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

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)

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).

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Endocrine System Diseases; Thyroid Diseases; Thyroid Eye Disease; Graves Ophthalmopathy; Exophthalmos; Orbital Diseases; Thyroid Associated Ophthalmopathy; Graves Orbitopathy; Proptosis; IGF1R; Hashimoto
• Intervention / Treatment: Drug: Placebo; Drug: Linsitinib

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • North York, Canada, M3C 0G9
    • Toronto Retina Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
      • Vancouver Coastal Health Eye Care Center
• Italy
  • Milan, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda
  • Pisa, Italy
    • AOU Pisana
  • Pisa, Italy
    • University of Pisa
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28006
    • Hospital La Princesa
• United Kingdom
  • Camberley, United Kingdom, GU16 7UJ
    • Frimley Health Foundation Trust
  • Cardiff, United Kingdom, CF14 4XN
    • Cardiff University
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NIHR Clinical Research Facility
• United States
  • California
    • Beverly Hills, California, United States, 90210
      • Thrive Health Research
    • La Jolla, California, United States, 92093
      • UC San Diego Health
    • Los Angeles, California, United States, 90095
      • UCLA
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute - Stanford University
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
    • Miami, Florida, United States, 33176
      • Center for Excellence in Eye Care
    • Sarasota, Florida, United States, 34239
      • Sarasota Retina Institute
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Chicago Oculofacial Plastic Surgery
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Wolfe Eye Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mass Eye and Ear
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Kellogg Eye Center
    • Livonia, Michigan, United States, 48152
      • Kahana Oculoplastic & Orbital Surgery
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Washington University in St. Louis/Barnes Jewish Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Eye Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Bellaire, Texas, United States, 77401
      • Neuro-Eye Clinical Trials, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Eyelid Center of Utah
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Arm	Drug: Placebo; Placebo taken twice daily by mouth
Active Comparator: Low Dose; Active Arm Low Dose Linsitinib	Drug: Linsitinib; Study medication taken twice daily by mouth
Active Comparator: High Dose; Active Arm High Dose Linsitinib	Drug: Linsitinib; Study medication taken twice daily by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Are Proptosis Responders at Week 24	Proptosis response is defined as a ≥ 2 mm reduction from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Are Overall Responders at Week 24	Overall response is defined as a >= 2-point reduction from baseline CAS and >= 2 mm reduction in proptosis in the primary study eye at week 24 without deterioration (>= 2-point increase) in CAS or deterioration (>= 2 mm increase) of proptosis in the contralateral non-study eye. In the event of death, the latest CAS/proptosis observations will be carried forward. Missing values of CAS and proptosis measurement in the primary study eye and contralateral non-study eye at week 24 are multiple imputed by using all available prior CAS/proptosis measures, smoking status and treatment group.	24 weeks
Percentage of Subjects With a CAS Value of 0 or 1 at Week 24	A CAS value of 0 or 1 in primary study eye at week 24. In the event of death, the latest CAS observation will be carried forward. Missing values of CAS at week 24 are multiple imputed by using all available prior CAS measures, smoking status and treatment group	24 weeks
Change From Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.	Change from baseline to week 24 in Graves' Ophthalmology Quality of Life (GO-QoL) overall score or to last assessed value in case of death. Missing values of GO-QoL overall score up to week 24 are multiple imputed by using all available prior GO-QoL overall score measures, smoking status and treatment group. Overall scale was measured from 0 minimum to 100 maximum (0 is worse health state and 100 is best health state)	24 weeks

Collaborators and Investigators

• Sponsor: Sling Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): October 15, 2024
• Study Completion (Actual): September 26, 2025

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Thyroid Associated Ophthalmopathies
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Graves Disease; Goiter; Hyperthyroidism; Thyroiditis, Autoimmune; Thyroiditis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thyroid Diseases; Eye Diseases; Graves Ophthalmopathy; Endocrine System Diseases; Hashimoto Disease; Orbital Diseases; Exophthalmos; 3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol
• Other Study ID Numbers: VGN-TED-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data collected during the trial, after deidentification will be made available.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Proposals should be directed to info@slingtx.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No