What is the mechanism of action of this treatment?

Graves' Ophthalmopathy treatments often focus on reducing inflammation and abnormal tissue growth around the eyes. Anti-VEGF agents like aflibercept inhibit vascular endothelial growth factor, which decreases inflammation and vascular permeability. This is important for patients as it directly addresses the underlying inflammatory processes and abnormal blood vessel formation, potentially reducing symptoms such as proptosis and vision impairment, and improving overall disease outcomes.

What side effects are associated with this type of intervention?

Common treatments for Graves' Ophthalmopathy include corticosteroids, radiation therapy, and surgical interventions. Anti-VEGF agents like Aflibercept, which reduce inflammation and vascular permeability, are being studied for their potential benefits. Known side effects of anti-VEGF treatments can include injection site reactions, increased intraocular pressure, and rare instances of retinal detachment or thromboembolic events. Corticosteroids, another common treatment, can cause side effects such as weight gain, mood swings, and increased risk of infections. Radiation therapy may lead to dry eyes and, in rare cases, cataracts or retinal damage.

What prior FDA approvals exist?

The FDA has approved teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), for the treatment of Thyroid Eye Disease (TED), also known as Graves' Ophthalmopathy. Teprotumumab works by reducing inflammation and tissue expansion behind the eyes. While aflibercept, an anti-VEGF agent, is being studied for its potential to reduce inflammation and vascular permeability in TED, it is not yet FDA-approved for this specific condition. Other treatments for TED often include corticosteroids and orbital radiotherapy, which also aim to reduce inflammation and manage symptoms.

What other types of research exist?

One promising alternative to Aflibercept for Graves' Ophthalmopathy is the use of monoclonal antibodies targeting angiopoietin-like 3 (ANGPTL3), such as Evinacumab. Evinacumab has shown significant efficacy in reducing LDL-C and triglycerides, which are related to vascular health. Additionally, selective RET inhibitors like Selpercatinib and Pralsetinib, which have shown efficacy in thyroid cancers, may offer potential benefits due to their targeted action on similar pathways involved in inflammation and vascular permeability.

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Anti-VEGF Therapy

Anti-VEGF Therapy for Thyroid Eye Disease (AcTED Trial)

Phase 2

Recruiting

Led By Nahoung Grace Lee, MD

Research Sponsored by Massachusetts Eye and Ear Infirmary

Eligibility Criteria Checklist

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

Must have

Diagnosis of Active Thyroid Eye Disease

Minimum of 18 years-old

Must not have

Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study

Infectious conjunctivitis, keratitis, or endophthalmitis of either eye

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1-90 days

Summary

This trial is testing the safety of injecting a medication called aflibercept, mixed with either a saltwater solution or an enzyme, around the eyes of patients with acute Thyroid Eye Disease. The goal is to see if this treatment can safely reduce swelling and inflammation. Patients will receive multiple injections and be monitored for any side effects. Aflibercept has been used in various retinal diseases, including macular edema and age-related macular degeneration.

Who is the study for?

This trial is for adults over 18 with active Thyroid Eye Disease, showing moderate symptoms. Participants must be able to consent and follow the study plan. Only one eye will be treated, preferably the worse one or non-dominant if equal. Exclusions include prior eye surgeries or treatments, other retinal issues, heart attack or stroke history, aflibercept allergy, infections in the eye area, certain device implants in the eye, recent participation in other drug studies or radiation exposure research.

What is being tested?

The trial tests safety and tolerability of aflibercept injections for acute Thyroid Eye Disease when combined with saline or hyaluronidase (HA), compared to HA alone. Over a period leading up to day 45 from baseline, participants receive three injections while undergoing clinical examinations to monitor adverse events.

What are the potential side effects?

Potential side effects may include discomfort at injection site, inflammation within the eye area due to immune response against VEGF inhibition by aflibercept; allergic reactions are possible especially given known hypersensitivity exclusions.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with active Thyroid Eye Disease.

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I am at least 18 years old.

Exclusion Criteria

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

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I am sexually active and not willing to use birth control during the study.

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I have an eye infection.

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I have a condition affecting my optic nerve that threatens my vision.

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I am not currently using steroids, or if I was, I've stopped for at least 6 weeks.

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I have been treated with drugs targeting blood vessel growth in cancer.

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I've had HA injections for my thyroid eye disease.

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I have previously used Tepezza for treatment.

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I have had a stroke or heart attack before.

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I have eye conditions like diabetic retinopathy that could change VEGF levels in my eye.

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I have had surgery or radiation on my eye area.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1-90 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1-90 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1-90 days for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

: Safety

Secondary study objectives

: Change in Clinical Activity

: Change in Eyelid Retraction/Position

: Change in Ocular Alignment

+9 more

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Saline and afliberceptExperimental Treatment1 Intervention

Group 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept

Group II: Hyaluronidase and afliberceptExperimental Treatment1 Intervention

Group 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept

Group III: Hyaluronidase alonePlacebo Group1 Intervention

Group 3: Sub-tenon injection of HA injection alone

0 / 12Eligibility 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 often focus on reducing inflammation and abnormal tissue growth around the eyes. Anti-VEGF agents like aflibercept inhibit vascular endothelial growth factor, which decreases inflammation and vascular permeability. This is important for patients as it directly addresses the underlying inflammatory processes and abnormal blood vessel formation, potentially reducing symptoms such as proptosis and vision impairment, and improving overall disease outcomes.

Short-term efficacy of intravitreal aflibercept in treatment-naive patients with polypoidal choroidal vasculopathy.Vascular endothelial growth factor acts primarily via platelet-derived growth factor receptor α to promote proliferative vitreoretinopathy.