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

Sponsor

Sling Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05276063

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

8.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Thyroid Eye Disease Graves Orbitopathy Endocrine System Diseases Eye Diseases Thyroid Associated Ophthalmopathy Graves Ophthalmopathy Thyroid Diseases Orbital Diseases Proptosis IGF1R Exophthalmos Hashimoto	Drug: Linsitinib Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percentage of Subjects who are Proptosis Responders at Week 24 [24 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (defined as normal TSH) or, have subclinical hyperthyroidism (defined as normal FT4 and FT3 with TSH below the normal range).
Does not require immediate surgery, radiotherapy 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 surgery.
Any steroid 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
2	Sarasota Retina Institute	Sarasota	Florida	United States	34239
3	Oregon Health and Science University	Portland	Oregon	United States	97239
4	Neuro-Eye Clinical Trials, Inc.	Bellaire	Texas	United States	77401
5	Eyelid Center of Utah	Salt Lake City	Utah	United States	84102
6	West Virginia University Eye Institute	Morgantown	West Virginia	United States	26506
7	University of Wisconsin	Madison	Wisconsin	United States	57305
8	Toronto Retina Institute	North York		Canada	M3C 0G9
9	Moorfields Eye Hospital NIHR Clinical Research Facility	London		United Kingdom	EC1V 2PD