Aflibercept for Diabetic Macular Edema

Overseen By Andrew Yates, B.A.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Retina Consultants of Orange County

Must be taking: Anti-VEGF therapy

Disqualifiers: Glaucoma, Uveitis, Corneal issues, others

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

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 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a high dose of aflibercept (an injection) for individuals with diabetic macular edema (DME) who have previously undergone vitrectomy surgery. The researchers aim to determine if this treatment can improve vision and extend the intervals between treatments. Participants should have type 1 or type 2 diabetes, experience vision problems due to DME, and have had vitrectomy surgery in the past. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment benefits more patients, offering a chance to contribute to broader knowledge while potentially enhancing personal care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for Aflibercept?

Research has shown that aflibercept, also known as EYLEA, is a safe treatment for diabetic macular edema (DME). It works better than laser treatments, particularly for managing DME. Various studies have demonstrated significant benefits for many patients using aflibercept.

Common side effects include mild issues like eye pain and small bleeds on the eye's surface, known as conjunctival hemorrhage. Serious complications are rare, occurring in less than 0.1% of cases, and can include infections inside the eye, known as endophthalmitis.

Overall, aflibercept is well-tolerated in clinical settings and has FDA approval, indicating a strong safety profile. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using high-dose aflibercept for diabetic macular edema (DME) because it offers a potential new approach for patients who have previously undergone vitrectomy, a procedure that removes the gel from the eye. Unlike standard treatments like ranibizumab or bevacizumab, aflibercept is being evaluated in a treat-extend-stop protocol, which could reduce the frequency of injections by extending the time between treatments once the eye fluid is resolved. This approach not only aims to maintain a fluid-free macula but also improves the convenience for patients by minimizing the number of visits needed for treatment.

What is the effectiveness track record for aflibercept in treating diabetic macular edema?

Research has shown that aflibercept effectively treats diabetic macular edema (DME). Studies have found that aflibercept improves vision and reduces eye swelling. For example, some patients' vision improved from 20/63 to 20/40, allowing them to see more clearly. In this trial, participants with previous vitrectomy and DME will receive a high dose of aflibercept. This approach might allow longer breaks between treatments, especially for those who have had eye surgery. Controlled studies and everyday situations have proven this treatment safe and effective. Overall, aflibercept is a promising option for improving vision in people with DME. ^{1 6 7 8 9}

Who Is on the Research Team?

Sean Adrean, M.D.

Principal Investigator

Retina Consultants of Orange County

Are You a Good Fit for This Trial?

This trial is for patients with diabetic macular edema who have had a vitrectomy surgery. It's designed to see if high doses of Aflibercept can better improve their condition, considering the faster clearance of medication from eyes that have undergone this procedure.

Inclusion Criteria

I am 18 or older with type 1 or type 2 diabetes.

Willing and able to comply with clinic visits and study-related procedures

Provide informed consent signed by study patient or legally acceptable representative

Exclusion Criteria

I have swelling in the retina not caused by diabetes.

Prior intravitreal investigational agents in the study eye (gene therapy, etc.) at any time

IOP ≥28 mmHg in the study eye

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients with DME and previous vitrectomy are treated with high dose aflibercept using a treat-extend-stop protocol until fluid has resolved.

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visual acuity and CMT recorded at each visit.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept

Trial Overview The study tests whether a higher dose (8 mg) of Aflibercept, an anti-VEGF therapy, can provide better outcomes for those with diabetic macular edema after vitrectomy surgery compared to standard treatments.

How Is the Trial Designed?

Group I: Patients with previous vitrectomy and diabetic macular edema treated with high dose aflibercept Experimental Treatment 1 Intervention

Identify patients that have had a previous vitrectomy and have DME that requires anti-VEGF therapy. Then using a treat-extend-stop protocol that I previously published, treat patients with DME using high dose aflibercept, until the fluid has resolved and then extend the time interval in between treatments for those patients, while maintaining a fluid-free macula.

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?

Retina Consultants of Orange County

Lead Sponsor

Trials

1

Recruited

20+

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

Published Research Related to This Trial

A study analyzing over 9 million adverse event reports found that glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with a significantly lower frequency of retinal adverse events compared to other glucose-lowering medications, with a rate of 2.53 per 1000 reports for GLP-1RAs versus 6.62 per 1000 for other medications.

Despite patients on GLP-1RAs having more comorbid conditions and concomitant medications, there was no evidence linking GLP-1RAs to an increased risk of retinopathy progression, suggesting they are a safer option in this regard for treating type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse events in the FDA Adverse Event Reporting System. Fadini, GP., Sarangdhar, M., Avogaro, A.[2022]

A study analyzing 31,542 adverse event reports from the FDA found that semaglutide, a GLP-1 analogue, has a higher potential for misuse and abuse compared to other GLP-1 receptor agonists, with significant reporting odds ratios for issues like drug abuse and withdrawal syndrome.

The findings suggest that semaglutide may be misused as a weight-loss treatment in non-obese individuals, highlighting the need for further research to fully understand its safety profile and the implications of its use outside of approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset. Chiappini, S., Vickers-Smith, R., Harris, D., et al.[2023]

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]

A total of 40,599 adverse events (AEs) were reported for enzalutamide (ENZ) and 13,562 for abiraterone (ABI) in the EudraVigilance database, with over 90% of these AEs classified as serious, indicating significant safety concerns for both treatments.

Older patients (over 65 years) treated with ABI or ENZ are at a higher risk for serious health issues, such as cardiac and infectious disorders, compared to younger patients, highlighting the need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events related to abiraterone and enzalutamide treatment: analysis of the EudraVigilance database and meta-analysis of registrational phase III studies. De Nunzio, C., Lombardo, R., Tema, G., et al.[2021]

Aflibercept, a recombinant fusion protein, effectively inhibits VEGF signaling and has been shown to significantly improve visual acuity in patients with macular edema due to central retinal vein occlusion (CRVO) when administered intravitreally at a dose of 2 mg monthly, as demonstrated in clinical trials with significant improvements over sham injections.

The treatment was generally well tolerated with minimal risk of systemic drug accumulation, making aflibercept a safe and effective option for managing CRVO-related macular edema, although optimal monitoring strategies for long-term efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. Yang, LP., McKeage, K.[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]

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]

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 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 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]

Citations

1. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9486998/

Efficacy and Safety of Aflibercept Therapy for Diabetic Macular ... Aflibercept is effective at improving visual and anatomical outcomes in patients with DME, both in highly controlled settings and in a real-life environment.

3. 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.

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)02577-1/abstract

Intravitreal aflibercept 8 mg in diabetic macular oedema ... A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring ...

5. journals.lww.com journals.lww.com/retinajournal/fulltext/2022/06000/three_year_treatment_outcomes_of_aflibercept.10.aspx

three-year treatment outcomes of aflibercept versus... : retina The rate of serious adverse events was low. Conclusion: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

6. eyleahcp.us eyleahcp.us/s/eylea/diabetic-macular-edema-safety-data

Safety Profile in DME | EYLEA® (aflibercept) Injection The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous ...

7. 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.

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

DME Anatomic Outcomes | EYLEA HD® (aflibercept) Injection Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal ...

9. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02772497

NCT02772497 | 3 Month Outcome of Ziv-aflibercept for DME Multi-studies have shown that Intravitreal aflibercept (Eylea) is effective and safe in diabetic macular edema (DME) treatment and has gained FDA approval but ...