Linsitinib for Thyroid Eye Disease

Recruiting at 1 trial location

Overseen By Robin Schmidt

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Sling Therapeutics, Inc.

Disqualifiers: Diabetes, Hypertension, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called linsitinib for people with Thyroid Eye Disease (TED), a condition that can cause eye bulging and discomfort. Researchers aim to determine if different doses of linsitinib can safely reduce these symptoms, particularly for those who did not respond well in a previous study. This trial suits individuals who completed the earlier study, still experience eye symptoms, and have not received additional TED treatment since then. Participants should have their thyroid levels under control and not require eye surgery or other treatments during the trial. As a Phase 2 trial, this research measures how well linsitinib works in an initial, smaller group, offering a chance to contribute to important findings.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you must not have received any treatment for Thyroid Eye Disease since Week 24 of the previous study.

Is there any evidence suggesting that linsitinib is likely to be safe for humans?

Research has shown that linsitinib is generally well-tolerated. In one study on thyroid eye disease, linsitinib proved safe, with most participants not experiencing serious side effects. Another study on cancer treatments confirmed its safety with similar results. These findings suggest that linsitinib is likely safe for humans, though mild side effects might occur. Prospective participants should discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid eye disease?

Researchers are excited about Linsitinib for treating Thyroid Eye Disease because it targets a different pathway than current options. Most treatments focus on reducing inflammation or modulating the immune response, but Linsitinib is an IGF-1R inhibitor, which means it specifically blocks the insulin-like growth factor receptor involved in the disease's progression. This unique mechanism has the potential to more directly address the underlying causes of the condition. Additionally, with both high and low-dose options being explored, Linsitinib offers flexibility in treatment, potentially leading to tailored therapies that maximize benefits while minimizing side effects.

What evidence suggests that linsitinib might be an effective treatment for thyroid eye disease?

Research has shown that linsitinib, a type of medication, may help treat thyroid eye disease. Studies have found that linsitinib can prevent this disease from developing and worsening in animals. It works by slowing the growth of harmful cells and aiding in their elimination, which helps control the disease. Linsitinib also reduces swelling and discomfort around the eyes by lowering inflammation. Notably, it is the first pill to show significant results in managing thyroid eye disease. This trial will compare different doses of linsitinib, with one group receiving a high dose and another a low dose, to evaluate its effectiveness and safety. These findings suggest that linsitinib could be a strong option for people with this condition. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with active, moderate to severe Thyroid Eye Disease (TED) who participated in a previous study (VGN-TED-301) but didn't respond well or relapsed. They shouldn't have received any TED treatments since that study and must have their thyroid disease under control or only mildly off from normal levels.

Inclusion Criteria

My thyroid function is normal or slightly off but under control.

I completed 24 weeks of VGN-TED-301 without significant eye bulging reduction or my condition worsened after initial improvement.

I haven't had treatment for TED since Week 24 of VGN-TED-301.

Exclusion Criteria

The exclusion criteria of protocol VGN-TED-301 also apply to this extension study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a high or low dose of Linsitinib for the continuation of the study

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Linsitinib

Trial Overview The trial continues to test the effects of Linsitinib on patients with TED. It focuses on those who either did not respond adequately to previous treatment by Week 24 of the initial VGN-TED-301 study or had a relapse during its follow-up period.

How Is the Trial Designed?

Group I: High Dose Active Control 1 Intervention

Active Arm High Dose Linsitinib

Group II: Low Dose Active Control 1 Intervention

Active Arm Low Dose Linsitinib

Who Is Running the Clinical Trial?

Sling Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Teprotumumab (Tepro) effectively inhibits hyaluronan (HA) production in orbital fibroblasts from patients with thyroid eye disease (TED) by blocking the crosstalk between TSH receptors (TSHR) and IGF1 receptors (IGF1R), which is crucial for the disease's pathogenesis.

The study demonstrated that Tepro does not bind to TSHRs but still reduces HA production stimulated by TSHR/IGF1R crosstalk, indicating that its mechanism of action in treating TED involves disrupting this interaction rather than directly targeting TSHRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease. Krieger, CC., Sui, X., Kahaly, GJ., et al.[2022]

In a study of 17 patients with thyroid eye disease (TED), treatment with teprotumumab resulted in a significant reduction in intraocular pressure (IOP), with decreases of approximately 4.9 mm Hg at both 6 and 12 weeks after starting treatment.

The findings suggest that teprotumumab is effective in lowering IOP in TED patients, indicating its potential as a therapeutic option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of teprotumumab on intraocular pressure in thyroid-associated ophthalmopathy. Adetunji, MO., Nguyen, BJ., McGeehan, B., et al.[2022]

Teprotumumab, an IGF-1R inhibitor approved for thyroid eye disease (TED), has shown effectiveness in improving symptoms like proptosis and diplopia even in patients with long-standing disease or those who have not responded to previous treatments.

Recent reports suggest that teprotumumab can benefit patients regardless of disease duration or inflammation markers, indicating its potential as a versatile treatment option for TED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. Subramanian, PS., Cho, RI., Kahana, A.[2023]

Linsitinib, a dual kinase inhibitor, effectively prevented autoimmune hyperthyroidism in the early phase of Graves' disease by reducing T-cell infiltration and morphological changes associated with hyperthyroidism.

In the late phase of the disease, linsitinib significantly reduced immune cell infiltration in the orbit and improved tissue remodeling, indicating its potential as a novel treatment for thyroid eye disease associated with Graves' disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease. Gulbins, A., Horstmann, M., Daser, A., et al.[2023]

In a study of nine patients with chronic thyroid eye disease (TED) and low clinical activity scores, treatment with teprotumumab resulted in a significant average reduction of 4.0 mm in proptosis (eye bulging) immediately after treatment, indicating its efficacy.

Despite some reported side effects, such as myalgias and hair thinning, teprotumumab appears to be a promising treatment option for patients with chronic TED, as evidenced by sustained proptosis reduction observed in follow-up assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for chronic thyroid eye disease. Ozzello, DJ., Dallalzadeh, LO., Liu, CY.[2022]

Teprotumumab significantly reduces proptosis (eye bulging) and inflammation in patients with chronic Thyroid Eye Disease (TED), with an average reduction of 3.5 mm in proptosis after treatment.

In a study of 31 patients who received an average of 7 infusions, 67% of those with diplopia (double vision) experienced a significant improvement, and there was a notable reduction in both muscle and fat tissue volume in the orbits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. Ugradar, S., Kang, J., Kossler, AL., et al.[2022]

In a study of 156 patients with active, untreated thyroid eye disease, those aged 46-70 showed significantly higher clinical activity scores (CAS) compared to younger patients (18-45), indicating more severe symptoms.

Older patients (46-70 years) experienced more conjunctival redness and chemosis, which contributed to their higher CAS scores, suggesting that age may influence the severity of thyroid eye disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score. North, VS., Zhou, HW., Tran, AQ., et al.[2023]

Teprotumumab, an IGF-1R antagonist antibody, has shown efficacy and safety in treating moderate-to-severe thyroid eye disease (TED) in phase 2 and 3 clinical trials, leading to significant improvements in proptosis for patients.

This targeted therapy represents a shift in TED management, as it not only addresses symptoms but also modifies the disease course, potentially improving long-term patient outcomes compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Era in the Treatment of Thyroid Eye Disease. Patel, A., Yang, H., Douglas, RS.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05276063

A Phase 2b, Study of Linsitinib in Subjects With Active, ... The overall objective is to study the safety, pharmacokinetics and efficacy of linsitinib (a small molecule IGF-1R inhibitor) administered orally twice ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10331459/

Linsitinib, an IGF-1R inhibitor, attenuates disease ... Here, we demonstrate that linsitinib effectively prevents development and progression of thyroid eye disease in an experimental murine model for ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11668815/

Linsitinib inhibits proliferation and induces apoptosis of ... Linsitinib effectively induces apoptosis and inhibits proliferation of both IGF-1R and TSH-R expressing target cells, therefore demonstrating its therapeutic ...

4. slingtx.com slingtx.com/2025/01/14/sling-therapeutics-announces-positive-topline-results-from-phase-2b-3-lids-clinical-trial-of-oral-small-molecule-linsitinib-in-patients-with-thyroid-eye-disease/

Linsitinib is the first and only oral small molecule ... Linsitinib is the first and only oral small molecule therapy to establish statistical and clinical significance in Thyroid Eye Disease (TED).

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0311093

Linsitinib inhibits IGF-1-induced cell proliferation and ... It has been reported that linsitinib reduces infiltration of inflammatory cells in orbital tissues, resulting in the reduction of muscle edema ...

6. optometrytimes.com optometrytimes.com/view/sling-therapeutics-announces-topline-efficacy-safety-data-from-phase-2b-3-lids-trial-on-linsitinib-in-patients-with-ted

Sling Therapeutics announces topline efficacy, safety data ... The trial met its primary endpoint with statistical significance for the 150mg BID dose, with a proptosis responder rate of 52% (p=0.01).

7. healio.com healio.com/news/ophthalmology/20250116/linsitinib-for-thyroid-eye-disease-shows-proptosis-reduction-safety-in-phase-2b3-trial

Linsitinib for thyroid eye disease shows proptosis reduction ... The trial achieved its primary endpoint of proptosis reduction at week 24 with a statistically significant proptosis responder rate of 52% in ...

8. ophthalmologymanagement.com ophthalmologymanagement.com/news/2025/sling-therapeutics-announces-positive-topline-results-from-phase-2b3-lids-clinical-trial-of-oral-small-molecule-linsitinib-in-patients-with-ted/

Sling Therapeutics Announces Positive Topline Results ... Linsitinib in this trial validated the safety profile seen in the prior oncology studies and demonstrated a favorable safety profile on key ...