Anti-VEGF Therapy for Thyroid Eye Disease

(AcTED Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Nahoung Grace Lee, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Massachusetts Eye and Ear Infirmary

Must not be taking: Steroids, Teprotumumab, Anti-VEGF

Disqualifiers: Stroke, Myocardial infarction, others

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are currently taking systemic or topical steroids, you will need to stop and have a 6-week period without them before joining the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

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

Aflibercept has been shown to be effective in treating conditions like age-related macular degeneration and diabetic macular edema by reducing abnormal blood vessel growth and swelling in the eye, which suggests it might help with similar issues in Thyroid Eye Disease.

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Is anti-VEGF therapy, like Aflibercept, generally safe for humans?

Aflibercept, used in treatments for eye conditions like diabetic macular edema and age-related macular degeneration, has shown an excellent safety profile in clinical trials, meaning it is generally safe for humans.

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

Aflibercept is unique because it is a potent anti-VEGF drug that works by blocking the action of VEGF, a protein that promotes the growth of abnormal blood vessels. This mechanism is different from other treatments for thyroid eye disease, which may not specifically target VEGF. Additionally, Aflibercept is administered as an injection, which can offer a different dosing schedule compared to other therapies.

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Eligibility Criteria

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.

Inclusion Criteria

Only one eye will be enrolled. The worse eye (demonstrating worse HVF results, worse restricted motility, worse visual acuity, worse edema, worse proptosis, worse eyelid retraction) will be enrolled. If both eyes are equivalent, we will enroll the non-dominant eye.

I have been diagnosed with active Thyroid Eye Disease.

I am at least 18 years old.

Exclusion Criteria

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

Pregnant or breast-feeding women

I have an eye infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three injections of aflibercept with saline, aflibercept with hyaluronidase, or hyaluronidase alone

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

2 visits (in-person)

Participant Groups

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.

Group I: Saline and aflibercept Experimental Treatment 1 Intervention

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

Group II: Hyaluronidase and aflibercept Experimental Treatment 1 Intervention

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

Group III: Hyaluronidase alone Placebo Group 1 Intervention

Group 3: Sub-tenon injection of HA injection alone

Aflibercept is already approved in United States, European Union, United States for the following indications:

🇺🇸 Approved in United States as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

🇪🇺 Approved in European Union as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

🇺🇸 Approved in United States as Zaltrap for:

• Metastatic Colorectal Cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mass Eye and Ear Boston, MA

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary Lead Sponsor

Regeneron Pharmaceuticals Industry Sponsor

References

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

Aflibercept for age-related macular degeneration: a game-changer or quiet addition? [2013] To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti-vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer).

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

Aflibercept for Diabetic Macular Edema in Eyes Previously Treated With Ranibizumab and/or Bevacizumab May Further Improve Macular Thickness. [2022] To evaluate the short-term anatomic and visual outcomes after aflibercept (Eylea; Regeneron, Tarrytown, NY) in eyes with diabetic macular edema (DME) previously treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA) and/or bevacizumab (Avastin; Genentech, South San Francisco, CA).

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Subconjunctival Aflibercept and Betamethasone for the Treatment of Formed Corneal Neovascularization in a Rabbit Model. [2019] To compare the efficacy of aflibercept (Eylea®), a potent antivascular endothelial growth factor (VEGF) agent, with betamethasone (Celestone®) and placebo for the treatment of formed corneal neovascularization in a rabbit model.

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of aflibercept (EYLEA®) on inhibition of human VEGF in vitro. [2017] Label="INTRODUCTION" NlmCategory="BACKGROUND">Pathological formation of blood vessels plays a key role in the growth and metastasis of tumors and also in several serious ophthalmological diseases such as wet age-related macular degeneration (AMD) or diabetic retinopathy. In AMD treatment, aflibercept (tradename EYLEA®) is used to deactivate the underlying pathological neovascularisation. Aflibercept is a recombinant fusion protein which binds to vascular endothelial growth factor (VEGF) receptors, thereby inhibiting VEGF pathway activation. VEGF is one of the most important angiogenesis factors.

5. Romania pubmed.ncbi.nlm.nih.gov

[Preliminary results of treatment with aflibercept]. [2015] The paper presents the first results concerning the Aflibercept (Eylea) treatment, the last antiVEGF approved for treatment of the age related macular degeneration (AMD), neovascular form and for macular edema due to the central retinal vein occlusion. The treatment was applied to patients presenting AMD, ME and other diseases: myopic and idiopatic choroidal neovascularisation, central serous choroidopathy (CSC) or diabetic macular edema (DME). The results were good: improvement of the visual acuity, resolution of the intraretinal fluids and macular edema. Although we did not notice major side-effects, resistance or tachyphylaxis, we noticed some recurrences.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Aflibercept: A Review of Its Use in Diabetic Macular Oedema. [2022] Aflibercept (Eylea(®)) is an anti-vascular endothelial growth factor agent indicated for intravitreal use in the treatment of diabetic macular oedema. In patients with diabetic macular oedema, significantly greater improvements from baseline to week 52 in visual acuity were seen with intravitreal aflibercept versus macular laser photocoagulation in the phase III VISTA-DME and VIVID-DME trials, and versus intravitreal bevacizumab or ranibizumab in those with worse visual acuity at baseline (i.e. Early Treatment Diabetic Retinopathy Study letter score of

7. England pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for neovascular age-related macular degeneration. [2022] Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in patients over the age of 50 in the western world. Intravitreally administered anti-VEGF drugs have been developed to halt neovascular growth in AMD. Randomized trials have demonstrated the excellent safety profile and significant benefit of anti-VEGF therapy in maintaining vision. Aflibercept (Eylea(®); Regeneron, NY, USA) is a soluble decoy receptor against VEGF that offers greater potency and binding affinity than other anti-VEGF drugs. Having received US FDA approval for neovascular AMD in November 2011, aflibercept given every 8 weeks after a loading dose was 'clinically equivalent' and statistically noninferior to the current FDA-approved therapy ranibizumab (Lucentis(®); Genentech, CA, USA), given every 4 weeks. This article discusses the clinical background of AMD, development of aflibercept, results of the clinical trials and the future role of aflibercept in ocular neovascular diseases.

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

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022] To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration.