Lonigutamab for Thyroid Eye Disease

(TED Trial)

No longer recruiting at 13 trial locations

Overseen By Petrus R. de Jong, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ValenzaBio, Inc.

Must not be taking: Steroids, Teprotumumab, Biologics, others

Disqualifiers: Diabetes, Optic neuropathy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lonigutamab for individuals with Thyroid Eye Disease (TED). Researchers aim to determine if different doses of lonigutamab can reduce symptoms such as bulging eyes. Participants will receive injections of either lonigutamab or a placebo (a substance with no active treatment). Ideal candidates are those who have recently developed TED symptoms and have noticeable eye bulging (3 mm above normal). This study excludes individuals with certain eye conditions or those who have previously used specific treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial requires that you have not used certain medications recently, like steroids for TED, IGF-1R inhibitors, or other immunosuppressive agents. If you're on these, you might need to stop them before joining, but the protocol doesn't specify about other medications.

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

Research shows that lonigutamab is being tested for safety in treating thyroid eye disease. Previous studies found that patients generally tolerate this treatment well. Reported side effects are mostly mild to moderate, such as injection site reactions or mild flu-like symptoms. Serious side effects have not commonly appeared in the research.

Since lonigutamab remains in early clinical trials, some uncertainty about its long-term safety exists. However, the data collected so far appears promising, showing potential without major safety concerns. Always consult a healthcare provider to understand what joining a trial might mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Lonigutamab is unique because it targets the underlying cause of thyroid eye disease, potentially offering more precise treatment than traditional options like corticosteroids or radiation therapy. Unlike these standard treatments, which often address symptoms, lonigutamab is designed to be administered via subcutaneous injections, offering a potentially more convenient and patient-friendly delivery method. Researchers are excited about its ability to work on a molecular level, which could lead to better outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for Thyroid Eye Disease?

Research has shown that lonigutamab, a specially designed antibody, may help treat thyroid eye disease (TED). Early findings suggest it can greatly reduce eye inflammation and other symptoms of TED. In past studies, patients who received lonigutamab experienced significant improvements in their eye condition compared to before treatment. The evidence indicates that this treatment effectively targets and blocks IGF-1R, which plays a key role in TED. In this trial, participants will receive different doses of lonigutamab to evaluate its effectiveness. Overall, early results are promising for lonigutamab's ability to improve symptoms for those with TED. ^{3 6 7 8 9}

Who Is on the Research Team?

Keenan, MD

Principal Investigator

ValenzaBio, Inc.

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-70 with Thyroid Eye Disease (TED), showing eye protrusion and active symptoms within the last 15 months. Participants must have a Clinical Activity Score of at least 4, indicating active disease. They should not have had certain treatments for TED or conditions like inflammatory bowel disease, hearing loss, optic neuropathy, diabetes with high hemoglobin A1c levels, or recent steroid use.

Inclusion Criteria

Your eye sticks out more than 3mm than it should.

The most severely affected eye has a Clinical Activity Score (CAS) of 4 or higher on a 7-item scale.

You have experienced symptoms of TED within the last 15 months before the start of the study.

Exclusion Criteria

You have a condition related to inflammation in the bowel or ongoing issues with your digestive system.

You have a serious ear problem or have had trouble hearing in the past.

You have a condition affecting your optic nerve.

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 lonigutamab via SC injection, with varying schedules depending on cohort

24 weeks

Weekly or every 3-4 weeks, depending on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• VB421

Trial Overview

The study tests Lonigutamab's effectiveness and safety in treating TED compared to a placebo. It's a Phase 1/2 trial where multiple doses are given to participants across various centers. The goal is to see if Lonigutamab can help reduce the severity of TED symptoms.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 1 Intervention

multiple doses of lonigutamab dose 4 administered SC injection every 4 or 3 weeks.

Group II: Cohort 3 Experimental Treatment 2 Interventions

multiple doses of lonigutamab dose 3 administered SC injection every 4 weeks.

Group III: Cohort 2 Experimental Treatment 2 Interventions

multiple doses of dose 2 of lonigutamab administered SC injection weekly

Group IV: Cohort 1 Experimental Treatment 2 Interventions

Single SC injection of dose 1 of lonigutamab or placebo at Day 1 and Day 21

Who Is Running the Clinical Trial?

ValenzaBio, Inc.

Lead Sponsor

Trials

3

Recruited

60+

ACELYRIN Inc.

Lead Sponsor

Trials

9

Recruited

1,100+

Published Research Related to This Trial

In a study of 24 patients with thyroid eye disease, treatment with teprotumumab led to a significant reduction in the cross-sectional areas of extraocular muscles, indicating effective treatment of the condition.

The reduction in muscle size correlated with clinical improvements in symptoms such as diplopia (double vision) and extraocular motility, suggesting that teprotumumab not only reduces muscle size but also enhances functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in Extraocular Muscle Cross-sectional Area and Correlation With Extraocular Motility and Diplopia Following Teprotumumab for Thyroid Eye Disease. Reshef, ER., Marsiglia, M., Bouhadjer, K., et al.[2023]

In a study of 18 patients with thyroid eye disease who did not respond to multiple steroid treatments, Tocilizumab significantly improved disease activity, as shown by a mean reduction of 5.89 points in the Clinical Activity Score (CAS).

Tocilizumab also led to a substantial decrease in thyroid-stimulating immunoglobulin (TSI) levels by 76.18% and improved symptoms such as proptosis and extraocular motility, with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of active corticosteroid-resistant graves' orbitopathy. Pérez-Moreiras, JV., Alvarez-López, A., Gómez, EC.[2022]

Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, has been shown to significantly improve symptoms of thyroid eye disease (TED) in two clinical trials involving 170 patients, with a responder rate of 69% compared to 20% for placebo in the phase 2 study.

The treatment resulted in a substantial reduction in proptosis (eye bulging) and clinical activity scores, with over half of the responders maintaining their improvement for up to 51 weeks after treatment, although it is associated with some common side effects like muscle spasms and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: Interpreting the Clinical Trials in the Context of Thyroid Eye Disease Pathogenesis and Current Therapies. Winn, BJ., Kersten, RC.[2021]

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]

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 is the first and only FDA-approved medical therapy for thyroid-associated ophthalmopathy (TAO), a serious autoimmune condition linked to Graves' disease that can cause significant facial disfigurement and vision loss.

The development of teprotumumab is based on the understanding that the insulin-like growth factor I receptor plays a crucial role in the disease's progression, suggesting potential for similar treatments in other autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy. Smith, TJ.[2021]

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 antibody targeting the IGF-1 receptor, has been shown to effectively reduce proptosis (eye bulging) in patients with non-inflammatory thyroid eye disease (TED), with an average reduction of 2.6 mm after treatment.

The study also found that IGF-1R expression is significantly higher in the orbital tissues of patients with both inflammatory and non-inflammatory TED compared to healthy controls, suggesting that targeting this receptor may be beneficial in treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression. Ugradar, S., Shi, L., Wang, Y., et al.[2022]

Citations

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PMC Search Update

We present data from the first 2 cohorts of an ongoing phase 1/2 dose-ranging study of SC lonigutamab, a high-affinity humanized anti-IGF-1R ...

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Acelyrin unveils phase 3 program design for lonigutamab ...

Acelyrin announced additional data from its phase 2 clinical trial as well as the design for its phase 3 LONGITUDE program of lonigutamab in thyroid eye ...

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MON-360 Lonigutamab (Anti-IGF-1R Monoclonal Antibody ...

Background: Thyroid eye disease (TED) is a chronic debilitating ... Results: Lonigutamab treatment significantly reduced both basal and ...

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A Study to Evaluate the Efficacy and Safety of LASN01 ...

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).

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ACELYRIN, INC. Announces Positive Proof-of-Concept ...

Announces Positive Proof-of-Concept Data From Phase 1/2 Clinical Trial of Lonigutamab as a Subcutaneous Treatment for Thyroid Eye Disease to be ...

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A Study to Evaluate the Efficacy and Safety of LASN01 ...

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).

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12545675/

OR31-06 Lonigutamab (Anti-IGF-1R Monoclonal Antibody ...

OR31-06 Lonigutamab (Anti-IGF-1R Monoclonal Antibody) Induces Efficient Degradation of IGF-1R in Thyroid Eye Disease Orbital Fibroblasts.

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firstwordpharma.com

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ACELYRIN, INC. Announces Additional Phase 2 Data and ...

Totality of data observed with subcutaneous lonigutamab in Thyroid Eye Disease (TED) patients demonstrate potential for efficacy in line ...

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alumis.com

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Preliminary Safety, Efficacy, and Quality of

This study is sponsored by ACELYRIN, INC. Lonigutamab is an investigational therapy not approved by any regulatory authority.