A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)

Eye Diseases Clinical Trial

— LIDS  

Official title:

A Phase 2b, Randomized, Double-Mask, Placebo-Controlled, Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05276063
• Other study ID #: VGN-TED-301
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: July 1, 2022
• Est. completion date: September 2026

Study information

• Verified date: May 2024
• Source: Sling Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice daily (BID) vs. placebo, at 24 weeks in the treatment of subjects with active, moderate to severe thyroid eye disease (TED).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: September 2026
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of Graves' Disease and/or autoimmune Hashimoto's thyroiditis associated with active moderate to severe TED with a CAS = 4 (on the 7- item scale) for the most severely affected eye (primary study eye) at Screening and Baseline

• Confirmed active TED (not sight-threatening but has an appreciable impact on daily life, with onset (as determined by patient records) within 12 months prior to the Baseline visit and usually associated with one or more of the following: lid retraction = 2 mm, moderate or severe soft tissue involvement, exophthalmos = 3 mm above normal for race and gender, and/or inconstant or constant diplopia.

• Subjects must be euthyroid with the participant's baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine levels [FT3] < 50% above or below the normal limits) at Screening.

• Does not require immediate ophthalmic surgery, radiotherapy to orbits or other ophthalmological intervention at the time of Screening and is not planning for any such treatment during the course of the study.

Exclusion Criteria:

• Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months.

• Corneal decompensation unresponsive to medical management.

• Previous orbital irradiation or orbital surgery.

• Any glucocorticoid use (intravenous [IV] or oral) with a cumulative dose equivalent to >= 1g of methylprednisolone or equivalent for the treatment of TED within 3 months of Screening.

• Prior IGF-1R inhibitor therapy for any condition.

Related Conditions & MeSH terms

• Endocrine System Diseases
• Exophthalmos
• Eye Diseases
• Graves Ophthalmopathy
• Graves Orbitopathy
• Hashimoto
• Orbital Diseases
• Thyroid Associated Ophthalmopathy
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• Linsitinib
Study medication taken twice daily by mouth
• Placebo
Placebo taken twice daily by mouth

Locations

Country	Name	City	State
Canada	Toronto Retina Institute	North York
Canada	Vancouver Coastal Health Eye Care Center	Vancouver	British Columbia
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda	Milan
Italy	AOU Pisana	Pisa
Italy	University of Pisa	Pisa
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital La Princesa	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
United Kingdom	Frimley Health Foundation Trust	Camberley
United Kingdom	Cardiff University	Cardiff
United Kingdom	Moorfields Eye Hospital NIHR Clinical Research Facility	London
United States	Kellogg Eye Center	Ann Arbor	Michigan
United States	Neuro-Eye Clinical Trials, Inc.	Bellaire	Texas
United States	Thrive Health Research	Beverly Hills	California
United States	Mass Eye and Ear	Boston	Massachusetts
United States	Chicago Oculofacial Plastic Surgery	Chicago	Illinois
United States	Washington University in St. Louis/Barnes Jewish Hospital	Creve Coeur	Missouri
United States	UC San Diego Health	La Jolla	California
United States	Kahana Oculoplastic & Orbital Surgery	Livonia	Michigan
United States	UCLA	Los Angeles	California
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Center for Excellence in Eye Care	Miami	Florida
United States	West Virginia University Eye Institute	Morgantown	West Virginia
United States	Columbia University	New York	New York
United States	Byers Eye Institute - Stanford University	Palo Alto	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Eyelid Center of Utah	Salt Lake City	Utah
United States	Sarasota Retina Institute	Sarasota	Florida
United States	Wolfe Eye Clinic	West Des Moines	Iowa
United States	Wake Forest Baptist Health Eye Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sling Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects who are Proptosis Responders at Week 24		24 weeks
Secondary	Change from Baseline in Proptosis to Week 24 (Study Eye)		24 weeks
Secondary	Percentage of Subjects who are Diplopia Responders at Week 24		24 weeks
Secondary	Percentage of Subjects who are Overall Responders at Week 24		24 weeks
Secondary	Percentage of Subjects who are CAS Categorical Responders at Week 24 (Study Eye)		24 weeks
Secondary	Change from Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.		24 weeks