Clinical trial NCT01868997: Teprotumumab (RV 001) Treatment in Patients With Active Thyroid Eye Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Associated Ophthalmopathies
Thyroid-Associated Ophthalmopathy
Keywords: Thyroid Eye Disease, Graves Orbitopathy, Thyroid Associated
Ophthalmopathy
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-06-05
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: Study with completed results acquired from Horizon in 2024.

Eligibility criteria: 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

Primary outcomes:
measure: Responder Status at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Overall Average Change From Baseline in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale - Overall to Week 24 (Mixed-Model Repeated Measures [MMRM])
timeFrame: Baseline to Week 24
measure: Overall Average Change From Baseline in Proptosis of the Study Eye to Week 24 (MMRM)
timeFrame: Baseline to Week 24
measure: Overall Average Change From Baseline in CAS to Week 24 (MMRM)
timeFrame: Baseline to Week 24
measure: Overall Average Change From Baseline in GO-QOL Scale - Visual Functioning to Week 24 (MMRM)
timeFrame: Baseline to Week 24
measure: Overall Average Change From Baseline in GO-QOL Scale - Appearance to Week 24 (MMRM)
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute at UCLA
state: California
city: Aurora
country: United States
facility: University of Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University Department of Ophthalmology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics, Department of Ophthalmology
state: Iowa
city: Ann Arbor
country: United States
facility: Kellogg Eye Center at University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Department of Ophthalmology
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center Department of Ophthalmology
state: Nebraska
city: Portland
country: United States
facility: Casey Eye Institute at Oregon Health and Science University
state: Oregon
city: Memphis
country: United States
facility: Hamilton Eye Institute at University of Tennessee
state: Tennessee
city: Houston
country: United States
facility: Eye Wellness Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, The Eye Institute
state: Wisconsin
city: Mainz
country: Germany
facility: Johannes Gutenberg University Medical Center
city: Milan
country: Italy
facility: Fondazione Ca' Granda Ospedale Policlinico Graves GO Center
city: Pisa
country: Italy
facility: University of Pisa, Azienda Ospedaliera
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.