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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.

Tracking Information
First Submitted Date  ICMJE May 2, 2013
First Posted Date  ICMJE June 5, 2013
Results First Submitted Date  ICMJE August 10, 2017
Results First Posted Date  ICMJE August 30, 2017
Last Update Posted Date April 25, 2018
Actual Study Start Date  ICMJE July 2013
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
Responder Status at Week 24 [ Time Frame: Week 24 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
Clinical Activity Score [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT01868997 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
  • Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM]) [ Time Frame: Baseline to Week 24 ]
    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).
  • Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM) [ Time Frame: Baseline to Week 24 ]
    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.
  • Overall Average Change From Baseline in CAS to Week 24 (MMRM) [ Time Frame: Baseline to Week 24 ]
    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.
  • Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM) [ Time Frame: Baseline to Week 24 ]
    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.
  • Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM) [ Time Frame: Baseline to Week 24 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2013)
Clinical Severity Score [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
Official Title  ICMJE A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study Of RV 001, An Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (q3W) By Intravenous (IV) Infusion In Patients Suffering From Active Thyroid Eye Disease (TED)
Brief Summary

The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED.

"Funding Source - FDA OOPD"

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Thyroid Associated Ophthalmopathies
  • Thyroid-Associated Ophthalmopathy
Intervention  ICMJE
  • Drug: teprotumumab
    Other Names:
    • RV 001
    • HZN-001
  • Drug: normal saline
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.
    Intervention: Drug: normal saline
  • Experimental: Teprotumumab
    Teprotumumab administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions. All participants start treatment at a dose of 10 mg/kg. At Week 3, the dose is escalated to 20 mg/kg and kept constant for the remainder of the study.
    Intervention: Drug: teprotumumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2017)
88
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2013)
84
Actual Study Completion Date  ICMJE February 22, 2017
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
  • Fewer than 9 months from onset of TED
  • No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
  • Euthyroid or with mild hypo or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits (every effort should be made to correct the mild hypo- or hyperthyroidism promptly)

Exclusion Criteria:

  • Optic neuropathy
  • Corneal decompensation unresponsive to medical management
  • Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
  • Poorly controlled diabetes
  • Platelets < 100 x 10^9/L
  • Hemoglobin concentration > 2 g/dL below the lower limit of normal
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01868997
Other Study ID Numbers  ICMJE TED01RV
FD004792-01A1 ( Other Identifier: FDA - Office of Orphan Product Development (OOPD) )
2014-000113-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Horizon Pharma USA, Inc.
Study Sponsor  ICMJE Horizon Pharma USA, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Raymond S Douglas, MD, PhD Cedars-Sinai Medical Center
PRS Account Horizon Pharma USA, Inc.
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP