Linsitinib for Thyroid Eye Disease

(LIDS Trial)

Not currently recruiting at 35 trial locations

Overseen By Cathy Radovich

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: VasaraGen, Inc.

Must not be taking: Glucocorticoids, IGF-1R inhibitors

Disqualifiers: Optic neuropathy, Corneal decompensation, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, linsitinib, to determine its effectiveness for thyroid eye disease (TED), which can cause bulging eyes, eye pain, and double vision. The goal is to assess the safety and effectiveness of linsitinib compared to a placebo (a pill with no active medicine) when taken twice daily over 24 weeks. The trial includes different groups: those receiving low doses, high doses, or a placebo. Suitable participants have active, moderate to severe TED due to Graves' Disease or Hashimoto's thyroiditis, affecting daily life and beginning within the last year. Participants must also have their thyroid condition under control without needing immediate eye surgery or other major interventions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have used glucocorticoids (a type of steroid medication) in high doses for thyroid eye disease recently, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that linsitinib, a drug tested for thyroid eye disease (TED), has promising safety results from past studies. One study found the treatment well-tolerated and effective, significantly reducing eye bulging (proptosis) after 24 weeks, with 52% of participants responding positively.

These findings suggest that linsitinib is generally safe, with manageable side effects. Although specific side effects weren't detailed, the trial met its main safety and effectiveness goals, which is encouraging. However, discussing potential risks and benefits with healthcare professionals is always important 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 the IGF-1 receptor, which is different from the current standard treatments like corticosteroids and biologics. Most existing therapies aim to reduce inflammation, but linsitinib works by directly inhibiting pathways involved in the disease's progression. This unique approach offers the potential for improved outcomes, especially for patients who do not respond well to standard treatments. Additionally, the exploration of both low and high doses of linsitinib allows researchers to optimize its effectiveness and safety profile, potentially offering a tailored treatment option for varying severities of the condition.

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

Research shows that linsitinib, an oral medication, holds promise for treating thyroid eye disease (TED). Studies indicate that it reduces symptoms by inhibiting the growth of harmful cells and inducing their death. Tests with mice showed that linsitinib prevented TED from worsening. Reports also suggest it reduces eye area swelling by lowering inflammation. In this trial, participants will receive either a low or high dose of linsitinib, or a placebo. Linsitinib is the first oral treatment to demonstrate both statistical and clinical success in treating TED. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with active, moderate to severe thyroid eye disease (TED) that affects daily life. They should have had TED symptoms within the last year and not need immediate eye surgery or other treatments during the study. Participants must also have controlled thyroid function or mild thyroid issues.

Inclusion Criteria

I have Graves' Disease or Hashimoto's with severe thyroid eye disease.

I don't need eye surgery or treatment now or during the study.

I don't need eye surgery or treatment now or during the study.

Exclusion Criteria

My eye condition has not improved with medication.

I have previously been treated with an IGF-1R inhibitor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linsitinib or placebo orally twice daily for 24 weeks

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
• Placebo

Trial Overview The trial tests Linsitinib, an oral medication taken twice a day, against a placebo to see if it's safe and effective for treating TED over 24 weeks. Linsitinib targets a specific protein involved in TED development.

How Is the Trial Designed?

Group I: Low Dose Active Control 1 Intervention

Active Arm Low Dose Linsitinib

Group II: High Dose Active Control 1 Intervention

Active Arm High Dose Linsitinib

Group III: Placebo Placebo Group 1 Intervention

Placebo Arm

Who Is Running the Clinical Trial?

VasaraGen, Inc.

Lead Sponsor

Trials

1

Recruited

90+

Sling Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06112340

NCT06112340 | Extension Study of Two Doses of Linsitinib ... The overall study objective is to continue to assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of linsitinib in subjects who were enrolled in ...

7. 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).

8. 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 ...