Back to resultsTeprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
Primary Purpose
Thyroid Associated Ophthalmopathies, Thyroid-Associated Ophthalmopathy
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
teprotumumab
normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Thyroid Associated Ophthalmopathies focused on measuring Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated, Ophthalmopathy
Eligibility 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 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
Sites / Locations
- Jules Stein Eye Institute at UCLA
- University of Denver
- Emory University Department of Ophthalmology
- University of Iowa Hospitals and Clinics, Department of Ophthalmology
- Kellogg Eye Center at University of Michigan
- Washington University Department of Ophthalmology
- University of Nebraska Medical Center Department of Ophthalmology
- Casey Eye Institute at Oregon Health and Science University
- Hamilton Eye Institute at University of Tennessee
- Eye Wellness Center
- Medical College of Wisconsin, The Eye Institute
- Johannes Gutenberg University Medical Center
- Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
- University of Pisa, Azienda Ospedaliera
- Moorfields Eye Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Teprotumumab
Arm Description
A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01868997
Brief Title
Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
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 Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
July 2013 (Actual)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
February 22, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Horizon Pharma USA, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. 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"
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Associated Ophthalmopathies, Thyroid-Associated Ophthalmopathy
Keywords
Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated, Ophthalmopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
Arm Title
Teprotumumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
teprotumumab
Other Intervention Name(s)
RV 001, HZN-001
Intervention Type
Drug
Intervention Name(s)
normal saline
Primary Outcome Measure Information:
Title
Responder Status at Week 24
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])
Description
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).
Time Frame
Baseline to Week 24
Title
Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)
Description
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.
Time Frame
Baseline to Week 24
Title
Overall Average Change From Baseline in CAS to Week 24 (MMRM)
Description
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.
Time Frame
Baseline to Week 24
Title
Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)
Description
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.
Time Frame
Baseline to Week 24
Title
Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)
Description
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.
Time Frame
Baseline to Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raymond S Douglas, MD, PhD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jules Stein Eye Institute at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Emory University Department of Ophthalmology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa Hospitals and Clinics, Department of Ophthalmology
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Kellogg Eye Center at University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Washington University Department of Ophthalmology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center Department of Ophthalmology
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Casey Eye Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Hamilton Eye Institute at University of Tennessee
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
Eye Wellness Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77005
Country
United States
Facility Name
Medical College of Wisconsin, The Eye Institute
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Johannes Gutenberg University Medical Center
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
University of Pisa, Azienda Ospedaliera
City
Pisa
ZIP/Postal Code
56100
Country
Italy
Facility Name
Moorfields Eye Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
28467880
Citation
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 Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.
Results Reference
result
PubMed Identifier
33768488
Citation
Xin Y, Xu F, Gao Y, Bhatt N, Chamberlain J, Sile S, Hammel S, Holt RJ, Ramanathan S. Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease. Clin Pharmacokinet. 2021 Aug;60(8):1029-1040. doi: 10.1007/s40262-021-01003-3. Epub 2021 Mar 26.
Results Reference
derived
PubMed Identifier
24651704
Citation
Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014 Mar 20;55(3):1735-48. doi: 10.1167/iovs.14-14002.
Results Reference
derived
Learn more about this trial
Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
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