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

Study Overview
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Brief Summary
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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).

Official Title
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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)

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

Intervention / Treatment
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* Drug: Linsitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Arm | Drug: Placebo<br>* Placebo taken twice daily by mouth<br>|
| Active Comparator: Low Dose<br>Active Arm Low Dose Linsitinib | Drug: Linsitinib<br>* Study medication taken twice daily by mouth<br>|
| Active Comparator: High Dose<br>Active Arm High Dose Linsitinib | Drug: Linsitinib<br>* Study medication taken twice daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects who are Proptosis Responders at Week 24 |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid Associated Ophthalmopathies