Aflibercept for Age-Related Macular Degeneration and Diabetic Macular Edema

(ELARA Trial)

Not currently recruiting at 70 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must be taking: Anti-VEGF

Disqualifiers: Proliferative diabetic retinopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new, higher dose of aflibercept, a medication for eye conditions like age-related macular degeneration (nAMD) and diabetic macular edema (DME). The goal is to determine if this higher dose, administered as frequently as every 4 weeks, is both safe and effective. Researchers monitor for any side effects. Suitable participants include those with nAMD or DME who have received at least three treatments with anti-VEGF medications in the past five months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you have been treated with anti-VEGF medications before joining. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that aflibercept is likely to be safe for humans?

Research has shown that aflibercept is generally well-tolerated by most patients. One study with EYLEA HD® (aflibercept) demonstrated promising results, with patients maintaining good vision with just two doses a year. This indicates the treatment is effective and easy to manage.

Aflibercept has been studied in over 3,000 patients across many trials. These studies have shown it is safe for treating conditions like diabetic macular edema (DME) and age-related macular degeneration (nAMD). While side effects can occur, years of research and experience support the treatment's safety.

For those considering joining a trial, this background suggests that aflibercept is a well-researched and generally safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Aflibercept is unique because it offers a potentially more effective dose for treating age-related macular degeneration and diabetic macular edema. Most treatments for these conditions, like other anti-VEGF medications, aim to reduce abnormal blood vessel growth and fluid leakage in the eye. However, this trial explores a higher 8 mg dose of Aflibercept, which might provide longer-lasting effects and reduce the frequency of eye injections. Researchers are excited about this treatment because it could enhance patient convenience and improve vision outcomes more effectively than current options.

What evidence suggests that aflibercept might be an effective treatment for age-related macular degeneration and diabetic macular edema?

Studies have shown that aflibercept can improve vision in people with age-related macular degeneration (AMD) and diabetic macular edema (DME). It enhances best-corrected visual acuity (BCVA) and reduces central retina thickness, both crucial for eye health. Research indicates that these benefits can persist over time, with some patients requiring only two doses a year to maintain results. Aflibercept has proven as effective as other treatments, such as faricimab, for DME. Overall, aflibercept offers a promising option for enhancing vision and eye health in individuals with AMD and DME. ^{1 3 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with nAMD or DME who have already tried other anti-VEGF treatments. It's not specified who can't join, but typically those with health issues that could interfere with the study or pose extra risks are excluded.

Inclusion Criteria

I've had 3 or more anti-VEGF injections in the last 5 months.

I am over 50 with nAMD needing treatment for CNV lesions.

I am over 18 and have DME affecting the center of my retina.

Exclusion Criteria

My eye swelling is not due to diabetes but another cause.

I have CNV in my eye not caused by nAMD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive aflibercept 8 mg injections every 4 weeks

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept

Trial Overview The study tests aflibercept 8 mg injections in patients with nAMD and DME to assess safety and effectiveness. Participants will receive injections as often as every four weeks to monitor outcomes.

How Is the Trial Designed?

Group I: Aflibercept 8 mg Experimental Treatment 1 Intervention

Participants previously treated with anti-vascular endothelial growth factor (anti-VEGF) medications

Aflibercept is already approved in United States, European Union 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

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead 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

Published Research Related to This Trial

Intravitreal aflibercept significantly improved visual acuity in patients with diabetic macular oedema compared to macular laser photocoagulation and other treatments like bevacizumab and ranibizumab, particularly in those with worse baseline vision, as shown in phase III trials.

Aflibercept was generally well tolerated, making it a promising and effective new treatment option for diabetic macular oedema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a study of 553 patients with diabetic macular edema treated with intravitreal aflibercept over 52 weeks, there was a significant improvement in vision-related quality of life, as measured by the NEI VFQ-25 total score, which increased by an average of +6.11 points.

The treatment also led to notable improvements in best-corrected visual acuity (BCVA) and a reduction in central retinal thickness (CRT), while the safety profile was consistent with known effects, with 53.6% of patients experiencing treatment-emergent adverse events, including a low incidence of serious ocular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study. Garweg, JG., Stefanickova, J., Hoyng, C., et al.[2020]

In a study of 26 patients with refractory diabetic macular edema (DME), ziv-aflibercept treatment led to significant improvements in visual acuity and macular thickness after switching from previous anti-VEGF therapies.

No adverse ocular or systemic side effects were reported, indicating that ziv-aflibercept is a safe option for patients who did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. Ashraf, M., Kayal, HE., Souka, AAR.[2022]

In a study of 40 patients with neovascular age-related macular degeneration who switched from ranibizumab to aflibercept, contrast sensitivity improved significantly from baseline to week 12, indicating enhanced visual function.

The central retinal thickness decreased significantly, suggesting that aflibercept may effectively reduce fluid accumulation in the retina, which is crucial for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of contrast sensitivity and other visual function outcomes in neovascular age-related macular degeneration patients after treatment switch to aflibercept from ranibizumab. Nixon, DR., Flinn, NA.[2022]

In a study of 90 eyes from 67 patients switched from ranibizumab to aflibercept for diabetic macular edema, there was a significant improvement in visual acuity, with an average increase of 4 Early Treatment Diabetic Retinopathy Study letters after 12 months (p=0.0053).

Anatomical outcomes also showed positive trends, with a reduction in central foveal thickness by 136.8 μm, although this change was not statistically significant (p=0.69), indicating that aflibercept may be effective in improving vision in patients previously treated with ranibizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab. Lukic, M., Williams, G., Shalchi, Z., et al.[2021]

In a study of 92 diabetic patients treated with intravitreal aflibercept for diabetic macular edema, significant improvements were observed after 12 months, with average visual acuity increasing from 59.7 to 69.6 Early Treatment Diabetic Retinopathy Study letters.

Aflibercept treatment also led to a notable reduction in central foveal thickness from 431 µm to 306 µm, indicating effective anatomical changes alongside improved vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes. Lukic, M., Williams, G., Shalchi, Z., et al.[2022]

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]

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]

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 40 patients with diabetic macular edema (DME), a treat-and-extend regimen using aflibercept showed significant improvement in central subfield macular thickness (CST) but limited gains in best-corrected visual acuity (BCVA) after one year.

The study found that patients who responded well to initial treatments (gaining 4 or more letters in vision) experienced greater overall vision improvement, suggesting that early response to treatment may predict better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial. Hirano, T., Toriyama, Y., Takamura, Y., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5667400/

Effects of Aflibercept for Neovascular Age-Related Macular ... The results showed that aflibercept helped improve BCVA and decrease CRT in routine clinical practice. Treatment indications, follow-up time, and regimens ...

2. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/three-year-results-eylea-hdr-aflibercept-injection-8-mg-patients

Three-Year Results for EYLEA HD® (aflibercept) Injection ... The latest three-year EYLEA HD results show a substantial portion of patients were able to sustain visual and anatomic benefits with only two doses a year.

3. eyleahcp.us eyleahcp.us/s/eylea/diabetic-macular-edema-vision-outcomes

DME: Vision Outcomes - eylea EYLEA Achieved Rapid and Sustained Outcomes in DME · EYLEA® (aflibercept) Injection mean change in BCVA year 1, Chart ; EYLEA Improved Vision from 20/63 to 20/40.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950253525000358

Short-term outcomes of faricimab and aflibercept 8 mg in ... Faricimab and aflibercept 8 mg show comparable efficacy in treating DME. Both treatments significantly improve BCVA and reduce central retinal thickness.

5. ophthalmologytimes.com ophthalmologytimes.com/view/regeneron-to-highlight-real-world-efficacy-of-aflibercept-8-mg-eylea-hd-in-wamd-dme-and-dr

Regeneron to highlight real-world efficacy of aflibercept 8 ... Regeneron has announced the upcoming presentation of 27 abstracts, including 8 oral presentations on aflibercept injection 8 mg (Eylea HD) in wet age-related ...

6. eyleahdhcp.com eyleahdhcp.com/dme/clinical-trial-data/anatomic-outcomes

DME Anatomic Outcomes | EYLEA HD® (aflibercept) Injection Find information on the anatomic outcomes for EYLEA HD® (aflibercept) Injection for patients with Diabetic Macular Edema (DME). See Important Safety Info and

7. eyleahcp.us eyleahcp.us/s/eylea/about-eylea

About EYLEA® Treatment | EYLEA® (aflibercept) Injection EYLEA efficacy and safety is backed by 10 pivotal studies evaluating clinical outcomes in over 3000 patients.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06491914

A Phase 3b, Single-Arm Study of Aflibercept 8 mg Dosed ... The aim of the study is to see how safe and effective aflibercept HD injections are when given as frequently as every 4 weeks.