Aflibercept Injections for Diabetic Macular Edema

Overseen By Wenli Xie, MSc.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Must not be taking: Systemic steroids

Disqualifiers: Ocular inflammatory, Autoimmune, Glaucoma, others

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

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: 4

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Aflibercept injections for Diabetic Macular Edema (DME), a serious eye condition caused by diabetes. The researchers aim to determine if certain inflammation markers can predict treatment response. Participants will receive monthly eye injections for four months. Suitable candidates have diabetes-related vision problems diagnosed by a retina specialist and have not received similar eye treatments before.

As an unphased trial, this study provides a unique opportunity to contribute to understanding and improving DME treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are actively taking systemic steroids.

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

Research has shown that aflibercept is a safe treatment for diabetic macular edema (DME). It is effective and approved by the FDA for treating DME. Studies have found that serious side effects are rare, occurring in less than 0.1% of injections.

Common side effects include minor issues such as eye pain or bleeding in the eye, affecting about 5% or more of patients. Overall, aflibercept is considered well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for diabetic macular edema, such as laser therapy or corticosteroids, aflibercept is unique because it specifically targets and traps Vascular Endothelial Growth Factor (VEGF), which plays a key role in the formation of abnormal blood vessels in the eye. By directly inhibiting VEGF, aflibercept helps reduce fluid leakage and swelling in the retina more effectively. Researchers are excited about aflibercept because it offers a targeted approach that can potentially provide better visual outcomes with fewer side effects compared to traditional methods. Additionally, its monthly intravitreal injection schedule can be more convenient for patients, offering a structured and predictable treatment plan.

What evidence suggests that Aflibercept might be an effective treatment for Diabetic Macular Edema?

Research has shown that aflibercept, which participants in this trial will receive, effectively treats diabetic macular edema (DME). Studies have found that patients receiving aflibercept injections often experience improved vision, with many improving from 20/63 to 20/40 vision. This improvement means their vision becomes clearer and sharper over time. Additionally, aflibercept reduces retinal thickness, which is crucial for managing DME. Multiple studies and real-world evidence support these findings, highlighting aflibercept as a safe and effective treatment for those with DME. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with Diabetic Macular Edema (DME) by a retina specialist, who have not received prior treatments like anti-VEGF injections or laser treatment for DME in the last three months. Participants should have a visual acuity score between 25 and 75 letters and must be willing to sign a consent form.

Inclusion Criteria

Diagnosis of DME by a retina specialist

Age: 18 or older

VA between 25 and 75 letters at baseline

Exclusion Criteria

Previous anti-VEGF intravitreal treatment in affected eye

Previous laser treatment for DME within last 3 months

Any ocular surgery within the last 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 2mg/ml dose of VEGF-Trap (Aflibercept) injected intravitreally at the start of every month for 4 months

4 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept

Trial Overview The study tests Aflibercept injections [Eylea] on patients with DME to see if levels of inflammatory markers before treatment can predict how well they'll respond. The goal is to understand better the role inflammation plays in DME.

How Is the Trial Designed?

Group I: Aflibercept Injection [Eylea] group Experimental Treatment 1 Intervention

Intervention: Subjects will be receiving a (2mg/ml) dose of VEGF-Trap, injected intravitreally at the start of every month, for the 4 months duration of the trial.

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?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

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]

Intravitreal injections of ziv-aflibercept (IVI-ZA) over 48 weeks were found to be safe, with no significant changes in electroretinogram results or any systemic or ocular complications in the seven patients with diabetic macular edema (DME).

The treatment led to a significant improvement in best-corrected visual acuity (BCVA) after the first injection, which was maintained throughout the study, and a notable decrease in central retinal thickness (CRT), indicating its efficacy in managing DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes. de Andrade, GC., de Oliveira Dias, JR., Maia, A., et al.[2019]

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]

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 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 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 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]

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/PMC12496451/

Real-World Functional and Anatomic Outcomes With ... Purpose: To assess clinical outcomes in diabetic macular edema (DME) patients treated with high-dose aflibercept 8.0 mg (HDA), focusing on ...

2. 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.

3. 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 ...

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. retinatoday.com retinatoday.com/articles/2019-mar/real-world-outcomes-of-anti-vegf-therapy-for-diabetic-macular-edema-in-the-united-states

Real-World Outcomes of Anti-VEGF Therapy for Diabetic ... Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial.

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

Efficacy and Safety of Aflibercept Therapy for Diabetic Macular ... Aflibercept is a safe and effective therapy option for DME in the clinical setting, performing superiorly to laser photocoagulation.

7. 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 ...

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 ...