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

Thyroid-Associated Ophthalmopathy Clinical Trial

Official title:

A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study Of RV 001, An Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (q3W) By Intravenous (IV) Infusion In Patients Suffering From Active Thyroid Eye Disease (TED)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01868997
• Other study ID #: TED01RV
• Secondary ID: FD004792-01A1201
• Status: Completed
• Phase: Phase 2
• First received: May 2, 2013
• Last updated: March 27, 2018
• Start date: July 2013
• Est. completion date: February 22, 2017

Study information

• Verified date: March 2018
• Source: Horizon Pharma USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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"

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: February 22, 2017
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Associated Ophthalmopathies
• Thyroid Diseases
• Thyroid-Associated Ophthalmopathy

Intervention

Drug:
• teprotumumab

• normal saline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Horizon Pharma USA, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Italy,  United Kingdom, 

References & Publications (1)

Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmop — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Responder Status at 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.	Week 24
Secondary	Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])	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).	Baseline to Week 24
Secondary	Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)	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.	Baseline to Week 24
Secondary	Overall Average Change From Baseline in CAS to Week 24 (MMRM)	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.	Baseline to Week 24
Secondary	Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)	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.	Baseline to Week 24
Secondary	Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)	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.	Baseline to Week 24