Anti-VEGF Therapy for Thyroid Eye Disease

(AcTED Trial)

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. ^{1 2 3 4 5}

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. ^{1 3 6 7 8}

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. ^{1 3 4 6 7}

Research Team

Nahoung Grace Lee, MD

Principal Investigator

Investigator

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)

Treatment Details

Interventions

• Aflibercept (Anti-VEGF Therapy)
• Hyaluronidase (Enzyme)

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

Massachusetts Eye and Ear Infirmary

Lead Sponsor

Trials

115

Recruited

15,000+

CarolAnn Williams

Massachusetts Eye and Ear Infirmary

Chief Executive Officer

MBA from Harvard Business School

Aalok Agarwala

Massachusetts Eye and Ear Infirmary

Chief Medical Officer since 2019

MD from University of California, Los Angeles

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Aflibercept is a newly approved anti-VEGF drug that effectively suppresses choroidal neovascularization in patients with exudative age-related macular degeneration, showing excellent short-term results in clinical trials.

In pivotal phase 3 trials, aflibercept demonstrated comparable efficacy and safety to ranibizumab while requiring fewer injections, potentially leading to lower overall treatment costs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Browning, DJ., Kaiser, PK., Rosenfeld, PJ., et al.[2013]

In a study of 30 eyes from 23 patients with diabetic macular edema (DME) who previously received an average of 16 injections of ranibizumab and/or bevacizumab, switching to aflibercept resulted in a significant reduction in central subfoveal thickness, improving from 374 µm to 332 µm after the first aflibercept injection (P < .001).

Visual acuity also improved after the switch to aflibercept, with a change from logMAR 0.40 (20/50) to logMAR 0.35 (20/45) (P = .044), suggesting that aflibercept may be a beneficial treatment option for patients with persistent DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for Diabetic Macular Edema in Eyes Previously Treated With Ranibizumab and/or Bevacizumab May Further Improve Macular Thickness. Shah, CP., Heier, JS.[2022]

In a study involving 24 rabbits with chemically induced corneal neovascularization, treatments with aflibercept, betamethasone, or their combination did not significantly reduce neovascularization compared to a control group.

Despite the lack of efficacy in reducing neovascularization, all treatment groups showed lower VEGF levels than the control, suggesting that while these treatments may affect VEGF concentration, they do not effectively reverse the neovascularization process in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Subconjunctival Aflibercept and Betamethasone for the Treatment of Formed Corneal Neovascularization in a Rabbit Model. Eiger-Moscovich, M., Livny, E., Sella, R., et al.[2019]

Aflibercept effectively inhibits vascular endothelial growth factor (VEGF), which is crucial for pathological blood vessel formation, thereby reducing the proliferation of human umbilical vein endothelial cells (HUVEC) in vitro.

The study found that aflibercept maintains its full inhibitory effect for at least 120 hours after being transferred to an injection syringe, which is longer than the manufacturer's specifications suggest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of aflibercept (EYLEA&#174;) on inhibition of human VEGF in vitro. Schicht, M., Hesse, K., Schröder, H., et al.[2017]

Aflibercept (Eylea) treatment showed positive results in improving visual acuity and resolving macular edema in patients with age-related macular degeneration and other retinal diseases.

The treatment was generally safe, with no major side effects or resistance observed, although some patients experienced recurrences of their conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary results of treatment with aflibercept]. Blăjan, C., Nicula, D., Rusu, I.[2015]

Aflibercept (Eylea) is an effective anti-VEGF therapy for neovascular age-related macular degeneration (AMD), showing excellent safety and significant benefits in maintaining vision, as demonstrated in randomized trials.

Aflibercept, administered every 8 weeks after an initial loading dose, is clinically equivalent and statistically noninferior to ranibizumab (Lucentis), which is given every 4 weeks, indicating its potential as a more convenient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for neovascular age-related macular degeneration. Xu, D., Kaiser, PK.[2022]

A study involving 12 patients showed that a single intravitreal injection of ziv-aflibercept for treating choroidal neovascularization due to age-related macular degeneration was safe, with no serious ocular or systemic adverse events reported after 30 days.

While there was only a slight improvement in best-corrected visual acuity after treatment, the absence of significant side effects suggests that ziv-aflibercept could be a viable low-cost alternative for macular disease therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Narayanan, R., Mathai, A., et al.[2022]

References

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

Aflibercept for age-related macular degeneration: a game-changer or quiet addition? [2013]

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]

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]

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

Efficacy of aflibercept (EYLEA&#174;) on inhibition of human VEGF in vitro. [2017]

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

[Preliminary results of treatment with aflibercept]. [2015]

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

Aflibercept: A Review of Its Use in Diabetic Macular Oedema. [2022]

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

Intravitreal aflibercept for neovascular age-related macular degeneration. [2022]

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

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]