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Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X)

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ClinicalTrials.gov Identifier: NCT03461211
Recruitment Status : Enrolling by invitation
First Posted : March 9, 2018
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Brief Summary:
The overall objective is to evaluate the safety and efficacy of teprotumumab in the treatment of Thyroid Eye Disease (TED) in participants who participated in the lead-in study HZNP-TEP-301 (NCT03298867) and who were either proptosis non-responders at Week 24 of HZNP-TEP-301 or were proptosis responders at Week 24 but meet the criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301.

Condition or disease Intervention/treatment Phase
Thyroid Eye Disease Biological: Teprotumumab Phase 3

Detailed Description:

This is a multi-center, open-label extension study of HZNP-TEP-301 (NCT03298867) examining the safety and efficacy of teprotumumab in the treatment of TED in adult participants. Participants who complete the 24-week double-masked Treatment Period in Study HZNP-TEP-301 and are proptosis non-responders or were proptosis responders at Week 24 but meet the criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301 will be eligible for enrollment.

All participants who choose to participate will receive 8 infusions of teprotumumab (10 mg/kg for the first infusion followed by 20 mg/kg for the remaining 7 infusions) in an open-label fashion.The Baseline (Day 1) Visit of this extension study will occur within 14 days after the final visit of Study HZNP-TEP-301 (Week 24 for proptosis non-responders and up to Week 72 for participants who relapse). During the open-label Treatment Period, study drug infusions are scheduled for Day 1 (Baseline), and Weeks 3, 6, 9, 12, 15, 18, and 21, (with the final visit at Week 24). After completion of the Treatment Period, subjects who were proptosis non-responders in Study HZNP-TEP-301 will enter a 24-week Follow-Up Period during which study drug will not be administered and clinic visits are scheduled for 1, 3, and 6 months (Visits Month 7, 9, and 12) after the Week 24 visit. Subjects will be contacted 6 and 12 months later by phone or email to enquire if any treatment for TED had been received since the last study contact.

Participants who relapse during the Follow-Up Period of HZNP-TEP-301 and choose to enter this extension study will not participate in the Follow-Up Period of this study but will be contacted by phone or email 6 and 12 months after the Week 24 visit.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Safety and Efficacy, Open-Label Extension Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Thyroid Eye Disease
Actual Study Start Date : April 16, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).
Biological: Teprotumumab
Approximately 50 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.




Primary Outcome Measures :
  1. Effect of teprotumumab on the proptosis responder rate at the end of treatment 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.


Secondary Outcome Measures :
  1. Percentage of participants with a Clinical Activity Score (CAS) value of 0 or 1 at Week 24 in the study eye [ Time Frame: Week 24 ]
  2. Mean change from Baseline to Week 24 in proptosis measurement in the study eye [ Time Frame: Week 24 ]
  3. Effect of teprotumumab on the diplopia responder rate at Week 24 [ Time Frame: Week 24 ]
    The percentage of participants with baseline diplopia > 0 in study eye who have a reduction of ≥ 1 grade with no corresponding deterioration [≥ 1 grade worsening] in the fellow eye) at Week 24.

  4. Mean change from Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score [ Time Frame: Week 24 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent.
  • Completed the 24-week double-masked Treatment Period in Study HZNP-TEP-301 (NCT03298867).
  • Proptosis non-responder (< 2 mm reduction in proptosis in the study eye) at Week 24 of Study HZNP-TEP-301 OR proptosis responder at Week 24 who relapses during the Follow-Up Period of Study HZNP-TEP-301.
  • Participant must be euthyroid with the baseline disease under control, or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels < 50% above or below the normal limits) at the most recent clinic visit. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the clinical trial.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 times the upper limit of normal (ULN) or serum creatinine <1.5 times the ULN (according to age) at the most recent clinic visit.
  • Diabetic participants must have well-controlled disease (defined as HgbA1c < 9.0% at most recent clinic visit).
  • Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the study.
  • Women of childbearing potential must have a negative urine pregnancy test at Baseline/Day 1. Participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial and continue for 180 days after the last dose of study drug. One of the 2 forms of contraception is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be in use for at least one full cycle prior to Baseline. Highly effective contraceptive methods (with a failure rate less than 1% per year), when used consistently and correctly, includes implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner.
  • Male participants must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use a barrier contraceptive method from Baseline through 180 days after the last dose of study drug.
  • Participant is willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
  • Has not received any treatment for TED since Week 24 of the of the HZNP-TEP-301 study.

Exclusion Criteria:

  • Participants will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the study protocol or have a concomitant disease or condition that could interfere with the conduct of the study or potentially put the participant at unacceptable risk.
  • The exclusion criteria (except those related to screening) of protocol HZNP-TEP-301(NCT03298867) also apply to this open-label extension study.

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): NCT03461211


Locations
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United States, California
Macro, Llc
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, 33135
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
Portland, Oregon, United States, 97239
United States, Tennessee
Hamilton Eye Institute at University of Tennessee Health
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
University Hospital Essen, Department of Ophthalmology
Essen, Germany, 45147
Johannes Gutenberg University Medical Center
Mainz, Germany, 55131
Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore
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
Sponsors and Collaborators
Horizon Pharma USA, Inc.
Investigators
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Principal Investigator: Raymond Douglas, MD, PhD Cedars-Sinai Medical Center
Principal Investigator: George Kahaly, MD, PhD Johannes Gutenberg University Medical Center

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Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT03461211     History of Changes
Other Study ID Numbers: HZNP-TEP-302
2017-002713-58 ( EudraCT Number )
First Posted: March 9, 2018    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Thyroid Diseases
Eye Diseases
Graves Ophthalmopathy
Endocrine System Diseases
Eye Diseases, Hereditary
Graves Disease
Exophthalmos
Orbital Diseases
Genetic Diseases, Inborn
Goiter
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs