What is the mechanism of action of this treatment?

Graves' Ophthalmopathy treatments primarily focus on reducing inflammation and modulating the immune response. Teprotumumab, an IGF-1 receptor inhibitor, blocks the insulin-like growth factor-1 receptor involved in the disease's pathogenesis. This inhibition reduces inflammation and tissue expansion, alleviating symptoms like bulging eyes, double vision, and pain. This targeted approach is significant for patients as it addresses the underlying cause of the disease, potentially offering more effective and lasting relief.

What side effects are associated with this type of intervention?

Teprotumumab, an IGF-1 receptor inhibitor, is used in the treatment of Thyroid Eye Disease (TED), a manifestation of Graves' Ophthalmopathy. Common side effects of treatments similar to Teprotumumab include muscle spasms, nausea, alopecia, diarrhea, fatigue, hyperglycemia, and hearing impairment. These side effects are generally manageable, but patients should be closely monitored for any severe reactions.

What prior FDA approvals exist?

Teprotumumab (Tepezza) is an FDA-approved treatment for Thyroid Eye Disease (TED), also known as Graves' Ophthalmopathy. It is an IGF-1 receptor inhibitor that has shown efficacy in reducing symptoms and improving the quality of life for patients with TED. Other treatments for Graves' Ophthalmopathy include glucocorticoids, which reduce inflammation and thyroid hormone secretion, and rituximab, a monoclonal antibody targeting CD20 on B cells, which has been used in severe cases. These treatments aim to manage the autoimmune response and alleviate the symptoms associated with the disease.

What other types of research exist?

As of 2024, promising novel alternatives to Teprotumumab for Graves' Ophthalmopathy include other biologics targeting different pathways involved in the disease. Rituximab, a monoclonal antibody against CD20, has shown potential in reducing inflammation and disease activity. Tocilizumab, an IL-6 receptor inhibitor, is another option that has demonstrated efficacy in reducing symptoms of thyroid eye disease. Additionally, emerging therapies such as small molecule inhibitors targeting specific signaling pathways involved in the disease are under investigation and may offer new treatment options in the near future.

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Monoclonal Antibodies

Teprotumumab for Thyroid Eye Disease

Phase 4

Waitlist Available

Research Sponsored by Amgen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Initial diagnosis of TED within 7 years prior to Screening

Male or female between the ages of 18 and 80 years, inclusive, at Screening

Must not have

Prior orbital irradiation, orbital decompression or strabismus surgery

Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73m2 at Screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 27 to week 136

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial tests the safety and effectiveness of teprotumumab, an IV medication, in adults with Thyroid Eye Disease. It aims to find the best treatment period and assess the need for additional treatment. The medication helps by reducing inflammation and tissue changes in the eyes. Teprotumumab, initially developed for tumor treatment, was later repurposed for thyroid eye disease and approved by the USFDA.

Who is the study for?

Adults aged 18-80 with Thyroid Eye Disease (TED) diagnosed within the last 7 years, not needing immediate eye surgery. Women must test negative for pregnancy and use reliable contraception. Diabetics with HbA1c ≤8% are eligible if they have controlled thyroid levels or mild thyroid dysfunction.

What is being tested?

The trial tests Teprotumumab's safety and effectiveness in treating TED compared to a placebo. It involves three different treatment durations, random assignment of participants to groups, double-masking, and parallel assignment across multiple centers.

What are the potential side effects?

While specific side effects aren't listed here, Teprotumumab is an antibody that could potentially cause immune reactions, infusion-related responses, or exacerbate underlying conditions like inflammatory bowel disease.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I was diagnosed with TED within the last 7 years.

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I am between 18 and 80 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had radiation, surgery to relieve eye pressure, or eye muscle surgery.

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My liver enzymes are high or my kidney function is low.

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I have never been treated with teprotumumab or participated in any teprotumumab trials.

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I do not have any eye conditions that could affect the trial.

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I am scheduled for eyelid surgery during the trial.

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My eye condition has not improved with medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 27 to week 136

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 27 to week 136

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 27 to week 136 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants who experience at least 1 treatment-emergent adverse event (TEAE) and the percentage of participants who experience at least 1 treatment emergent AESI during treatment with teprotumumab

Percentage of Participants who receive re-treatment

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Teprotumumab 8 InfusionsExperimental Treatment1 Intervention

8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) (Cohort 2)

Group II: Teprotumumab 4 InfusionsExperimental Treatment2 Interventions

• 4 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 3 infusions) (Cohort 1) followed by 4 infusions of: * Placebo if a participant is a treatment responder at Week 12 or * Teprotumumab 20 mg/kg if a participant is a treatment non-responder at Week 12

Group III: Teprotumumab 16 InfusionsExperimental Treatment1 Intervention

16 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 15 infusions) (Cohort 3)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

Teprotumumab

2023

Completed Phase 3

~200

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Graves' Ophthalmopathy treatments primarily focus on reducing inflammation and modulating the immune response. Teprotumumab, an IGF-1 receptor inhibitor, blocks the insulin-like growth factor-1 receptor involved in the disease's pathogenesis. This inhibition reduces inflammation and tissue expansion, alleviating symptoms like bulging eyes, double vision, and pain. This targeted approach is significant for patients as it addresses the underlying cause of the disease, potentially offering more effective and lasting relief.