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A Trial to Investigate Teprotumumab Subcutaneous Administration Compared With Placebo in Male and Female Adult Participants With Moderate-to-severe Active Thyroid Eye Disease

Phase 3
Recruiting
Conditions
Thyroid Eye Disease
Interventions
Registration Number
NCT06248619
Lead Sponsor
Amgen
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo for teprotumumab administered SC
TeprotumumabTeprotumumabTeprotumumab administered SC
Primary Outcome Measures
NameTimeMethod
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).Week 24
Secondary Outcome Measures
NameTimeMethod
Mean change from Baseline in proptosis measurement in the study eyeWeek 24
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)Week 24
Percentage of participants with a CAS value of 0 or 1Week 24
Change from Baseline in diplopia as ordinal response categoriesWeek 24
Diplopia responder rate, defined as the percentage of participants with Baseline binocular diplopia > 0 who have a reduction of ≥ 1 gradeWeek 24
Complete diplopia responder rate, defined as the percentage of participants with a Baseline binocular diplopia score > 0 and a score of 0Week 24
Mean change from Baseline in the GO-QoL questionnaire overall scoreWeek 24

Trial Locations

Locations (52)

Catalina Eye Care - NVISION - PPDS

🇺🇸

Tucson, Arizona, United States

Shiley Eye Center University of California at San Diego

🇺🇸

La Jolla, California, United States

Amy Patel Jain MD Inc.

🇺🇸

Newport Beach, California, United States

Advanced Quality Medical Research

🇺🇸

Orland Park, Illinois, United States

KU Medical Center, University of Kansas

🇺🇸

Kansas City, Kansas, United States

Ophthalmic Consultants of Boston - Weymouth

🇺🇸

Weymouth, Massachusetts, United States

W Kellogg Eye Center

🇺🇸

Ann Arbor, Michigan, United States

Las Vegas Endocrinology

🇺🇸

Henderson, Nevada, United States

The Center for Eye and Facial Plastic Surgery

🇺🇸

Somerset, New Jersey, United States

Casey Eye Institute -515 SW Campus Dr

🇺🇸

Portland, Oregon, United States

Erie Retina Research, LLC - 300 State St

🇺🇸

Erie, Pennsylvania, United States

Scheie Eye Institute

🇺🇸

Philadelphia, Pennsylvania, United States

University of Tennessee Health Science Center - 848 Adams Ave

🇺🇸

Memphis, Tennessee, United States

Baylor College of Medicine-1977 Butler Blvd

🇺🇸

Houston, Texas, United States

Neuro-Eye Clinical Trials

🇺🇸

Houston, Texas, United States

Aesthetic Facial and Oculoplastic Surgeons

🇺🇸

San Antonio, Texas, United States

University of Washington Eye Institute

🇺🇸

Seattle, Washington, United States

West Virginia University Eye Institute

🇺🇸

Morgantown, West Virginia, United States

Centro de Ojos Loria

🇦🇷

Lomas de Zamora, Buenos Aires, Argentina

Hospital Universitario Austral

🇦🇷

Pilar, Buenos Aires, Argentina

Organización Médica de Investigación

🇦🇷

Ciudad Autónoma de Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina

Grupo Laser Visión

🇦🇷

Rosario, Santa Fe, Argentina

Sydney Eye Hospital

🇦🇺

Sydney, New South Wales, Australia

Queensland Eye Institute

🇦🇺

Wooloongabba, Queensland, Australia

Royal Adelaide Hospital

🇦🇺

Adelaie, South Australia, Australia

Centre For Eye Research Australia Ltd

🇦🇺

East Melbourne, Victoria, Australia

Vancouver Coastal Health Research Institute (VCHRI) - 2550 Willow St

🇨🇦

Vancouver, British Columbia, Canada

McGill University Health Centre Research Institute

🇨🇦

Montreal, Quebec, Canada

CHU de Quebec-Universite Laval CUO Recherche Clinique Hopital du St-Sacrement

🇨🇦

Quebec, Canada

AP-HM-Hôpital de La Conception

🇫🇷

Marseille, Bouches-du-Rhône, France

Hôpital Claude Huriez

🇫🇷

Lille, Nord, France

Centre Hospitalier National D'ophtalmologie Des Quinze Vingts

🇫🇷

Paris, France

Universitätsklinikum Tübingen

🇩🇪

Tübingen, Baden-Württemberg, Germany

Universitätsklinikum Essen

🇩🇪

Essen, Nordrhein-Westfalen, Germany

Azienda Ospedaliera Universitaria Federico II

🇮🇹

Napoli, Campania, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Lombardia, Italy

Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello

🇮🇹

Pisa, Italy

Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara

🇮🇹

Pisa, Italy

Hayashi Eye Hospital

🇯🇵

Fukuoka-Shi, Hukuoka, Japan

Kozawa Eye hospital and Diabetes Center

🇯🇵

Mito-Shi, Ibaraki, Japan

Ishikawa Prefectural Central Hospital

🇯🇵

Kanazawa-shi, Isikawa, Japan

University of Miyazaki Hospital

🇯🇵

Miyazaki-Shi, Miyazaki, Japan

Niigata University Medical and Dental Hospital

🇯🇵

Niigata-Shi, Niigata, Japan

Gokeikai Osaka Kaisei Hospital

🇯🇵

Osaka-Shi Yodogawa-Ku, Ôsaka, Japan

Hospital Universitario Virgen de Las Nieves

🇪🇸

Granada, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Provincial de Conxo

🇪🇸

Santiago de Compostela, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Hospital Universitari i Politecnic La Fe de Valencia-Avda de Fernando Abril Martorell 106

🇪🇸

Valencia, Spain

Changhua Christian Hospital

🇨🇳

Changhua County, Taiwan

Chung Shan Medical University Hospital

🇨🇳

Taichung, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

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