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

NCT01868997 | Completed Phase 2 Results DMC

• 3 other identifiers: TED01RVFD004792-01A12014-000113-31
• Study Type: interventional
• Target: 88
• Locations: 4 countries
• Sites: 15

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"

Conditions

Thyroid Associated Ophthalmopathies; Thyroid-Associated Ophthalmopathy

Keywords

Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated; Ophthalmopathy

Outcome Measures

Primary Outcomes (1)

• Responder Status at 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.

  Week 24

Secondary Outcomes (5)

• Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])

  Baseline to Week 24

• Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)

  Baseline to Week 24

• Overall Average Change From Baseline in CAS to Week 24 (MMRM)

  Baseline to Week 24

• Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)

  Baseline to Week 24

• Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)

  Baseline to Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

A placebo infusion (normal saline) administered q3W by IV infusion over a period of 24 weeks for a total of 8 infusions.

Drug: normal saline

Teprotumumab

EXPERIMENTAL

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.

Drug: teprotumumab

Interventions

teprotumumab DRUG

Also known as: RV 001, HZN-001

Teprotumumab

normal saline DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (15)

Jules Stein Eye Institute at UCLA

Los Angeles, California, 90095, United States

Location

University of Denver

Aurora, Colorado, 80045, United States

Location

Emory University Department of Ophthalmology

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics, Department of Ophthalmology

Iowa City, Iowa, 52242, United States

Location

Kellogg Eye Center at University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Washington University Department of Ophthalmology

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center Department of Ophthalmology

Omaha, Nebraska, 68198, United States

Location

Casey Eye Institute at Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hamilton Eye Institute at University of Tennessee

Memphis, Tennessee, 38163, United States

Location

Eye Wellness Center

Houston, Texas, 77005, United States

Location

Medical College of Wisconsin, The Eye Institute

Milwaukee, Wisconsin, 53226, United States

Location

Johannes Gutenberg University Medical Center

Mainz, 55101, Germany

Location

Fondazione Ca' Granda Ospedale Policlinico Graves GO Center

Milan, 20122, Italy

Location

University of Pisa, Azienda Ospedaliera

Pisa, 56100, Italy

Location

Moorfields Eye Hospital

London, United Kingdom

Location

Related Publications (3)

• Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.

  PMID: 28467880 RESULT

• Xin Y, Xu F, Gao Y, Bhatt N, Chamberlain J, Sile S, Hammel S, Holt RJ, Ramanathan S. Pharmacokinetics and Exposure-Response Relationship of Teprotumumab, an Insulin-Like Growth Factor-1 Receptor-Blocking Antibody, in Thyroid Eye Disease. Clin Pharmacokinet. 2021 Aug;60(8):1029-1040. doi: 10.1007/s40262-021-01003-3. Epub 2021 Mar 26.

  PMID: 33768488 DERIVED

• Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014 Mar 20;55(3):1735-48. doi: 10.1167/iovs.14-14002.

  PMID: 24651704 DERIVED

MeSH Terms

Conditions

Graves Ophthalmopathy; Eye Diseases

Interventions

teprotumumab; Saline Solution

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Julie Ball, Executive Director
• Organization: Horizon Pharma USA, Inc.

clinicaltrials@horizonpharma.com

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: June 5, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: February 22, 2017
• Last Updated: December 17, 2024
• Results First Posted: August 30, 2017

Record last verified: 2024-12

Locations

IT (2); GB (1); DE (1); US (11)