Trial Outcomes & Findings for Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (NCT NCT03298867)

Last Updated: 2024-07-11

Results Overview

Proptosis responders were defined as participants with a ≥2 mm reduction from Baseline in proptosis in the study eye, without deterioration (≥2 mm increase) of proptosis in the fellow eye at Week 24.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

83 participants

Primary outcome timeframe

Week 24

Results posted on

2024-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Eight infusions of placebo every 3 weeks (q3W) for a total of 21 weeks.	Teprotumumab 20 mg/kg Eight infusions of teprotumumab every 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.
Double-Masked 24-Week Treatment Period STARTED	42	41
Double-Masked 24-Week Treatment Period COMPLETED	40	39
Double-Masked 24-Week Treatment Period NOT COMPLETED	2	2
48-Week Follow-Up Period (Weeks 24-72) STARTED	4	36
48-Week Follow-Up Period (Weeks 24-72) COMPLETED	3	20
48-Week Follow-Up Period (Weeks 24-72) NOT COMPLETED	1	16
48-Week Follow-Up Contact (Weeks 96-120) STARTED	3	20
48-Week Follow-Up Contact (Weeks 96-120) COMPLETED	3	19
48-Week Follow-Up Contact (Weeks 96-120) NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eight infusions of placebo every 3 weeks (q3W) for a total of 21 weeks.	Teprotumumab 20 mg/kg Eight infusions of teprotumumab every 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.
Double-Masked 24-Week Treatment Period Adverse Event	1	1
Double-Masked 24-Week Treatment Period Withdrawal by Subject	1	1
48-Week Follow-Up Period (Weeks 24-72) Relapsed/Entered OPTIC-X	1	9
48-Week Follow-Up Period (Weeks 24-72) Relapsed/Did not enter OPTIC-X	0	1
48-Week Follow-Up Period (Weeks 24-72) Physician Decision	0	1
48-Week Follow-Up Period (Weeks 24-72) Withdrawal by Subject	0	2
48-Week Follow-Up Period (Weeks 24-72) Other, Not Specified	0	1
48-Week Follow-Up Period (Weeks 24-72) Mis-classified as Responders	0	2
48-Week Follow-Up Contact (Weeks 96-120) Lost to Follow-up	0	1

Baseline Characteristics

Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis With Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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=83 Participants Total of all reporting groups
Age, Continuous	48.9 years STANDARD_DEVIATION 12.96 • n=5 Participants	51.6 years STANDARD_DEVIATION 12.63 • n=7 Participants	50.2 years STANDARD_DEVIATION 12.79 • n=5 Participants
Age, Customized <65 years	38 Participants n=5 Participants	32 Participants n=7 Participants	70 Participants n=5 Participants
Age, Customized ≥65 years	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=5 Participants	39 Participants n=7 Participants	80 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	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White	37 Participants n=5 Participants	35 Participants n=7 Participants	72 Participants n=5 Participants
Race/Ethnicity, Customized More Than 1 Race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Tobacco use status - as randomized Non-User	33 Participants n=5 Participants	32 Participants n=7 Participants	65 Participants n=5 Participants
Tobacco use status - as randomized User	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Tobacco use status - actual Non-User	34 Participants n=5 Participants	32 Participants n=7 Participants	66 Participants n=5 Participants
Tobacco use status - actual User	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-treat population: all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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 Proptosis Responders at Week 24	9.5 percentage of participants	82.9 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat population: all randomized participants.

Overall responders were defined as participants with a ≥2 mm reduction in proptosis AND a ≥2 point reduction in Clinical Activity Score (CAS) from Baseline in the study eye, without deterioration (≥2 mm increase in proptosis or ≥2 point increase in CAS) in the fellow eye at Week 24. The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no clinical activity) to 7 (most clinical activity).

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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 Overall Responders at Week 24	7.1 percentage of participants	78.0 percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat population: all randomized participants.

