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Teprotumumab Treatment in Patients With Active Thyroid Eye Disease

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ClinicalTrials.gov Identifier: NCT01868997
Recruitment Status : Completed
First Posted : June 5, 2013
Results First Posted : August 30, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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"


Condition or disease Intervention/treatment Phase
Thyroid Associated Ophthalmopathies Thyroid-Associated Ophthalmopathy Drug: teprotumumab Drug: normal saline Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Study Start Date : July 2013
Primary Completion Date : March 2016
Study Completion Date : February 21, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Thyroid
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Placebo Comparator: Placebo
A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
Drug: normal saline
Experimental: 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.
Drug: teprotumumab
Other Names:
  • RV 001
  • HZN-001


Outcome Measures

Primary Outcome Measures :
  1. Responder Status at Week 24 [ Time Frame: 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 6 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 :
  1. Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM]) [ Time Frame: 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).

  2. Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM) [ Time Frame: 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.

  3. Change From Baseline in CAS to Week 24 (MMRM) [ Time Frame: 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.

  4. Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM) [ Time Frame: 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 TV, hobby or pastime, feel hindered.

  5. Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM) [ Time Frame: 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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01868997


Locations
United States, California
Jules Stein Eye Institute at UCLA
Los Angeles, California, United States, 90095
United States, Colorado
University of Denver
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University Department of Ophthalmology
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Hospitals and Clinics, Department of Ophthalmology
Iowa City, Iowa, United States, 52242
United States, Michigan
Kellogg Eye Center at University of Michigan
Ann Arbor, Michigan, United States, 48105
United States, Missouri
Washington University Department of Ophthalmology
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center Department of Ophthalmology
Omaha, Nebraska, United States, 68198
United States, Oregon
Casey Eye Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Tennessee
Hamilton Eye Institute at University of Tennessee
Memphis, Tennessee, United States, 38163
United States, Texas
Eye Wellness Center
Houston, Texas, United States, 77005
United States, Wisconsin
Medical College of Wisconsin, The Eye Institute
Milwaukee, Wisconsin, United States, 53226
Germany
Johannes Gutenberg University Medical Center
Mainz, Germany, 55101
Italy
Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
Milan, Italy, 20122
University of Pisa, Azienda Ospedaliera
Pisa, Italy, 56100
United Kingdom
Moorfields Eye Hospital
London, United Kingdom
Sponsors and Collaborators
Horizon Pharma USA, Inc.
Investigators
Principal Investigator: Raymond S Douglas, MD,PhD Cedars-Sinai Medical Center
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT01868997     History of Changes
Other Study ID Numbers: TED01RV
FD004792-01A1 ( Other Identifier: FDA - Office of Orphan Product Development )
2014-000113-31 ( EudraCT Number )
First Posted: June 5, 2013    Key Record Dates
Results First Posted: August 30, 2017
Last Update Posted: August 30, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Horizon Pharma USA, Inc.:
Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated
Ophthalmopathy

Additional relevant MeSH terms:
Thyroid Diseases
Eye Diseases
Graves Ophthalmopathy
Endocrine System Diseases
Eye Diseases, Hereditary
Graves Disease
Orbital Diseases
Autoimmune Diseases
Immune System Diseases
Exophthalmos
Goiter
Hyperthyroidism