Lonigutamab for Thyroid Eye Disease

(TED Trial)

Recruiting in Palo Alto (17 mi)

+12 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: ValenzaBio, Inc.

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

Disqualifiers: Diabetes, Optic neuropathy, others

No Placebo Group

Trial Summary

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.

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.

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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.

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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

You are between 18 and 70 years old.

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.

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Clinical Research Site Beverly Hills, CA

Clinical Research Site New York City, NY

Clinical Research Site Atlanta, GA

Clinical Research Site Jacksonville, FL

More Trial Locations

Who Is Running the Clinical Trial?

ValenzaBio, Inc. Lead Sponsor

ACELYRIN Inc. Lead Sponsor

References

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

Treatment of active corticosteroid-resistant graves' orbitopathy. [2022] To assess the efficacy of Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, in thyroid eye disease patients refractory to multiple intravenous steroids.

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

Teprotumumab for the treatment of chronic thyroid eye disease. [2022] Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED.

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

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. [2023] To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab.

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

Teprotumumab for non-inflammatory thyroid eye disease (TED): evidence for increased IGF-1R expression. [2022] Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED). Herein, we investigate the impact of teprotumumab on patients with non-inflammatory TED. We also investigate the expression of the IGF-1R on orbital tissues from patients with inflammatory and non-inflammatory TED compared to controls.

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] To quantify changes in extraocular muscle (EOM) cross-sectional areas (CSA) on orbital imaging in patients with thyroid eye disease before and after teprotumumab treatment, and assess for correlation with clinical outcomes.

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] Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P

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

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. [2023] Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment of thyroid eye disease (TED). The clinical trials leading to its approval enrolled patients with recent disease onset and significant inflammatory symptoms and signs. Subsequent real-world teprotumumab use in patients with longer duration of disease also may be effective, and there have been several publications reporting on experience in these patient groups.

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

Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy. [2021] Thyroid-associated ophthalmopathy (TAO) has remained a vexing and poorly managed autoimmune component of Graves' disease where the tissues surrounding the eye and in the upper face become inflamed and undergo remodeling. This leads to substantial facial disfigurement while in its most severe forms, TAO can threaten eye sight. In this brief paper, I review some of the background investigation that has led to development of teprotumumab as the first and only US FDA approved medical therapy for TAO. This novel treatment was predicated on recognition that the insulin-like growth factor I receptor plays an important role in the pathogenesis of TAO. It is possible that a similar involvement of that receptor in other autoimmune disease may lead to additional indications for this and alternative insulin-like growth factor I receptor-inhibiting strategies.