CAS categorical responders were defined as participants with a reduction to a CAS of 0 or 1 (no or minimal inflammatory symptoms) in study eye. The CAS is a 7-item description of clinical activity, including: 1. Spontaneous orbital pain; 2. Gaze evoked orbital pain; 3. Eyelid swelling that is considered to be due to active (inflammatory phase) thyroid eye disease/ Graves' Ophthalmopathy or Orbitopathy (TED/GO); 4. Eyelid erythema; 5. Conjunctival redness that is considered to be due to active (inflammatory phase) TED/GO (ignore "equivocal" redness); 6. Chemosis; 7. Inflammation of caruncle or plica. Each item is scored (1=present; 0=absent) and scores for each item are summed for total score of 0 (no inflammatory symptoms) to 7 (most inflammatory symptoms).

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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 CAS Categorical Responders at Week 24 (Study Eye)	21.4 percentage of participants	58.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, up to Week 24

Population: Intent-to-treat population: all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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 From Baseline in Proptosis to Week 24 (Study Eye)	-0.54 mm Standard Error 0.192	-2.82 mm Standard Error 0.191

SECONDARY outcome

Timeframe: Week 24

Population: Intent-to-treat population: all randomized participants with diplopia at baseline in the study eye.

Diplopia responders were defined as participants with Baseline diplopia Subjective Diplopia Score grade \>0 in the study eye who had a reduction of ≥1 grade with no corresponding deterioration (≥1 grade worsening) in the fellow eye at Week 24. Denominator is the number of subjects with diplopia at Baseline. The Subjective Diplopia Score is a clinical measure of diplopia severity on a grade scale of 0 to 3: 0=no diplopia; 1=intermittent (diplopia in primary position of gaze, when tired or when first awakening); 2=inconstant (diplopia at extremes of gaze); 3=constant (continuous diplopia in primary or reading position).

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=28 Participants Eight infusions of teprotumumab 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	28.6 percentage of participants	67.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, up to Week 24

Population: Intent-to-treat population: all randomized participants.

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 subjects on (i) their daily physical activity as it relates to visual function, and (ii) psychosocial functioning. The range of the GO-QoL overall transformed scores is 0 to 100, where higher values correspond to better quality of life.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 Participants Eight infusions of teprotumumab 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 From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24	4.43 score on a scale Standard Error 2.102	13.79 score on a scale Standard Error 2.074

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Teprotumumab 20 mg/kg

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=42 participants at risk Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 participants at risk Eight infusions of teprotumumab 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.
Nervous system disorders Visual field defect	2.4% 1/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	0.00% 0/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	2.4% 1/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	2.4% 1/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.

Other adverse events

Additional Information

Suzy Hammel

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 or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=42 participants at risk Eight infusions of placebo q3W for a total of 21 weeks.	Teprotumumab 20 mg/kg n=41 participants at risk Eight infusions of teprotumumab 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.
Gastrointestinal disorders Abdominal Pain Upper	7.1% 3/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	4.9% 2/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Gastrointestinal disorders Diarrhoea	11.9% 5/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	12.2% 5/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Gastrointestinal disorders Nausea	9.5% 4/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	14.6% 6/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Gastrointestinal disorders Stomatitis	2.4% 1/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	7.3% 3/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
General disorders Fatigue	2.4% 1/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	12.2% 5/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Infections and infestations Influenza	7.1% 3/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	2.4% 1/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Musculoskeletal and connective tissue disorders Muscle Spasms	9.5% 4/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	34.1% 14/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Nervous system disorders Dizziness	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	7.3% 3/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Nervous system disorders Dysgeusia	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	9.8% 4/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Nervous system disorders Headache	9.5% 4/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	9.8% 4/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	9.8% 4/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	4.9% 2/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Skin and subcutaneous tissue disorders Alopecia	11.9% 5/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	24.4% 10/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	12.2% 5/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.
Skin and subcutaneous tissue disorders Madarosis	0.00% 0/42 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.	7.3% 3/41 • From first dose of study drug through the end of the Double-Masked Treatment Period (up to 24 weeks) plus 3 weeks.