentary Behavior; Exophthalmos

Interventions

teprotumumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Behavior

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Medical Monitor
• Organization: Horizon Pharma USA, Inc.

medicalinformation@horizontherapeutics.com

1-866-479-6742

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 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 12, 2020
• Study Start: September 2, 2021
• Primary Completion: March 17, 2023
• Study Completion: October 12, 2023
• Last Updated: July 1, 2024
• Results First Posted: April 26, 2024

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 (12)