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

Primary Purpose

Thyroid Eye Disease

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Teprotumumab

About this trial

This is an interventional treatment trial for Thyroid Eye Disease

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 upper limit of normal (ULN; according to age) at the most recent clinic visit.
Diabetic participants must have well-controlled disease (defined as hemoglobin A1C [HbA1c] < 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.

Sites / Locations

Macro, Llc
Cedars-Sinai Medical Center
Bascom Palmer Eye Institute
Kellogg Eye Center at University of Michigan
Casey Eye Institute at Oregon Health and Science
Hamilton Eye Institute at University of Tennessee Health
Eye Wellness Center
Medical College of Wisconsin, The Eye Institute
University Hospital Essen, Department of Ophthalmology
Johannes Gutenberg University Medical Center
Fondazione IRCCS Ca Granda Ospedale Maggiore
University of Pisa, Department of Clinical and Experimental Medicine
Azienda Ospedaliero Universitaria Pisana

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Teprotumumab

Arm Description

Eight infusions of teprotumumab every 3 weeks (q3W) for a total of 21 weeks: teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.

Outcomes

Primary Outcome Measures

Percentage of Participants With a ≥ 2 mm Reduction From Baseline in the Study Eye Without Deterioration of Proptosis in the Fellow Eye at Week 24

Proptosis responders were defined as participants with a ≥ 2 mm reduction from study baseline in proptosis in the study eye, without deterioration (≥ 2 mm increase) of proptosis in the fellow eye at Week 24. Participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic.

Secondary Outcome Measures

Percentage of Participants With a European Group on Graves' Ophthalmopathy (EUGOGO) Amended Clinical Activity Score (CAS) Total Score of 0 or 1 in the Study Eye at Week 24

CAS responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) as a categorical response variable at Week 24. The 7-item CAS assigns 1 point for each of the following items present in the study eye: spontaneous orbital pain; gaze evoked orbital pain; eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/Graves' ophthalmopathy (TED/GO); eyelid erythema; conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); chemosis; inflammation of caruncle or plica. The sum of these points is the total score (0 to 7), with higher scores indicating worse symptoms.

Change in Proptosis From Baseline to Week 24

Mean change from study baseline to Week 24 in proptosis measurement (mm) in the study eye at Week 24.

Percentage of Participants Who Were Diplopia Responders at Week 24

Diplopia responders were defined as participants with 1 grade or greater reduction in diplopia score in the study eye without worsening by at least 1 grade in the fellow eye at Week 24. The subjective diplopia score (0=no diplopia; 1=intermittent, i.e. diplopia in primary position of gaze, when tired or when first awakening; 2=inconstant, i.e. diplopia at extremes of gaze; 3=constant, i.e. continuous diplopia in primary or reading position) was recorded for each eye. A participant was considered to have diplopia if a score > 0 is observed in the study eye at study baseline.

Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score

The GO-QoL is a 16-item self-administered questionnaire divided into 2 subsets and used to assess the perceived effects of TED by the participants on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The sum of the scores from each set of 8 questions was calculated and transformed to a scale from 0 (worst) to 100 (best) - one for visual function (VF), one for appearance (A) and one for the overall combined (VF + A) score. Scores were transformed as follows: Transformed score = [(sum of each score - number of completed items) / (2 * number of completed items)] * 100. The "overall combined (VF + A) score" is also 0 to 100, with higher scores indicating a better outcome.

Full Information

NCT ID

NCT03461211

First Posted

March 5, 2018

Last Updated

December 9, 2021

Sponsor

Horizon Pharma USA, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03461211

Brief Title

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

Acronym

OPTIC-X

Official Title

Multicenter, Safety and Efficacy, Open-Label Extension Study Evaluating Teprotumumab (HZN-001) Treatment in Subjects With Thyroid Eye Disease

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

April 16, 2018 (Actual)

Primary Completion Date

June 8, 2020 (Actual)

Study Completion Date

February 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Horizon Pharma USA, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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; OPTIC) and who were either proptosis non-responders at Week 24 of HZNP-TEP-301 or were proptosis responders at Week 24 but met the criteria for re-treatment due to relapse during the Follow-Up Period of HZNP-TEP-301.

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 are 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thyroid Eye Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

51 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Teprotumumab

Arm Type

Experimental

Arm Description

Eight infusions of teprotumumab every 3 weeks (q3W) for a total of 21 weeks: teprotumumab 10 mg/kg administered on Day 1 and teprotumumab 20 mg/kg administered q3W for the remaining 7 infusions.

Intervention Type

Biological

Intervention Name(s)

Teprotumumab

Other Intervention Name(s)

HZN-001

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. 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).

Primary Outcome Measure Information:

Title

Percentage of Participants With a ≥ 2 mm Reduction From Baseline in the Study Eye Without Deterioration of Proptosis in the Fellow Eye at Week 24

Description

Time Frame

Baseline, Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants With a European Group on Graves' Ophthalmopathy (EUGOGO) Amended Clinical Activity Score (CAS) Total Score of 0 or 1 in the Study Eye at Week 24

Description

Time Frame

Week 24

Title

Change in Proptosis From Baseline to Week 24

Description

Mean change from study baseline to Week 24 in proptosis measurement (mm) in the study eye at Week 24.

Time Frame

Study Baseline, Week 24

Title

Percentage of Participants Who Were Diplopia Responders at Week 24

Description

Time Frame

Week 24

Title

Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score

Description

Time Frame

Study Baseline, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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 upper limit of normal (ULN; according to age) at the most recent clinic visit. Diabetic participants must have well-controlled disease (defined as hemoglobin A1C [HbA1c] < 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raymond Douglas, MD, PhD

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

George Kahaly, MD, PhD

Organizational Affiliation

Johannes Gutenberg University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Macro, Llc

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90212

Country

United States

Facility Name

Cedars-Sinai Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90078

Country

United States

Facility Name

Bascom Palmer Eye Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33135

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

Casey Eye Institute at Oregon Health and Science

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Hamilton Eye Institute at University of Tennessee Health

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

University Hospital Essen, Department of Ophthalmology

City

Essen

ZIP/Postal Code

45147

Country

Germany

Facility Name

Johannes Gutenberg University Medical Center

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Fondazione IRCCS Ca Granda Ospedale Maggiore

City

Milan

ZIP/Postal Code

20122

Country

Italy

Facility Name

University of Pisa, Department of Clinical and Experimental Medicine

City

Pisa

ZIP/Postal Code

56100

Country

Italy

Facility Name

Azienda Ospedaliero Universitaria Pisana

City

Pisa

ZIP/Postal Code

56124

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

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

Links:

URL

http://www.TEPEZZA.com

Description

Related Info

Learn more about this trial

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

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