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| ID | Type | Description | Link |
|---|---|---|---|
| FD004792-01A1 | Other Identifier | FDA - Office of Orphan Product Development (OOPD) | |
| 2014-000113-31 | EudraCT Number |
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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"
Study with completed results acquired from Horizon in 2024.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. |
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| Teprotumumab | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| teprotumumab | Drug |
|
| |
| normal saline |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jules Stein Eye Institute at UCLA | Los Angeles | California | 90095 | United States | ||
| University of Denver |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28467880 | Result | 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. | |
| 33768488 |
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A total of 88 participants were enrolled (all participants who signed informed consent were considered enrolled in this study); 1 participant was never dosed and early terminated.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | A placebo infusion (normal saline) was administered once every 3 weeks (q3W) by intravenous (IV) infusion over a period of 24 weeks for a total of 8 infusions. |
| FG001 | Teprotumumab |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Drug |
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| Baseline to Week 24 |
| 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 |
| 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 |
| 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 |
| 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 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Emory University Department of Ophthalmology | Atlanta | Georgia | 30322 | United States |
| University of Iowa Hospitals and Clinics, Department of Ophthalmology | Iowa City | Iowa | 52242 | United States |
| Kellogg Eye Center at University of Michigan | Ann Arbor | Michigan | 48105 | United States |
| Washington University Department of Ophthalmology | St Louis | Missouri | 63110 | United States |
| University of Nebraska Medical Center Department of Ophthalmology | Omaha | Nebraska | 68198 | United States |
| Casey Eye Institute at Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Hamilton Eye Institute at University of Tennessee | Memphis | Tennessee | 38163 | United States |
| Eye Wellness Center | Houston | Texas | 77005 | United States |
| Medical College of Wisconsin, The Eye Institute | Milwaukee | Wisconsin | 53226 | United States |
| Johannes Gutenberg University Medical Center | Mainz | 55101 | Germany |
| Fondazione Ca' Granda Ospedale Policlinico Graves GO Center | Milan | 20122 | Italy |
| University of Pisa, Azienda Ospedaliera | Pisa | 56100 | Italy |
| Moorfields Eye Hospital | London | United Kingdom |
| 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. |
| 24651704 | Derived | 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. |
Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. |
| BG001 | Teprotumumab | Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). | Posted | Count of Participants | Participants | Week 24 |
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| 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). | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 24 |
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| 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. | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment. | Posted | Least Squares Mean | Standard Error | mm | Baseline to Week 24 |
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| 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. | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 24 |
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| 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. | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 24 |
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| 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. | Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline to Week 24 |
|
Up to Week 72
Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Safety Population: Placebo | A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received. | 0 | 44 | 1 | 44 | 21 | 44 |
| EG001 | Safety Population: Teprotumumab | Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received. | 0 | 43 | 5 | 43 | 25 | 43 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Optic neuropathy | Eye disorders | MedDRA 14.0 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Inflammatory bowel disease | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Escherichia sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Hashimoto's encephalopathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Urinary retention | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
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Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julie Ball, Executive Director | Horizon Pharma USA, Inc. | clinicaltrials@horizonpharma.com |
| ID | Term |
|---|---|
| D049970 | Graves Ophthalmopathy |
| D005128 | Eye Diseases |
| ID | Term |
|---|---|
| D015785 | Eye Diseases, Hereditary |
| D006111 | Graves Disease |
| D005094 | Exophthalmos |
| D009916 | Orbital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006042 | Goiter |
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C551399 | teprotumumab |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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