LASN01 for Thyroid Eye Disease

No longer recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LASN01 to determine its safety and effectiveness for people with thyroid eye disease (TED), a condition causing bulging eyes and discomfort. LASN01 is an antibody targeting a specific protein involved in inflammation. The trial includes different groups: one for those without specific prior treatment and another for those who have previously received teprotumumab. Individuals with moderate-to-severe TED related to Graves' disease, who haven't undergone certain treatments or surgeries, might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that LASN01 appears safe. In earlier studies, most patients experienced only mild side effects, which were not serious and generally easy to manage. These results suggest that LASN01 could be a safe option for people with thyroid eye disease, although further studies are underway to confirm this. ^{1 2 3 4 5}

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

Unlike the standard treatments for Thyroid Eye Disease, which often include corticosteroids and teprotumumab, LASN01 is unique because it targets the IGF-1 receptor in a new way. This treatment is exciting because it offers two different dosing strategies: a randomized low-dose for those who haven't received IGF-1R therapies before, and a high-dose option specifically for patients in the US who have previously been treated with teprotumumab. This new mechanism of action and the tailored dosing options could potentially provide more effective and personalized treatment for patients with Thyroid Eye Disease.

What evidence suggests that LASN01 could be an effective treatment for thyroid eye disease?

Research shows that LASN01 targets a specific part of the body involved in thyroid eye disease (TED). Early lab studies indicated that LASN01 slowed cell growth and reduced a substance causing swelling in TED. These studies used cells from TED patients, suggesting that LASN01 might help manage the condition. In this trial, participants will receive either a low dose or high dose of LASN01, or a placebo, to further evaluate its effectiveness. Although information from human studies is still being gathered, these early findings offer hope that LASN01 could effectively treat TED symptoms. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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/NCT06226545

NCT06226545 | A Study to Evaluate the Efficacy and ... LASN01 is a novel, fully human antibody directed against the human IL-11 receptor being developed for treatment of patients with thyroid eye disease (TED).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12347536/

Redefining Treatment Paradigms in Thyroid Eye Disease Lassen Therapeutics, Inc A Study to Evaluate the Efficacy and Safety of LASN01 in Patients with Thyroid Eye Disease. [(accessed on 13 June ...

3. ophthalmologytimes.com ophthalmologytimes.com/view/lassen-therapeutics-presents-new-data-on-lasn01-for-the-treatment-of-thyroid-eye-disease-ted-

Lassen Therapeutics presents new data on LASN01 for the ... “In preclinical studies, LASN01 led to the suppression of cell proliferation and hyaluronan secretion from primary TED orbital fibroblasts, in ...

4. med.stanford.edu med.stanford.edu/content/dam/sm/ophthalmology/documents/TED%202024%20RCT%20LETTER%20V1.pdf

STANFORD UNIVERSITY SCHOOL OF MEDICINE Masked, Placebo-Controlled Study to Determine the Efficacy and Safety of LASN01 in Patients with Thyroid Eye Disease. 5FN=<-;O= The ...

5. lassentherapeutics.com lassentherapeutics.com/news/lassen-therapeutics-announces-closing-of-oversubscribed-85-million-series-b-financing-and-announces-first-patient-dosed-in-the-phase-1-trial-evaluating-lasn01-in-thyroid-eye-disease/

Lassen Therapeutics Announces Closing of Oversubscribed ... Lassen recently presented data using orbital fibroblast cells from TED patients demonstrating that LASN01 suppresses multiple markers associated ...

6. academic.oup.com academic.oup.com/jes/article/8/Supplement_1/bvae163.2036/7812997

6417 Phase 1 Healthy Volunteer Data Supports Phase 2 ... LASN01 is the only agent being developed for TED which offers the possibility of addressing the fibro-inflammatory pathology of TED.

7. trialx.com trialx.com/clinical-trials/listings/235978/a-study-to-evaluate-the-safety-preliminary-efficacy-and-pharmacokinetic-properties-of-lasn01-in-healthy-subjects-and-in-patients-with-pulmonary-fibrosis-or-thyroid-eye-disease/

Thyroid Eye Disease ) ( NCT05331300 ) The primary objective of this study is to evaluate the safety and tolerability of LASN01, and the secondary objective is to evaluate the ...