Trial Outcomes & Findings for Treatment of Graves' Orbitopathy to Reduce Proptosis With Teprotumumab Infusions in an Open-Label Clinical Extension Study (NCT NCT03461211)

Last Updated: 2024-06-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2024-06-28

Participant Flow

Participants were eligible for enrollment in this study (OPTIC-X) if they completed the 24-week double-masked Treatment Period in Study HZNP-TEP-301 (NCT03298867; OPTIC) and were proptosis non-responders 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.

The Baseline (Day 1) Visit of this extension study occurred within 14 days after the final visit of Study HZNP-TEP-301, which was Week 24 for proptosis non-responders and up to Week 72 for participants who relapsed. The study treatment previously administered in HZNP-TEP-301 (teprotumumab or placebo) remained masked throughout this extension study.

Participant milestones

Participant milestones
Measure	Teprotumumab (OPTIC Placebo) Participants who received placebo in OPTIC received 8 infusions of open-label 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.	Teprotumumab (OPTIC Teprotumumab) Participants who received teprotumumab in OPTIC received 8 infusions of open-label 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.
Overall Study STARTED	37	14
Overall Study Proptosis Non-Responders in OPTIC	36	5
Overall Study Relapsed During Follow-Up Period of OPTIC	1	9
Overall Study COMPLETED	36	12
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Teprotumumab (OPTIC Placebo) Participants who received placebo in OPTIC received 8 infusions of open-label 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.	Teprotumumab (OPTIC Teprotumumab) Participants who received teprotumumab in OPTIC received 8 infusions of open-label 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.
Overall Study Adverse Event	1	1
Overall Study Lack of Efficacy	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Teprotumumab (OPTIC Placebo) n=37 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=14 Participants Participants who received teprotumumab in OPTIC received 8 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.	Total n=51 Participants Total of all reporting groups
Age, Continuous	48.5 years STANDARD_DEVIATION 13.49 • n=5 Participants	56.1 years STANDARD_DEVIATION 11.52 • n=7 Participants	50.6 years STANDARD_DEVIATION 13.32 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	11 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	14 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	33 Participants n=5 Participants	11 Participants n=7 Participants	44 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Intent-to-Treat Population: all participants enrolled in the study. Participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic. One participant in the Teprotumumab (OPTIC Teprotumumab) arm was excluded from all Week 24 summaries due to COVID-19 (visit delayed).

Outcome measures

Outcome measures
Measure	Teprotumumab (OPTIC Placebo) n=37 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=13 Participants Participants who received teprotumumab in OPTIC received 8 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.
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	89.2 percentage of participants	53.8 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-Treat Population: all participants enrolled in the study. Participants with CAS \> 1 at Study Baseline. Per the statistical analysis plan, participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic. One participant in the Teprotumumab (OPTIC Teprotumumab) arm was excluded from all Week 24 summaries due to COVID-19 (visit delayed).

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.

Outcome measures

Outcome measures
Measure	Teprotumumab (OPTIC Placebo) n=32 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=11 Participants Participants who received teprotumumab in OPTIC received 8 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.
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	65.6 percentage of participants	36.4 percentage of participants

SECONDARY outcome

Timeframe: Study Baseline, Week 24

Population: Intent-to-Treat Population: all participants enrolled in the study. Participants with both baseline and Week 24 measurements. One participant in the Teprotumumab (OPTIC Teprotumumab) arm was excluded from all Week 24 summaries due to COVID-19 (visit delayed).

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

Outcome measures

Outcome measures
Measure	Teprotumumab (OPTIC Placebo) n=36 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=11 Participants Participants who received teprotumumab in OPTIC received 8 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.
Change in Proptosis From Baseline to Week 24	-3.47 mm Standard Deviation 1.732	-1.77 mm Standard Deviation 1.126

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-Treat Population: all participants enrolled in the study. Participants with diplopia at Study Baseline. Per the statistical analysis plan, participants missing Week 24 values were considered non-responders, aside from those with missing data related to the COVID-19 pandemic. One participant in the Teprotumumab (OPTIC Teprotumumab) arm was excluded from all Week 24 summaries due to COVID-19 (visit delayed).

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.

