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Trial record 7 of 44 for:    eye diseases AND university of iowa

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

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ClinicalTrials.gov Identifier: NCT01868997
Recruitment Status : Completed
First Posted : June 5, 2013
Results First Posted : August 30, 2017
Last Update Posted : April 25, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Thyroid Associated Ophthalmopathies
Thyroid-Associated Ophthalmopathy
Interventions Drug: teprotumumab
Drug: normal saline
Enrollment 88

Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description 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 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.
Period Title: Overall Study
Started 45 [1] 42 [1]
Completed 38 36
Not Completed 7 6
Reason Not Completed
Adverse Event             2             5
Lack of Efficacy             2             0
Not Specified             3             1
[1]
randomized and treated
Arm/Group Title Placebo Teprotumumab Total
Hide Arm/Group Description A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. 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 of all reporting groups
Overall Number of Baseline Participants 45 42 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 42 participants 87 participants
54.1  (12.87) 51.7  (10.78) 52.9  (11.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 42 participants 87 participants
Female
36
  80.0%
28
  66.7%
64
  73.6%
Male
9
  20.0%
14
  33.3%
23
  26.4%
1.Primary Outcome
Title Responder Status at Week 24
Hide Description 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.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Population: all participants who were randomized to treatment and received at least 1 dose of medication (either teprotumumab or placebo).
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
9
  20.0%
29
  69.0%
Non-Responder / Missing
36
  80.0%
13
  31.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments Odds ratio, 95% confidence interval, and P-value are obtained from a logistic regression model with treatment and smoking status as covariates.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.86
Confidence Interval (2-Sided) 95%
3.293 to 23.825
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Average Change From Baseline in Graves’ Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])
Hide Description 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).
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.77  (2.251) 17.74  (2.423)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed-Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 10.97
Confidence Interval (2-Sided) 95%
4.561 to 17.375
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.221
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)
Hide Description 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.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Least Squares Mean (Standard Error)
Unit of Measure: mm
-0.15  (0.188) -2.46  (0.200)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed-Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value -2.31
Confidence Interval (2-Sided) 95%
-2.843 to -1.772
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.269
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Average Change From Baseline in CAS to Week 24 (MMRM)
Hide Description 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.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.85  (0.172) -3.43  (0.181)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed-Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value -1.59
Confidence Interval (2-Sided) 95%
-2.073 to -1.098
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.245
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)
Hide Description 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.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.51  (2.646) 21.67  (2.891)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Mixed-Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 14.16
Confidence Interval (2-Sided) 95%
6.549 to 21.773
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.827
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)
Hide Description 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.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Teprotumumab
Hide Arm/Group Description:
A placebo infusion (normal saline) was administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
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 Number of Participants Analyzed 45 42
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.60  (2.656) 12.92  (2.836)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Teprotumumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.101
Comments [Not Specified]
Method Mixed-Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean
Estimated Value 6.32
Confidence Interval (2-Sided) 95%
-1.255 to 13.901
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.810
Estimation Comments [Not Specified]
Time Frame Up to Week 72
Adverse Event Reporting Description 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.
 
Arm/Group Title Safety Population: Placebo Safety Population: Teprotumumab
Hide Arm/Group Description

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.

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.

All-Cause Mortality
Safety Population: Placebo Safety Population: Teprotumumab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/43 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Safety Population: Placebo Safety Population: Teprotumumab
Affected / at Risk (%) Affected / at Risk (%)
Total   1/44 (2.27%)   5/43 (11.63%) 
Eye disorders     
Optic neuropathy  1  1/44 (2.27%)  0/43 (0.00%) 
Gastrointestinal disorders     
Diarrhea  1  0/44 (0.00%)  1/43 (2.33%) 
Inflammatory bowel disease  1  0/44 (0.00%)  1/43 (2.33%) 
Infections and infestations     
Escherichia sepsis  1  0/44 (0.00%)  1/43 (2.33%) 
Nervous system disorders     
Hashimoto's encephalopathy  1  0/44 (0.00%)  1/43 (2.33%) 
Renal and urinary disorders     
Urinary retention  1  0/44 (0.00%)  1/43 (2.33%) 
1
Term from vocabulary, MedDRA 14.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Safety Population: Placebo Safety Population: Teprotumumab
Affected / at Risk (%) Affected / at Risk (%)
Total   21/44 (47.73%)   25/43 (58.14%) 
Gastrointestinal disorders     
Diarrhoea  1  2/44 (4.55%)  5/43 (11.63%) 
Nausea  1  4/44 (9.09%)  8/43 (18.60%) 
General disorders     
Fatigue  1  6/44 (13.64%)  3/43 (6.98%) 
Infections and infestations     
Upper respiratory tract infection  1  4/44 (9.09%)  0/43 (0.00%) 
Investigations     
Weight decreased  1  0/44 (0.00%)  3/43 (6.98%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  2/44 (4.55%)  5/43 (11.63%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  2/44 (4.55%)  8/43 (18.60%) 
Nervous system disorders     
Dizziness  1  4/44 (9.09%)  0/43 (0.00%) 
Dysgeusia  1  0/44 (0.00%)  3/43 (6.98%) 
Headache  1  2/44 (4.55%)  3/43 (6.98%) 
Paraesthesia  1  0/44 (0.00%)  3/43 (6.98%) 
Somnolence  1  3/44 (6.82%)  0/43 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  2/44 (4.55%)  3/43 (6.98%) 
Dry skin  1  0/44 (0.00%)  3/43 (6.98%) 
Rash  1  4/44 (9.09%)  3/43 (6.98%) 
1
Term from vocabulary, MedDRA 14.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Julie Ball, Executive Director
Organization: Horizon Pharma USA, Inc.
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT01868997     History of Changes
Other Study ID Numbers: TED01RV
FD004792-01A1 ( Other Identifier: FDA - Office of Orphan Product Development (OOPD) )
2014-000113-31 ( EudraCT Number )
First Submitted: May 2, 2013
First Posted: June 5, 2013
Results First Submitted: August 10, 2017
Results First Posted: August 30, 2017
Last Update Posted: April 25, 2018