Linsitinib for Thyroid Eye Disease

(LIDS Trial)

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

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the safety and effectiveness of linsitinib, an oral medication taken regularly, in patients with moderate to severe thyroid eye disease. Linsitinib works by blocking a protein that contributes to the disease, aiming to reduce symptoms and improve eye health.

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.

What data supports the effectiveness of the drug Linsitinib for treating Thyroid Eye Disease?

Research shows that Linsitinib, which targets specific receptors involved in Thyroid Eye Disease, can reduce disease development and progression. Similar drugs like teprotumumab, which also target the same receptors, have been effective in treating this condition. ^{1 2 3 4 5}

How is the drug Linsitinib different from other treatments for thyroid eye disease?

Linsitinib is unique because it is a dual inhibitor targeting both the insulin-like growth factor 1 receptor (IGF-1R) and the insulin receptor (IR), which may help reduce disease progression in thyroid eye disease. This is different from teprotumumab, which only targets IGF-1R. ^{4 5 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A New Era in the Treatment of Thyroid Eye Disease. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for chronic thyroid eye disease. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Effect of teprotumumab on intraocular pressure in thyroid-associated ophthalmopathy. [2022]