Outcome measures

Outcome measures
Measure	Teprotumumab (OPTIC Placebo) n=23 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=4 Participants Participants who received teprotumumab in OPTIC received 8 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.
Percentage of Participants Who Were Diplopia Responders at Week 24	60.9 percentage of participants	75.0 percentage of participants

SECONDARY outcome

Timeframe: Study Baseline, Week 24

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.

Outcome measures

Outcome measures
Measure	Teprotumumab (OPTIC Placebo) n=36 Participants Participants who received placebo in OPTIC received 8 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.	Teprotumumab (OPTIC Teprotumumab) n=11 Participants Participants who received teprotumumab in OPTIC received 8 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.
Mean Change From Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score	13.39 score on a scale Standard Deviation 17.890	14.73 score on a scale Standard Deviation 11.777

Adverse Events

Treatment Period: Teprotumumab (OPTIC Placebo)

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Treatment Period: Teprotumumab (OPTIC Teprotumumab)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Follow-Up Period: No Treatment (OPTIC Placebo)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Follow-Up Period: No Treatment (OPTIC Teprotumumab)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Period: Teprotumumab (OPTIC Placebo) n=37 participants at risk Participants who received placebo in OPTIC received 8 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.	Treatment Period: Teprotumumab (OPTIC Teprotumumab) n=14 participants at risk Participants who received teprotumumab in OPTIC received 8 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.	Follow-Up Period: No Treatment (OPTIC Placebo) n=36 participants at risk Participants who received placebo in OPTIC and were proptosis non-responders. Participants received 8 infusions of teprotumumab q3W for a total of 21 weeks in OPTIC-X and entered a 24-week Follow-up Period; no trial drug was administered.	Follow-Up Period: No Treatment (OPTIC Teprotumumab) n=4 participants at risk Participants who received teprotumumab in OPTIC and were proptosis non-responders. Participants received 8 infusions of teprotumumab q3W for a total of 21 weeks in OPTIC-X and entered a 24-week Follow-up Period; no trial drug was administered.
Nervous system disorders Cerebral Haemorrhage	0.00% 0/37 • All-Cause Mortality and Serious Adverse Events (AEs): from informed consent through 30 days after study discontinuation. Mean days on study was 332.9 and 218.8 for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively. Non-serious AEs: from first dose of study drug through last dose of study drug + 3 weeks (Treatment Period; mean 168.1 and 170.9 days for Placebo and Teprotumumab arms, respectively) or from Week 24 up to Week 48 in the Follow-Up Period (mean 170.1 and 165.0 days for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively).	7.1% 1/14 • All-Cause Mortality and Serious Adverse Events (AEs): from informed consent through 30 days after study discontinuation. Mean days on study was 332.9 and 218.8 for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively. Non-serious AEs: from first dose of study drug through last dose of study drug + 3 weeks (Treatment Period; mean 168.1 and 170.9 days for Placebo and Teprotumumab arms, respectively) or from Week 24 up to Week 48 in the Follow-Up Period (mean 170.1 and 165.0 days for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively).	0.00% 0/36 • All-Cause Mortality and Serious Adverse Events (AEs): from informed consent through 30 days after study discontinuation. Mean days on study was 332.9 and 218.8 for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively. Non-serious AEs: from first dose of study drug through last dose of study drug + 3 weeks (Treatment Period; mean 168.1 and 170.9 days for Placebo and Teprotumumab arms, respectively) or from Week 24 up to Week 48 in the Follow-Up Period (mean 170.1 and 165.0 days for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively).	0.00% 0/4 • All-Cause Mortality and Serious Adverse Events (AEs): from informed consent through 30 days after study discontinuation. Mean days on study was 332.9 and 218.8 for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively. Non-serious AEs: from first dose of study drug through last dose of study drug + 3 weeks (Treatment Period; mean 168.1 and 170.9 days for Placebo and Teprotumumab arms, respectively) or from Week 24 up to Week 48 in the Follow-Up Period (mean 170.1 and 165.0 days for Teprotumumab (OPTIC Placebo) and Teprotumumab (OPTIC Teprotumumab) arms, respectively).

Other adverse events

Additional Information

Roxann Becco

Horizon Pharma USA, Inc.

Phone: 866-479-6742

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
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