LASN01 for Thyroid Eye Disease

Recruiting at 18 trial locations

Overseen By Lassen Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lassen Therapeutics Inc.

Must be taking: Teprotumumab

Must not be taking: Anti-IGF-1R, Selenium, Biotin

Disqualifiers: Optic neuropathy, Orbital surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing LASN01, a human protein-based medicine, in patients with thyroid eye disease. It aims to help those who haven't had certain treatments before and those who have already tried teprotumumab. The medicine works by blocking part of the immune system to reduce eye problems.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use oral or IV corticosteroids for conditions other than TED in the 6 weeks before starting the trial. You also cannot use selenium within 3 weeks before the trial or biotin within 2 days before any lab tests.

What data supports the effectiveness of the drug LASN01 for Thyroid Eye Disease?

Research on teprotumumab, a drug similar to LASN01, shows it can significantly reduce symptoms of Thyroid Eye Disease by targeting a specific protein involved in the disease. This suggests that LASN01 might also be effective if it works in a similar way. ^{1 2 3 4 5}

What safety data exists for LASN01 (Teprotumumab) in humans?

Teprotumumab, used for treating Thyroid Eye Disease, has been associated with some adverse events, including hearing dysfunction. These side effects vary in frequency and severity, but some may be reversible. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for patients with Thyroid Eye Disease (TED), a condition often associated with Graves' disease, causing eye problems like bulging eyes. Participants should have active symptoms and be suitable for intravenous treatment.

Inclusion Criteria

I have Graves' disease with active thyroid eye disease.

I have moderate-to-severe active thyroid eye disease.

My TED symptoms started less than a year ago.

Exclusion Criteria

I have experienced significant vision loss or changes due to optic nerve issues in the last 6 months.

I haven't taken oral or IV steroids for non-TED conditions in the last 6 weeks.

I have used anti-IGF-1R monoclonal antibody treatment before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of LASN01 or placebo in 3 parallel treatment arms for anti-IGF-1R-naïve TED, and an open-label high dose for post-teprotumumab patients

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LASN01

Trial Overview The study tests LASN01, an antibody targeting the IL-11 receptor, which could help treat TED. Patients will receive one of two different doses of LASN01 or a placebo through IV to compare safety and effectiveness.

Participant Groups

Group I: Randomized low-dose LASN01 (anti-IGF-1R-naïve TED) Experimental Treatment 1 Intervention

Group II: Randomized high-dose LASN01 (anti-IGF-1R-naïve TED) Experimental Treatment 1 Intervention

Group III: Open-label high dose LASN01 (post-teprotumumab, US only) Experimental Treatment 1 Intervention

Group IV: Randomized placebo (anti-IGF-1R-naïve TED) Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Lassen Therapeutics Inc.

Lead Sponsor

Trials

2

Recruited

120+

Findings from Research

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 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 (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 131 patients with thyroid eye disease treated with teprotumumab, 77% experienced significant improvement in proptosis, indicating the drug's efficacy in reducing eye bulging associated with the condition.

While 81.7% of patients reported adverse events, most were mild and reversible; however, serious adverse events occurred in some cases, leading to treatment discontinuation in 12.2% of patients, highlighting the need for careful monitoring and patient education regarding potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. Shah, SA., Amarikwa, L., Sears, CM., et al.[2023]

In a study of 27 patients treated with teprotumumab for thyroid eye disease, 81.5% developed new otologic symptoms, with tinnitus and ear fullness being the most common, but only 45.5% of those with hearing loss experienced symptom resolution after treatment.

Teprotumumab was associated with sensorineural hearing loss in 5 out of 6 patients tested, and a prior history of hearing loss was identified as a significant risk factor, highlighting the need for careful monitoring and screening for hearing issues in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease. Sears, CM., Azad, AD., Amarikwa, L., et al.[2023]

References

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

Efficacy and safety of orbital decompression in treatment of thyroid-associated ophthalmopathy: long-term follow-up of 78 patients. [2013]

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

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

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Surgical rehabilitation of patients with thyroid eye disease: systematic approach]. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Locally produced insulin-like growth factor-1 by orbital fibroblasts as implicative pathogenic factor rather than systemically circulated IGF-1 for patients with thyroid-associated ophthalmopathy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. [2023]

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

Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease-Methodology and Clinical Applications. [2018]

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

Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease. [2023]

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

Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy. [2022]