Trial Outcomes & Findings for Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease (NCT NCT01868997)

NCT ID: NCT01868997

Last Updated: 2024-12-17

Results Overview

Number of participants classified as responders and non-responders at Week 24. Responders were defined as participants with a reduction in clinical activity score (CAS, see Outcome Measure 4 description for details) of ≥ 2 points, and a reduction in proptosis (amount of protrusion of the eye from the orbital rim) of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye. Participants who had no assessment at 24 weeks were considered non-responders.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 88 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2024-12-17

Participant Flow

A total of 88 participants were enrolled (all participants who signed informed consent were considered enrolled in this study); 1 participant was never dosed and early terminated.

Participant milestones

Measure	Placebo A placebo infusion (normal saline) was administered once every 3 weeks (q3W) by intravenous (IV) infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Study STARTED	45	42
Overall Study COMPLETED	38	36
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Measure	Placebo A placebo infusion (normal saline) was administered once every 3 weeks (q3W) by intravenous (IV) infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Study Adverse Event	2	5
Overall Study Lack of Efficacy	2	0
Overall Study Other	3	1

Baseline Characteristics

Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease

Baseline characteristics by cohort

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.	Total n=87 Participants Total of all reporting groups
Age, Continuous	54.1 years STANDARD_DEVIATION 12.87 • n=5 Participants	51.7 years STANDARD_DEVIATION 10.78 • n=7 Participants	52.9 years STANDARD_DEVIATION 11.90 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	28 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo).

Number of participants classified as responders and non-responders at Week 24. Responders were defined as participants with a reduction in clinical activity score (CAS, see Outcome Measure 4 description for details) of ≥ 2 points, and a reduction in proptosis (amount of protrusion of the eye from the orbital rim) of ≥ 2 mm in the study eye, and no deterioration (increase in CAS of ≥ 2 points or increase in proptosis of ≥ 2 mm) in the non-study eye. Participants who had no assessment at 24 weeks were considered non-responders.

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Responder Status at Week 24 Non-Responder / Missing	36 Participants	13 Participants
Responder Status at Week 24 Responder	9 Participants	29 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment.

The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of thyroid eye disorder (TED) by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. The transformed overall score is the sum of scores from all 16 questions to a scale of 0 (worst health) to 100 (best health).

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])	6.77 units on a scale Standard Error 2.251	17.74 units on a scale Standard Error 2.423

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment.

Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements were recorded using the Hertel exophthalmometer. Participants with a decrease ≥ 2 mm were considered improving, those with an increase or decrease < 2 mm were considered remaining stable, and those with an increase ≥ 2 mm were considered worsening.

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)	-0.15 mm Standard Error 0.188	-2.46 mm Standard Error 0.200

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment.

The 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amended CAS was used to evaluate clinical activity. For each of the following items, one point is given: spontaneous orbital pain, gaze evoked orbital pain, eyelid swelling that is considered to be due to active (inflammatory phase) Graves' ophthalmopathy (GO), eyelid erythema, conjunctival redness that is considered to be due to active (inflammatory phase) GO, chemosis, and inflammation of caruncle or plica. The sum of these points is the total score, with 0 indicating no clinical activity and 7 indicating the most severe clinical activity.

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Average Change From Baseline in CAS to Week 24 (MMRM)	-1.85 units on a scale Standard Error 0.172	-3.43 units on a scale Standard Error 0.181

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment.

The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Visual Functioning score is the sum of scores from following 8 questions to a scale of 0 (worst health) to 100 (best health): bicycling, driving, moving around the house, walking outdoors, reading, watching television (TV), hobby or pastime, feel hindered.

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)	7.51 units on a scale Standard Error 2.646	21.67 units on a scale Standard Error 2.891

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo). A change from baseline of zero was imputed at the first postbaseline visit for participants with no postbaseline assessment.

The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of TED by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale. Transformed Appearance score is the sum of scores from the following 8 questions to a scale of 0 (worst health) to 100 (best health): feel appearance has changed, feel being stared at, feel people react unpleasantly, influence on self-confidence, feel socially isolated, influence on making friends, appear less often on photos, try to mask changes in appearance.

Outcome measures

Measure	Placebo n=45 Participants A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.	Teprotumumab n=42 Participants Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study.
Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)	6.60 units on a scale Standard Error 2.656	12.92 units on a scale Standard Error 2.836

Adverse Events

Safety Population: Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Safety Population: Teprotumumab

Serious events: 5 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Safety Population: Placebo n=44 participants at risk A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received.	Safety Population: Teprotumumab n=43 participants at risk Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received.
Eye disorders Optic neuropathy	2.3% 1/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	0.00% 0/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	2.3% 1/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Gastrointestinal disorders Inflammatory bowel disease	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	2.3% 1/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Infections and infestations Escherichia sepsis	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	2.3% 1/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Hashimoto's encephalopathy	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	2.3% 1/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Renal and urinary disorders Urinary retention	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	2.3% 1/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.

Other adverse events

Measure	Safety Population: Placebo n=44 participants at risk A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received.	Safety Population: Teprotumumab n=43 participants at risk Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants started treatment at a dose of 10 mg/kg. At Week 3, the dose was escalated to 20 mg/kg and kept constant for the remainder of the study. Safety Population: participants who received at least 1 dose of study treatment, grouped by treatment actually received.
Gastrointestinal disorders Diarrhoea	4.5% 2/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	11.6% 5/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Gastrointestinal disorders Nausea	9.1% 4/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	18.6% 8/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
General disorders Fatigue	13.6% 6/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Infections and infestations Upper respiratory tract infection	9.1% 4/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	0.00% 0/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Investigations Weight decreased	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Metabolism and nutrition disorders Hyperglycaemia	4.5% 2/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	11.6% 5/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	4.5% 2/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	18.6% 8/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Dizziness	9.1% 4/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	0.00% 0/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Dysgeusia	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Headache	4.5% 2/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Paraesthesia	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Nervous system disorders Somnolence	6.8% 3/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	0.00% 0/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Skin and subcutaneous tissue disorders Alopecia	4.5% 2/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.
Skin and subcutaneous tissue disorders Rash	9.1% 4/44 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.	7.0% 3/43 • Up to Week 72 Treatment emergent adverse events (TEAEs) are presented, defined as events with onset at the time of or following the start of treatment with study drug or an event starting before the start of treatment but increasing in severity following the start of treatment.

Additional Information

Julie Ball, Executive Director

Horizon Pharma USA, Inc.

Email: clinicaltrials@horizonpharma.com

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.
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