Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC)
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|ClinicalTrials.gov Identifier: NCT03298867|
Recruitment Status : Active, not recruiting
First Posted : October 2, 2017
Last Update Posted : August 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Eye Disease Graves' Orbitopathy||Biological: Teprotumumab Other: Placebo||Phase 3|
This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study. Approximately 76 participants (38/group) who meet the study eligibility criteria will be randomized on Day 1 in a 1:1 ratio (stratified by tobacco use status) to receive 8 infusions of teprotumumab or placebo q3W. All participants will enter a 24-week double-masked Treatment Period, during which study drug will be infused on Day 1 (Baseline), and Weeks 3, 6, 9, 12, 15, 18, and 21 (with a final visit at Week 24). All study drug dosing will be performed at the clinic under the supervision of clinic staff. On each dosing day, scheduled assessments (except for adverse event [AE] and concomitant medication use monitoring, which will be monitored throughout the clinic visit) will be completed prior to study drug dosing.
At the end of the double-masked Treatment Period (Week 24), participants who are proptosis non-responders (study eye has < 2 mm decrease in proptosis) will be eligible to enter an open-label extension study in which participants may receive up to 8 infusions of teprotumumab in an open-label fashion.
At Week 24, proptosis responders, as well as non-responders who choose not to enroll in the open-label extension study, will enter a 48-week Follow-Up Period, during which study drug will not be administered and clinic visits are scheduled for Weeks 28, 36, 48, 60, and 72. Participants who are considered responders at Week 24 but who meet criteria for re-treatment due to relapse during the Follow-Up Period may enroll in the open-label extension study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||76 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Active Thyroid Eye Disease|
|Actual Study Start Date :||October 24, 2017|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||June 2020|
Active Comparator: Teprotumumab 20 mg/kg
Teprotumumab is a fully human anti-IGF-1R mAb. Teprotumumab will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of teprotumumab must be reconstituted with 10 mL of water for injection. Reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. Teprotumumab will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).
Approximately 38 participants will receive 8 infusions of Teprotumumab q3W for a total of 21 weeks. Teprotumumab 10 mg/kg will be administered on Day 1 and Teprotumumab 20 mg/kg will be administered q3W for the remaining 7 infusions.
Other Name: HZN-001
Placebo Comparator: Placebo
Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses > 1800 mg).
Approximately 38 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.
Other Name: Saline solution
- Effect of teprotumumab versus placebo on the proptosis responder rate at Week 24 [ Time Frame: Week 24 ]The percentage of participants with a ≥ 2 mm reduction from Baseline in the study eye without deterioration [≥ 2 mm increase] of proptosis in the fellow eye.
- Effect of teprotumumab versus placebo on the overall responder rate at week 24 [ Time Frame: Week 24 ]The percentage of participants with ≥ 2-point reduction in Clinical Activity Score [CAS] AND ≥ 2 mm reduction in proptosis from Baseline, provided there is no corresponding deterioration [≥ 2-point/mm increase] in CAS or proptosis in the fellow eye.
- Effect of teprotumumab versus placebo on the percentage of participants with a CAS value of 0 or 1 at Week 24 in the study eye [ Time Frame: Week 24 ]
- Effect of teprotumumab versus placebo on the mean change from Baseline to Week 24 in proptosis measurement in the study eye [ Time Frame: Week 24 ]
- Effect of teprotumumab versus placebo on the mean change from Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score [ Time Frame: Week 24 ]
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): NCT03298867
|United States, California|
|Beverly Hills, California, United States, 90212|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90078|
|United States, Florida|
|The Lennar Foundation Medical|
|Coral Gables, Florida, United States, 33146|
|Bascom Palmer Eye Institute|
|Miami, Florida, United States, 33136|
|United States, Michigan|
|Kellogg Eye Center at University of Michigan|
|Ann Arbor, Michigan, United States, 48105|
|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 Health Science Center|
|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|
|University Hospital Essen, Department of Ophthalmology|
|Essen, Germany, 45147|
|Johannes Gutenberg University Medical Center|
|Mainz, Germany, 55131|
|Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico|
|Milan, Italy, 20122|
|University of Pisa, Department of Clinical and Experimental Medicine|
|Pisa, Italy, 56100|
|University of Pisa,Department of Clinical and Experimental Medicine, Endocrinology Unit|
|Pisa, Italy, 56124|
|Principal Investigator:||Raymond Douglas, MD, PhD||Cedars-Sinai Medical Center|
|Principal Investigator:||George Kahaly, MD, PhD||Johannes Gutenberg University Medical Center|