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

August 7, 2026 updated by: Sling Therapeutics, Inc.

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)

The goal of this clinical trial is to evaluate the efficacy, safety, and tolerability of linsitinib in participants with moderate to severe Thyroid Eye Disease (TED).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Nevada
      • Las Vegas, Nevada, United States, 89144
        • Recruiting
        • Advancing Research International

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double-mask Treatment Arm
Participants receive linsitinib 150 mg twice daily for 24 weeks.
Drug: linsitinib
150 mg linsitinib is taken twice daily by mouth for 24 weeks
Placebo Comparator: Double-mask Placebo Arm
Participants receive placebo 0 mg twice daily for 24 weeks.
Drug: Placebo
0 mg placebo taken twice daily by mouth for 24 weeks
Experimental: Open-label Extension Treatment Arm
Proptosis non-responders/relapsed proptosis responders receive linsitinib 150 mg twice daily for 24 weeks.
Drug: linsitinib
150 mg linsitinib is taken twice daily by mouth for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure percentage of participants who are Proptosis Responders at Week 24
Time Frame: 24 weeks
The proptosis responder rate is the percentage of participants with a ≥ 2 mm reduction of proptosis from Baseline in the primary study eye without deterioration (≥ 2 mm increase) of proptosis in the contralateral non-study eye.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change from Baseline in Proptosis to Week 24
Time Frame: 24 Weeks
Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the mean change from Baseline to Week 24 in proptosis measurement in the primary study eye.
24 Weeks
Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the overall responder rate at Week 24
Time Frame: 24 Weeks
Overall responder rate (percentage of participants with ≥ 2-point reduction in 7 point CAS and ≥ 2 mm reduction in proptosis from Baseline in the primary study eye), provided there is no corresponding deterioration (≥ 2-point/mm increase) in CAS or proptosis in the contralateral non-study eye at Week 24.
24 Weeks
Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the percentage of participants with a CAS value of 0 or 1 at Week 24 in the primary study eye.
Time Frame: 24 Weeks
Percentage of participants with a CAS value of 0 or 1 at Week 24 in the primary study eye.
24 Weeks
Evaluate the effect of linsitinib 150 mg twice daily versus placebo on the mean change from Baseline to Week 24 in the GO-QoL questionnaire overall score.
Time Frame: 24 Weeks
Mean change from Baseline to Week 24 in the Graves' Orbitopathy Quality of Life questionnaire (GO-QoL) questionnaire overall score (0-100 where higher scores are a better outcome).
24 Weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the safety and tolerability of linsitinib 150 mg twice daily as compared to placebo over a 24-week period.
Time Frame: 24 Weeks
Incidence of TEAEs (defined as AEs that begin or worsen after the first dose of study drug), treatment-emergent SAEs, deaths, discontinuation due to AEs, clinical safety laboratory results, vital signs, physical and ophthalmic examinations, and ECG parameters.
24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sling Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 4, 2026

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 28, 2030

Study Registration Dates

First Submitted

August 3, 2026

First Submitted That Met QC Criteria

August 3, 2026

First Posted (Actual)

August 7, 2026

Study Record Updates

Last Update Posted (Actual)

August 11, 2026

Last Update Submitted That Met QC Criteria

August 7, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SLG-TED-303

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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