Clinical trial NCT06248619: A Trial to Investigate Teprotumumab Subcutaneous Administration Compared With Placebo in Male and Female Adult Participants With Moderate-to-severe Active Thyroid Eye Disease
Official title: A Phase 3, Randomized, Double-masked, Placebo-controlled, Parallel-group, Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous Teprotumumab in Participants With Moderate-to-Severe Active Thyroid Eye Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Thyroid Eye Disease
Keywords: Teprotumumab
Active Thyroid Eye Disease
Tepezza
Teprotumumab-trbw
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-02-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study consists of a randomized double-masked, placebo-controlled, parallel-group, multicenter trial with an optional open-label treatment period for proptosis non-responders who complete the Double-masked Treatment Period.

Detailed description: The main objective of the study is to evaluate the effect of teprotumumab subcutaneous administration versus placebo on the proptosis responder rate (ie, the percentage of participants with a ≥ 2-mm reduction from Baseline in the study eye without deterioration \[≥ 2-mm increase\] of proptosis in the fellow eye) at Week 24.

Acquired from Horizon in 2024.

Eligibility criteria: Inclusion Criteria:

1. Participant must provide written informed consent.
2. Participant can be male or female and must be between the ages of 18 and 80 years, inclusive, at Screening.
3. Participant must have a clinical diagnosis of Graves' disease associated with active TED with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye at Screening and Baseline.
4. Participant must have moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily life), usually associated with 1 or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement and/or inconstant or constant diplopia. (Note: Participants with no diplopia at Baseline will be limited to approximately 25% of the total number enrolled.)
5. Participant has 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.
6. Participant had onset of active TED symptoms (as determined by participant records) within 15 months prior to Baseline.
7. Participants must be euthyroid with the baseline disease under control or have mild hypoor hyperthyroidism (defined as free thyroxine \[FT4\] and free triiodothyronine \[FT3\] 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.
8. Participant does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial.
9. Women of childbearing potential must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (ie, prior to each dose and throughout participation in the trial).
10. Participant is willing and able to comply with the protocol requirements for the duration of the trial.

Exclusion Criteria:

1. Participant has decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart (or equivalent), new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
2. Participant has corneal decompensation unresponsive to medical management.
3. Participant has a decrease in CAS of ≥ 2 points between Screening and Baseline.
4. Participant has a decrease in proptosis of ≥ 2 mm between Screening and Baseline.
5. Participant had prior orbital irradiation, orbital decompression or strabismus surgery (excluding childhood strabismus surgeries unrelated to TED/Graves' disease).
6. Participant is planning to have eyelid surgery during the trial.
7. Participant received periocular botulinum toxin injection within 12 months prior to Screening.
8. Participant has any systemic use of a steroid (IV or oral) or steroid eye drops for the treatment of TED or other conditions within 3 weeks prior to Screening. Exceptions include local administration (excluding periocular), eg, topical, intra-articular, and inhaled steroids, as well as steroids used to treat infusion reactions.

