A Phase 2b Extension Study of Two Doses 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 study objective is to continue to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of linsitinib in subjects who were enrolled in the prior VGN-TED-301 through Week 24. These subjects include VGN-TED-301 Week 24 proptosis non-responders or subjects who relapse during the Follow-Up Period of VGN-TED-301.

Official Title
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A Multicenter, Extension Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Two Doses of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)

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

Intervention / Treatment
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* Drug: linsitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject who completed the 24-week double-mask period of VGN-TED-301 and are proptosis non-responders (< 2 mm reduction in proptosis in the study eye) at Week 24 of VGN-TED-301 study or proptosis responders at Week 24 who relapse during the Follow-Up period of VGN-TED-301 Subject has not received any treatment for TED since Week 24 of VGN-TED-301 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 Baseline. Every effort should be made to correct mild hypo- or hyperthyroidism promptly and maintain the euthyroid state for the duration of the clinical trial Does not require immediate ophthalmic surgery, radiotherapy to orbits or other ophthalmological intervention at the time of Baseline and is not planning for any such treatment during the course of the study Exclusion Criteria: The exclusion criteria of protocol VGN-TED-301 also apply to this extension study.

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 |
| --- | --- |
| 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 | Percentage of subjects with a ≥ 2 mm reduction of proptosis from baseline as determined by exophthalmometer | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Proptosis to Week 24 (Study Eye) | Change from baseline in reduction of proptosis from baseline as determined by exophthalmometer | 24 weeks | 
| Percentage of Subjects who are Overall Responders at Week 24 | Percentage of Subjects with a response of ≥ 2 mm reduction of proptosis at Week 24 as determined by exophthalmometer | 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 |