Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease

Phase 2

Completed

Conditions: Thyroid Associated Ophthalmopathies
Thyroid-Associated Ophthalmopathy

Interventions: Drug: normal saline
Drug: teprotumumab

Registration Number: NCT01868997

Lead Sponsor: Amgen

Brief Summary: The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED.

"Funding Source - FDA OOPD"

Detailed Description: Study with completed results acquired from Horizon in 2024.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 88

Inclusion Criteria

Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
Fewer than 9 months from onset of TED
No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
Euthyroid or with mild hypo or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits (every effort should be made to correct the mild hypo- or hyperthyroidism promptly)

Exclusion Criteria

Optic neuropathy
Corneal decompensation unresponsive to medical management
Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
Poorly controlled diabetes
Platelets < 100 x 10^9/L
Hemoglobin concentration > 2 g/dL below the lower limit of normal

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	normal saline	A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
Teprotumumab	teprotumumab	Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants start treatment at a dose of 10 mg/kg. At Week 3, the dose is escalated to 20 mg/kg and kept constant for the remainder of the study.

Primary Outcome Measures

Name	Time	Method
Responder Status at Week 24	Week 24	Number of participants classified as responders and non-responders at Week 24. Responders were defined as participants with a reduction in clinical activity score (CAS, see Outcome Measure 4 description for details) of ≥ 2 points, and a reduction in proptosis (amount of protrusion of the eye from the orbital rim) of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye. Participants who had no assessment at 24 weeks were considered non-responders.

Secondary Outcome Measures

Name	Time	Method
Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])	Baseline to Week 24	The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of thyroid eye disorder (TED) by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. The transformed overall score is the sum of scores from all 16 questions to a scale of 0 (worst health) to 100 (best health).
Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)	Baseline to Week 24	The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Visual Functioning score is the sum of scores from following 8 questions to a scale of 0 (worst health) to 100 (best health): bicycling, driving, moving around the house, walking outdoors, reading, watching television (TV), hobby or pastime, feel hindered.
Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)	Baseline to Week 24	Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements were recorded using the Hertel exophthalmometer. Participants with a decrease ≥ 2 mm were considered improving, those with an increase or decrease \< 2 mm were considered remaining stable, and those with an increase ≥ 2 mm were considered worsening.
Overall Average Change From Baseline in CAS to Week 24 (MMRM)	Baseline to Week 24	The 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amended CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling that is considered to be due to active (inflammatory phase) Graves' ophthalmopathy (GO), eyelid erythema, conjunctival redness that is considered to be due to active (inflammatory phase) GO, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity.
Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)	Baseline to Week 24	The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Appearance score is the sum of scores from the following 8 questions to a scale of 0 (worst health) to 100 (best health): feel appearance has changed, feel being stared at, feel people react unpleasantly, influence on self-confidence, feel socially isolated, influence on making friends, appear less often on photos, try to mask changes in appearance.

Trial Locations

Locations (15): Jules Stein Eye Institute at UCLA
🇺🇸
Los Angeles, California, United States
Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
🇮🇹
Milan, Italy
University of Pisa, Azienda Ospedaliera
🇮🇹
Pisa, Italy
Kellogg Eye Center at University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
University of Denver
🇺🇸
Aurora, Colorado, United States
Emory University Department of Ophthalmology
🇺🇸
Atlanta, Georgia, United States
University of Nebraska Medical Center Department of Ophthalmology
🇺🇸
Omaha, Nebraska, United States
Hamilton Eye Institute at University of Tennessee
🇺🇸
Memphis, Tennessee, United States
Casey Eye Institute at Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
University of Iowa Hospitals and Clinics, Department of Ophthalmology
🇺🇸
Iowa City, Iowa, United States
Eye Wellness Center
🇺🇸
Houston, Texas, United States
Medical College of Wisconsin, The Eye Institute
🇺🇸
Milwaukee, Wisconsin, United States
Moorfields Eye Hospital
🇬🇧
London, United Kingdom
Johannes Gutenberg University Medical Center
🇩🇪
Mainz, Germany
Washington University Department of Ophthalmology
🇺🇸
Saint Louis, Missouri, United States