Primary outcomes:
measure: Proptosis responder rate (percentage of participants with a ≥ 2-mm reduction from baseline in proptosis in the study eye without deterioration [≥ 2-mm increase] of proptosis in the fellow eye).
timeFrame: Week 24
Secondary outcomes:
measure: Mean change from Baseline in proptosis measurement in the study eye
timeFrame: Week 24
measure: Overall responder rate (percentage of participants with ≥ 2-point reduction in CAS AND ≥ 2-mm reduction in proptosis from Baseline, provided there is no corresponding deterioration [≥ 2-point/mm increase] in CAS or proptosis in the fellow eye)
timeFrame: Week 24
measure: Percentage of participants with a CAS value of 0 or 1
timeFrame: Week 24
measure: Change from Baseline in diplopia as ordinal response categories
timeFrame: Week 24
measure: Diplopia responder rate, defined as the percentage of participants with Baseline binocular diplopia > 0 who have a reduction of ≥ 1 grade
timeFrame: Week 24
measure: Complete diplopia responder rate, defined as the percentage of participants with a Baseline binocular diplopia score > 0 and a score of 0
timeFrame: Week 24
measure: Mean change from Baseline in the GO-QoL questionnaire overall score
timeFrame: Week 24
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Catalina Eye Care - NVISION - PPDS
state: Arizona
city: La Jolla
country: United States
facility: Shiley Eye Center University of California at San Diego
state: California
city: Newport Beach
country: United States
facility: Amy Patel Jain MD Inc.
state: California
city: Chicago
country: United States
facility: Chicago Oculofacial Plastic Surgery
state: Illinois
city: Orland Park
country: United States
facility: Advanced Quality Medical Research
state: Illinois
city: Kansas City
country: United States
facility: KU Medical Center, University of Kansas
state: Kansas
city: Weymouth
country: United States
facility: Ophthalmic Consultants of Boston - Weymouth
state: Massachusetts
city: Ann Arbor
country: United States
facility: W Kellogg Eye Center
state: Michigan
city: Henderson
country: United States
facility: Las Vegas Endocrinology
state: Nevada
city: Somerset
country: United States
facility: The Center for Eye and Facial Plastic Surgery
state: New Jersey
city: Portland
country: United States
facility: Casey Eye Institute -515 SW Campus Dr
state: Oregon
city: Erie
country: United States
facility: Erie Retina Research, LLC - 300 State St
state: Pennsylvania
city: Philadelphia
country: United States
facility: Scheie Eye Institute
state: Pennsylvania
city: Memphis
country: United States
facility: University of Tennessee Health Science Center - 848 Adams Ave
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine-1977 Butler Blvd
state: Texas
city: Houston
country: United States
facility: Neuro-Eye Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: Aesthetic Facial and Oculoplastic Surgeons
state: Texas
city: Seattle
country: United States
facility: University of Washington Eye Institute
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Eye Institute
state: West Virginia
city: Lomas de Zamora
country: Argentina
facility: Centro de Ojos Loria
state: Buenos Aires
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Organización Médica de Investigación
state: Ciudad Autónoma De BuenosAires
city: Rosario
country: Argentina
facility: Grupo Laser Visión
state: Santa Fe
city: Sydney
country: Australia
facility: Sydney Eye Hospital
state: New South Wales
city: Wooloongabba
country: Australia
facility: Queensland Eye Institute
state: Queensland
city: Adelaie
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Centre For Eye Research Australia Ltd
state: Victoria
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Research Institute (VCHRI) - 2550 Willow St
state: British Columbia
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre Research Institute
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval CUO Recherche Clinique Hopital du St-Sacrement
city: Marseille
country: France
facility: AP-HM-Hôpital de La Conception
state: Bouches-du-Rhône
city: Lille
country: France
facility: Hôpital Claude Huriez
state: Nord
city: Paris
country: France
facility: Centre Hospitalier National D'ophtalmologie Des Quinze Vingts
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara
city: Fukuoka-Shi
country: Japan
facility: Hayashi Eye Hospital
state: Hukuoka
city: Mito-Shi
country: Japan
facility: Kozawa Eye hospital and Diabetes Center
state: Ibaraki
city: Kanazawa-shi
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Isikawa
city: Miyazaki-Shi
country: Japan
facility: University of Miyazaki Hospital
state: Miyazaki
city: Niigata-Shi
country: Japan
facility: Niigata University Medical and Dental Hospital
state: Niigata
city: Osaka-Shi Yodogawa-Ku
country: Japan
facility: Gokeikai Osaka Kaisei Hospital
state: Ôsaka
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Santiago de Compostela
country: Spain
facility: Hospital Provincial de Conxo
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia-Avda de Fernando Abril Martorell 106
city: Changhua County
country: Taiwan
facility: Changhua Christian Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: