TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study
Primary Purpose
Thyroid Eye Disease
Status
Active
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Teprotumumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Thyroid Eye Disease focused on measuring TED
Eligibility Criteria
Inclusion Criteria:
- Written informed consent.
- Male or female between the ages of 18 and 80 years, inclusive, at Screening.
- Initial diagnosis of TED within 7 years prior to Screening.
- Proptosis ≥3 mm from baseline (prior to diagnosis of TED), as estimated by treating physician, and/or proptosis >3 mm above normal for race and gender.
- Participants must be euthyroid with the baseline disease under control or have mild hypo or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels <50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the duration of the trial.
- Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
- Diabetic participants must have HbA1c ≤8.0% at Screening.
- Participants with a history of IBD (ulcerative colitis or Crohn's disease) must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to Screening and no planned surgery during the trial. Concomitant stable therapies for IBD without modifications in the 3 months prior to Screening are allowed.
- Women of childbearing potential (including those with an onset of menopause <2 years prior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening or not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (i.e., prior to each dose and throughout the participant's participation in the Follow-up Period); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of teprotumumab. Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, tubal ligation, sexual abstinence or vasectomized partner.
- Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
Exclusion Criteria:
- Decreased best-corrected visual acuity due to optic neuropathy, as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
- Corneal decompensation unresponsive to medical management.
- Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
- Prior orbital irradiation, orbital decompression or strabismus surgery.
- Planned eyelid surgery during the course of the trial.
- Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73m2 at Screening.
- Use of any steroid (intravenous [IV], oral, steroid eye drops) for the treatment of TED or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids, as well as steroids used to treat infusion reactions.
- Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of teprotumumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.
- Any previous treatment with teprotumumab, including previous enrollment in this trial or participation in a prior teprotumumab trial.
- Treatment with any mAb within 3 months prior to Screening.
- Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
- Use of an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
- Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
- Pregnant or lactating women.
- Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
- Known hypersensitivity to any of the components of teprotumumab or prior hypersensitivity reactions to mAbs.
- Human immunodeficiency virus, untreated or positive viral load for hepatitis C or hepatitis B infections.
- Any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.
- After 150 participants with a CAS <3 at Baseline have been randomized, an additional exclusion criterion will apply: CAS <3 at Baseline.
Sites / Locations
- UCLA Health, Beverley Hills Primary & Specialty care
- USC Roski Eye Institute - Los Angeles
- Stanford University
- University of Colorado - Eye Center
- Bascom Palmer Eye Institute
- Mayo Clinic
- Washington University in St. Louis
- University of Nebraska Medical Center
- Casey Eye Institute - OHSU
- The Medical College of Wisconsin, Inc.
- Hopital Jean Minjoz
- Hôpital Louis Pradel
- Hôpital Claude Huriez
- Centre Hospitalier National D'ophtalmologie Des Quinze Vingts
- Universitätsklinikum Tübingen
- University Medicine Göttingen Germany
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- Universitätsklinikum Essen
- Universitätsklinikum Münster
- Azienda Ospedaliera Universitaria Federico II
- ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi
- Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
- Azienda Ospedaliero Universitaria Pisana
- University of Pisa
- Hospital La Arruzafa
- Hospital Universitario Ramon Y Cajal
- Hospital Universitario Virgen Macarena
- Moorfields Eye Hospital
- Imperial College Healthcare NHS Trust
- University Hospital of Cardiff
- Royal Victoria Infirmary, Newcastle Eye Centre
- Southampton Eye Unit
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
Teprotumumab 4 Infusions
Teprotumumab 8 Infusions
Teprotumumab 16 Infusions
Arm Description
• 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of: Placebo if a participant is a treatment responder at Week 12 or Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12
8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)
16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)
Outcomes
Primary Outcome Measures
Percentage of Participants who experience at least 1 treatment-emergent adverse event (TEAE) and the percentage of participants who experience at least 1 treatment emergent AESI during treatment with teprotumumab
Treatment emergent adverse events and treatment emergent adverse events of special interest will be evaluated from the beginning of the study until follow up.
Percentage of Participants who receive re-treatment
Participants who are not proptosis responders after initial treatment or participants who are proptosis responders after initial treatment but who have flared during follow-up (relapsed).
Secondary Outcome Measures
Full Information
NCT ID
NCT05002998
First Posted
July 19, 2021
Last Updated
September 6, 2023
Sponsor
Horizon Therapeutics USA, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05002998
Brief Title
TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study
Official Title
A Phase 3b/4, Double-masked, Randomized, International, Parallel-assignment, Multicenter Trial in Patients With Thyroid Eye Disease to Evaluate the Safety and Tolerability of Different Dosing Durations of Teprotumumab
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 16, 2021 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Horizon Therapeutics USA, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a double-masked, randomized, parallel-assignment, multicenter trial examining the safety and tolerability of teprotumumab in the treatment of Thyroid Eye Disease (TED) in adult participants. This international, Phase 3b/4 trial is being conducted to fulfill an FDA post-marketing requirement for a descriptive trial to evaluate the safety, efficacy and need for re-treatment of 3 different teprotumumab treatment durations for TED. In addition, serum samples from participants with a Baseline Clinical Activity Score (CAS) ≥3 will be evaluated for biomarkers of disease.
Detailed Description
Participants will be screened for eligibility within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio in a double-masked fashion (stratified by CAS(clinical activity score) [≥3 (active) or <3 (inactive)] and disease severity [severe disease, defined as both proptosis above normal for race and gender with binocular diplopia at Baseline vs. non-severe disease]) to receive:
4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of:
Placebo if a participants is a treatment responder at Week 12 or
Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12
8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)
16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)
Three weeks following the final infusion of the Initial Treatment Period, there will be a comprehensive End-of-Initial Treatment Visit at Week 24 (Cohorts 1 and 2)/Week 48 (Cohort 3). At this visit, all participants will be assessed for treatment response.
Proptosis responders in all cohorts and non-responders in Cohorts 1 and 2 who choose not to receive a second treatment course, will enter a 52 week Initial Follow-up Period.
Proptosis non-responders in Cohorts 1 and 2 who choose to receive a second treatment course (8 infusions) of teprotumumab will receive an infusion q3W.
Proptosis non-responders in Cohort 3 are not eligible for a second treatment course following initial treatment.
Participants in any of the 3 cohorts who are proptosis responders following the Initial Treatment Period and who flare during the Initial Follow up Period will be eligible to receive re treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Eye Disease
Keywords
TED
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of:
Placebo if a participant is a treatment responder at Week 12 or
Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12
8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)
16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-masked except for the pharmacy staff.
Allocation
Randomized
Enrollment
313 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Teprotumumab 4 Infusions
Arm Type
Other
Arm Description
• 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of:
Placebo if a participant is a treatment responder at Week 12 or
Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12
Arm Title
Teprotumumab 8 Infusions
Arm Type
Other
Arm Description
8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)
Arm Title
Teprotumumab 16 Infusions
Arm Type
Other
Arm Description
16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)
Intervention Type
Drug
Intervention Name(s)
Teprotumumab
Other Intervention Name(s)
TEPEZZA
Intervention Description
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 containing, in addition to the drug substance, 20 mmol/L histidine-histidine chloride, 250 mmol/L trehalose and 0.01% polysorbate 20 (w/w).
Prior to administration, each vial containing 500 mg teprotumumab freeze-dried powder will be reconstituted with 10 mL of sterile water for injection. The resulting solution will have a concentration of 47.6 mg/mL teprotumumab-trbw antibody. The reconstituted teprotumumab solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline Solution
Intervention Description
Placebo will consist of a normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as appropriate, per weight-based dosing volumes.
Primary Outcome Measure Information:
Title
Percentage of Participants who experience at least 1 treatment-emergent adverse event (TEAE) and the percentage of participants who experience at least 1 treatment emergent AESI during treatment with teprotumumab
Description
Treatment emergent adverse events and treatment emergent adverse events of special interest will be evaluated from the beginning of the study until follow up.
Time Frame
Screening to End of Study (last visit possible is Week 136)
Title
Percentage of Participants who receive re-treatment
Description
Participants who are not proptosis responders after initial treatment or participants who are proptosis responders after initial treatment but who have flared during follow-up (relapsed).
Time Frame
Week 27 to Week 136
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent.
Male or female between the ages of 18 and 80 years, inclusive, at Screening.
Initial diagnosis of TED within 7 years prior to Screening.
Proptosis ≥3 mm from baseline (prior to diagnosis of TED), as estimated by treating physician, and/or proptosis >3 mm above normal for race and gender.
Participants must be euthyroid with the baseline disease under control or have mild hypo or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels <50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the duration of the trial.
Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
Diabetic participants must have HbA1c ≤8.0% at Screening.
Participants with a history of IBD (ulcerative colitis or Crohn's disease) must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to Screening and no planned surgery during the trial. Concomitant stable therapies for IBD without modifications in the 3 months prior to Screening are allowed.
Women of childbearing potential (including those with an onset of menopause <2 years prior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening or not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (i.e., prior to each dose and throughout the participant's participation in the Follow-up Period); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of teprotumumab. Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, tubal ligation, sexual abstinence or vasectomized partner.
Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
Exclusion Criteria:
Decreased best-corrected visual acuity due to optic neuropathy, as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
Corneal decompensation unresponsive to medical management.
Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
Prior orbital irradiation, orbital decompression or strabismus surgery.
Planned eyelid surgery during the course of the trial.
Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73m2 at Screening.
Use of any steroid (intravenous [IV], oral, steroid eye drops) for the treatment of TED or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids, as well as steroids used to treat infusion reactions.
Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of teprotumumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.
Any previous treatment with teprotumumab, including previous enrollment in this trial or participation in a prior teprotumumab trial.
Treatment with any mAb within 3 months prior to Screening.
Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
Use of an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
Pregnant or lactating women.
Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
Known hypersensitivity to any of the components of teprotumumab or prior hypersensitivity reactions to mAbs.
Human immunodeficiency virus, untreated or positive viral load for hepatitis C or hepatitis B infections.
Any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.
After 150 participants with a CAS <3 at Baseline have been randomized, an additional exclusion criterion will apply: CAS <3 at Baseline.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ellen Kim, MD
Organizational Affiliation
Horizon Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Health, Beverley Hills Primary & Specialty care
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90210
Country
United States
Facility Name
USC Roski Eye Institute - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
University of Colorado - Eye Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Bascom Palmer Eye Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Casey Eye Institute - OHSU
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Medical College of Wisconsin, Inc.
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hopital Jean Minjoz
City
Besançon
State/Province
Doubs
ZIP/Postal Code
25030
Country
France
Facility Name
Hôpital Louis Pradel
City
Bron
State/Province
Rhône
ZIP/Postal Code
69677
Country
France
Facility Name
Hôpital Claude Huriez
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Centre Hospitalier National D'ophtalmologie Des Quinze Vingts
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
University Medicine Göttingen Germany
City
Göttingen
State/Province
Niedersachsen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitätsklinikum Münster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi
City
Varese
State/Province
Lombardia
ZIP/Postal Code
21100
Country
Italy
Facility Name
Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95124
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Pisana
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
University of Pisa
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
Hospital La Arruzafa
City
Córdoba
ZIP/Postal Code
14012
Country
Spain
Facility Name
Hospital Universitario Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41071
Country
Spain
Facility Name
Moorfields Eye Hospital
City
London
State/Province
London, City Of
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Facility Name
Imperial College Healthcare NHS Trust
City
London
State/Province
London, City Of
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
University Hospital of Cardiff
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF11 0SN
Country
United Kingdom
Facility Name
Royal Victoria Infirmary, Newcastle Eye Centre
City
Newcastle Upon Tyne
ZIP/Postal Code
NE14LP
Country
United Kingdom
Facility Name
Southampton Eye Unit
City
Southampton
ZIP/Postal Code
S0166YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
http://www.TEPEZZA.com
Description
Related Info
Learn more about this trial
TEPEZZA® (Teprotumumab-trbw) Post-Marketing Requirement Study
We'll reach out to this number within 24 hrs