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

NCT05276063 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: VGN-TED-301
• Study Type: interventional
• Target: 90
• Locations: 5 countries
• Sites: 30

Brief 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).

Conditions

Thyroid Eye Disease; Graves Orbitopathy; Endocrine System Diseases; Eye Diseases; Thyroid Associated Ophthalmopathy; Graves Ophthalmopathy; Thyroid Diseases; Orbital Diseases; Proptosis; IGF1R; Exophthalmos; Hashimoto

Keywords

Thyroid Associated Ophthalmopathies

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects who are Proptosis Responders at Week 24

  24 weeks

Secondary Outcomes (5)

• Change from Baseline in Proptosis to Week 24 (Study Eye)

  24 weeks

• Percentage of Subjects who are Diplopia Responders at Week 24

  24 weeks

• Percentage of Subjects who are Overall Responders at Week 24

  24 weeks

• Percentage of Subjects who are CAS Categorical Responders at Week 24 (Study Eye)

  24 weeks

• Change from Baseline in the Graves' Ophthalmopathy Quality of Life (GO-QoL) Questionnaire Overall Score to Week 24.

  24 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo Arm

Drug: Placebo

Low Dose

ACTIVE COMPARATOR

Active Arm Low Dose Linsitinib

Drug: Linsitinib

High Dose

ACTIVE COMPARATOR

Active Arm High Dose Linsitinib

Drug: Linsitinib

Interventions

Linsitinib DRUG

Study medication taken twice daily by mouth

High Dose; Low Dose

Placebo DRUG

Placebo taken twice daily by mouth

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sling Therapeutics, Inc.: lead

Study Sites (30)

Thrive Health Research

Beverly Hills, California, 90210, United States

Location

UC San Diego Health

La Jolla, California, 92093, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Byers Eye Institute - Stanford University

Palo Alto, California, 94303, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Center for Excellence in Eye Care

Miami, Florida, 33176, United States

Location

Sarasota Retina Institute

Sarasota, Florida, 34239, United States

Location

Chicago Oculofacial Plastic Surgery

Chicago, Illinois, 60614, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Mass Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Kahana Oculoplastic & Orbital Surgery

Livonia, Michigan, 48152, United States

Location

Washington University in St. Louis/Barnes Jewish Hospital

Creve Coeur, Missouri, 63141, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Forest Baptist Health Eye Center

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Neuro-Eye Clinical Trials, Inc.

Bellaire, Texas, 77401, United States

Location

Eyelid Center of Utah

Salt Lake City, Utah, 84102, United States

Location

West Virginia University Eye Institute

Morgantown, West Virginia, 26506, United States

Location

Vancouver Coastal Health Eye Care Center

Vancouver, British Columbia, V5Z 3N9, Canada

Location

Toronto Retina Institute

North York, M3C 0G9, Canada

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda

Milan, Italy

Location

AOU Pisana

Pisa, Italy

Location

University of Pisa

Pisa, Italy

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Frimley Health Foundation Trust

Camberley, GU16 7UJ, United Kingdom

Location

Cardiff University

Cardiff, CF14 4XN, United Kingdom

Location

Moorfields Eye Hospital NIHR Clinical Research Facility

London, EC1V 2PD, United Kingdom

Location

MeSH Terms

Conditions

Graves Ophthalmopathy; Endocrine System Diseases; Eye Diseases; Thyroid Diseases; Orbital Diseases; Exophthalmos; Hashimoto Disease

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Graves Disease; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Thyroiditis, Autoimmune; Thyroiditis

Study Design

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

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: March 11, 2022
• Study Start: July 1, 2022
• Primary Completion: October 15, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Proposals should be directed to info@slingtx.com

Locations

ES (3); GB (3); CA (2); US (19); IT (3)