Lonigutamab for Thyroid Eye Disease

(TED Trial)

Recruiting at 12 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

54 Participants Needed

Trial Summary

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.

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

Research on a similar drug, Teprotumumab, which also targets the IGF-1R (insulin-like growth factor 1 receptor), shows it can significantly reduce symptoms of Thyroid Eye Disease, suggesting that Lonigutamab might have similar benefits. ^{1 2 3 4 5}

How does the drug Lonigutamab differ from other treatments for thyroid eye disease?

Lonigutamab is unique because it is an anti-IGF-1R monoclonal antibody, similar to teprotumumab, which targets the insulin-like growth factor 1 receptor involved in the development of thyroid eye disease. This mechanism is different from other treatments like corticosteroids, which are often used but may not be effective for all patients. ^{1 2 6 7 8}

What is the purpose of this trial?

This trial is testing a new medication called lonigutamab to help people with Thyroid Eye Disease (TED). TED causes eye problems due to thyroid issues. Lonigutamab may work by reducing inflammation and other symptoms in the eyes.

Research Team

Keenan, MD

Principal Investigator

ValenzaBio, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

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

Treatment of active corticosteroid-resistant graves' orbitopathy. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression. [2022]

5. United States 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. [2023]

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

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

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

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