Study to Assess Linsitinib in Participants With Moderate to Severe Active Thyroid Eye Disease (TED)

A Phase 3, Randomized, Double-mask, Placebo-controlled Study With Open-label Extension to Evaluate the Efficacy and Safety of Linsitinib in Participants With Moderate to Severe Active Thyroid Eye Disease (TED)

Inclusion Criteria:

1. Participants must be ≥ 18 years of age at Screening
2. Clinical diagnosis of Graves' Disease and/or autoimmune Hashimoto's thyroiditis associated with active moderate to severe TED with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye (primary study eye) at Screening and Baseline.
3. Moderate to severe active TED (not sight-threatening but has an appreciable impact on daily life), with diagnosis of TED within 15 months prior to the Screening visit and usually associated with 1 or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, proptosis ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
4. Participants 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 of the central laboratory) at Screening.
5. 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:

1. Any progressing optic neuropathy due to TED that has worsened in the last 6 months in the opinion of the investigator.
2. Corneal decompensation unresponsive to medical management.
3. Previous orbital irradiation or orbital surgery in either eye.
4. Any glucocorticoid use (IV or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone or equivalent for the treatment of TED within 8 weeks of Screening.
5. Prior IGF-1R inhibitor therapy for any condition.

150 mg linsitinib is taken twice daily by mouth for 24 weeks

0 mg placebo taken twice daily by mouth for 24 weeks

Participants receive linsitinib 150 mg twice daily for 24 weeks.

Participants receive placebo 0 mg twice daily for 24 weeks.

Proptosis non-responders/relapsed proptosis responders receive linsitinib 150 mg twice daily for 24 weeks.