TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study

NCT05002998 | Completed Phase 4 FDA Drug

• 3 other identifiers: HZNP-TEP-4022020-005999-362024-515090-96-00
• Study Type: interventional
• Target: 313
• Locations: 6 countries
• Sites: 28

Brief Summary

This is a double-masked, randomized, parallel-assignment, multicenter trial examining the safety and tolerability of teprotumumab in the treatment of Thyroid Eye Disease (TED) in adult participants. This international, Phase 3b/4 trial is being conducted to fulfill an FDA post-marketing requirement for a descriptive trial to evaluate the safety, efficacy and need for re-treatment of 3 different teprotumumab treatment durations for TED. In addition, serum samples from participants with a Baseline Clinical Activity Score (CAS) ≥3 will be evaluated for biomarkers of disease.

Conditions

Thyroid Eye Disease

Keywords

TED

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants who experience at least 1 treatment-emergent adverse event (TEAE) and the percentage of participants who experience at least 1 treatment emergent AESI during treatment with teprotumumab

  Treatment emergent adverse events and treatment emergent adverse events of special interest will be evaluated from the beginning of the study until follow up.

  Screening to End of Study (last visit possible is Week 136)

• Percentage of Participants who receive re-treatment

  Participants who are not proptosis responders after initial treatment or participants who are proptosis responders after initial treatment but who have flared during follow-up (relapsed).

  Week 27 to Week 136

Study Arms (3)

Teprotumumab 4 Infusions

OTHER

• 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of: * Placebo if a participant is a treatment responder at Week 12 or * Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12

Drug: Teprotumumab; Drug: Placebo

Teprotumumab 8 Infusions

OTHER

8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)

Drug: Teprotumumab

Teprotumumab 16 Infusions

OTHER

16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)

Drug: Teprotumumab

Interventions

Teprotumumab DRUG

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 containing, in addition to the drug substance, 20 mmol/L histidine-histidine chloride, 250 mmol/L trehalose and 0.01% polysorbate 20 (w/w). Prior to administration, each vial containing 500 mg teprotumumab freeze-dried powder will be reconstituted with 10 mL of sterile water for injection. The resulting solution will have a concentration of 47.6 mg/mL teprotumumab-trbw antibody. The reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration

Also known as: TEPEZZA

Teprotumumab 16 Infusions; Teprotumumab 4 Infusions; Teprotumumab 8 Infusions

Placebo DRUG

Placebo will consist of a normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as appropriate, per weight-based dosing volumes.

Also known as: Saline Solution

Teprotumumab 4 Infusions

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.
• Male or female between the ages of 18 and 80 years, inclusive, at Screening.
• Initial diagnosis of TED within 7 years prior to Screening.
• Proptosis ≥3 mm from 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 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 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 IBD (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 IBD 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 the participant's participation in the Follow-up Period); 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 teprotumumab. Highly effective contraceptive methods (with a failure rate \<1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, tubal ligation, sexual abstinence or 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, as 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.
• Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
• Prior orbital irradiation, orbital decompression or strabismus surgery.
• Planned eyelid surgery during the course of the trial.
• Alanine aminotransferase or aspartate aminotransferase \>3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73m2 at Screening.
• Use of any steroid (intravenous \[IV\], 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, as well as steroids used to treat infusion reactions.
• Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of teprotumumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.
• Any previous treatment with teprotumumab, 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 5 years (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 (28)

The Private Practice of Raymond Douglas, MD - Beverly Hills

Beverly Hills, California, 90210-5192, United States

Location

USC Roski Eye Institute - Los Angeles

Los Angeles, California, 90033, United States

Location

Stanford University

Palo Alto, California, 94303-3216, United States

Location

University of Colorado - Eye Center - PPDS

Aurora, Colorado, 80045-2517, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136-1119, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905-0001, United States

Location

Casey Eye Institute - OHSU

Portland, Oregon, 97239-3130, United States

Location

Hopital Jean Minjoz

Besançon, Doubs, 25030, France

Location

Hospices Civils de Lyon - Hôpital Louis Pradel

Bron, Rhône, 69677, France

Location

Hôpital Claude Huriez-Lille-Rue Michel Polonovski

Lille, 59000, France

Location

Centre Hospitalier National D'ophtalmologie Des Quinze Vingts

Paris, 75571, France

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

University Medicine Göttingen Germany

Göttingen, Lower Saxony, 37075, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Azienda Ospedaliera Universitaria Federico II

Naples, Campania, 80131, Italy

Location

ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi

Varese, Lombardy, 21100, Italy

Location

ARNAS Garibaldi - PO Garibaldi-Centro

Catania, Sicily, 95124, Italy

Location

Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara

Pisa, Tuscany, 56126, Italy

Location

Hospital La Arruzafa

Córdoba, Córdoba, 14012, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Moorfields Eye Hospital - PPDS

London, London, City of, EC1V 2PD, United Kingdom

Location

Imperial College Healthcare NHS Trust - PPDS

London, London, City of, W21 1NY, United Kingdom

Location

University Hospital of Cardiff

Cardiff, South Glamorgan, CF11 0SN, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 9YD, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website
• Related Info

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

teprotumumab; Saline Solution

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-masked except for the pharmacy staff.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of: * Placebo if a participant is a treatment responder at Week 12 or * Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12 * 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2) * 16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 12, 2021
• Study Start: September 16, 2021
• Primary Completion: December 19, 2025
• Study Completion: December 19, 2025
• Last Updated: January 15, 2026

Record last verified: 2026-01

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

IT (4); US (7); GB (5); FR (4); ES (3); DE (5)