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

Phase 2

Active, not recruiting

• Conditions: Thyroid Eye Disease; Orbital Diseases; Exophthalmos; Thyroid Associated Ophthalmopathy; Graves Orbitopathy; Endocrine System Diseases; Thyroid Diseases; IGF1R; Eye Diseases; Graves Ophthalmopathy
• Interventions: Drug: Placebo; Drug: Linsitinib

• Registration Number: NCT05276063
• Lead Sponsor: Sling Therapeutics, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-02
• Study First Submitted QC: 2022-03-02
• Study First Posted: 2022-03-11
• Study Start: 2022-07-01
• Primary Completion: 2024-10-15
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Arm
Low Dose	Linsitinib	Active Arm Low Dose Linsitinib
High Dose	Linsitinib	Active Arm High Dose Linsitinib

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects who are Proptosis Responders at Week 24	24 weeks

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Proptosis to Week 24 (Study Eye)	24 weeks
Percentage of Subjects who are Overall Responders at Week 24	24 weeks
Percentage of Subjects who are Diplopia 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

Trial Locations

Locations (30)

Bascom Palmer Eye Institute; 🇺🇸 Miami, Florida, United States

Sarasota Retina Institute; 🇺🇸 Sarasota, Florida, United States

Mass Eye and Ear; 🇺🇸 Boston, Massachusetts, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Thrive Health Research; 🇺🇸 Beverly Hills, California, United States

UC San Diego Health; 🇺🇸 La Jolla, California, United States

Byers Eye Institute - Stanford University; 🇺🇸 Palo Alto, California, United States

Center for Excellence in Eye Care; 🇺🇸 Miami, Florida, United States

Chicago Oculofacial Plastic Surgery; 🇺🇸 Chicago, Illinois, United States

Wolfe Eye Clinic; 🇺🇸 West Des Moines, Iowa, United States

Washington University in St. Louis/Barnes Jewish Hospital; 🇺🇸 Creve Coeur, Missouri, United States

Columbia University; 🇺🇸 New York, New York, United States

Neuro-Eye Clinical Trials, Inc.; 🇺🇸 Bellaire, Texas, United States

Hospital Universitari de Bellvitge; 🇪🇸 Barcelona, Spain

Hospital La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Frimley Health Foundation Trust; 🇬🇧 Camberley, United Kingdom

Cardiff University; 🇬🇧 Cardiff, United Kingdom

Moorfields Eye Hospital NIHR Clinical Research Facility; 🇬🇧 London, United Kingdom

Vancouver Coastal Health Eye Care Center; 🇨🇦 Vancouver, British Columbia, Canada

West Virginia University Eye Institute; 🇺🇸 Morgantown, West Virginia, United States

Kahana Oculoplastic & Orbital Surgery; 🇺🇸 Livonia, Michigan, United States

University of Pisa; 🇮🇹 Pisa, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Endocrinology Pawilione Zonda; 🇮🇹 Milan, Italy

AOU Pisana; 🇮🇹 Pisa, Italy

Toronto Retina Institute; 🇨🇦 North York, Canada

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Eyelid Center of Utah; 🇺🇸 Salt Lake City, Utah, United States

Wake Forest Baptist Health Eye Center; 🇺🇸 Winston-Salem, North Carolina, United States

Kellogg Eye Center; 🇺🇸 Ann Arbor, Michigan, United States