Clinical trial NCT05002998: TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study
Official title: A Phase 3b/4, Double-masked, Randomized, International, Parallel-assignment, Multicenter Trial in Patients With Thyroid Eye Disease to Evaluate the Safety and Tolerability of Different Dosing Durations of Teprotumumab
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Thyroid Eye Disease
Keywords: TED
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-08-12
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * 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)
Primary purpose: TREATMENT

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.

Detailed description: Participants will be screened for eligibility within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio in a double-masked fashion (stratified by CAS(clinical activity score) \[≥3 (active) or \<3 (inactive)\] and disease severity \[severe disease, defined as both proptosis above normal for race and gender with binocular diplopia at Baseline vs. non-severe disease\]) to receive:

* 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 participants 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)

Three weeks following the final infusion of the Initial Treatment Period, there will be a comprehensive End-of-Initial Treatment Visit at Week 24 (Cohorts 1 and 2)/Week 48 (Cohort 3). At this visit, all participants will be assessed for treatment response.

Proptosis responders in all cohorts and non-responders in Cohorts 1 and 2 who choose not to receive a second treatment course, will enter a 52 week Initial Follow-up Period.

Proptosis non-responders in Cohorts 1 and 2 who choose to receive a second treatment course (8 infusions) of teprotumumab will receive an infusion q3W.

Proptosis non-responders in Cohort 3 are not eligible for a second treatment course following initial treatment.

Participants in any of the 3 cohorts who are proptosis responders following the Initial Treatment Period and who flare during the Initial Follow up Period will be eligible to receive re treatment.

Acquired from Horizon in 2024

Eligibility criteria: Inclusion Criteria:

1. Written informed consent.
2. Male or female between the ages of 18 and 80 years, inclusive, at Screening.
3. Initial diagnosis of TED within 7 years prior to Screening.
4. 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.
5. 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.
6. Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
7. Diabetic participants must have HbA1c ≤8.0% at Screening.
8. Participants with a history of IBD (ulcerative colitis or Crohn's disease)

Primary outcomes:
measure: 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
timeFrame: Screening to End of Study (last visit possible is Week 136)
measure: Percentage of Participants who receive re-treatment
timeFrame: Week 27 to Week 136
Secondary outcomes:
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: The Private Practice of Raymond Douglas, MD - Beverly Hills
state: California
city: Los Angeles
country: United States
facility: USC Roski Eye Institute - Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado - Eye Center - PPDS
state: Colorado
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Portland
country: United States
facility: Casey Eye Institute - OHSU
state: Oregon
city: Besançon
country: France
facility: Hopital Jean Minjoz
state: Doubs
city: Bron
country: France
facility: Hospices Civils de Lyon - Hôpital Louis Pradel
state: Rhône
city: Lille
country: France
facility: Hôpital Claude Huriez-Lille-Rue Michel Polonovski
city: Paris
country: France
facility: Centre Hospitalier National D'ophtalmologie Des Quinze Vingts
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Göttingen
country: Germany
facility: University Medicine Göttingen Germany
state: Niedersachsen
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
state: Rheinland-Pfalz
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Varese
country: Italy
facility: ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi
state: Lombardia
city: Catania
country: Italy
facility: ARNAS Garibaldi - PO Garibaldi-Centro
state: Sicilia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara
state: Toscana
city: Cordoba
country: Spain
facility: Hospital La Arruzafa
state: Córdoba
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
state: London, City Of
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: London, City Of
city: Cardiff
country: United Kingdom
facility: University Hospital of Cardiff
state: South Glamorgan
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: Tyne And Wear
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: