High Dose Aflibercept for Macular Degeneration

(HEIRLOOM Trial)

Overseen By Cynthia lacasse

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Clinique de Retine de l'est

Must be taking: Aflibercept

Must not be taking: Anti-VEGF

Disqualifiers: Other maculopathy, Pregnancy, 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

Compensation: Varies

Number of Visits: 9

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best treatment schedule for patients with wet age-related macular degeneration (wAMD) who are switching to a high-dose version of EYLEA® (aflibercept, an injection). Participants currently using EYLEA® 2mg will either receive high-dose injections monthly for the first three months or maintain their current schedule. The goal is to determine if the new method is as effective and potentially reduces the number of injections needed. Ideal candidates have been treating their wAMD with EYLEA® 2mg and have completed at least five prior injections. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you have been treated with EYLEA® (aflibercept 2mg) before participating. If you are using a different treatment in the other eye, you may not be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that high-dose aflibercept (8 mg) is generally safe for people with wet age-related macular degeneration (wAMD). In studies, only 1.7% of participants experienced serious side effects, indicating that most did not encounter severe problems after treatment.

Patients who received aflibercept 8 mg every 12 or 16 weeks showed improved vision and eye health, with no new safety issues over 44 weeks, indicating the treatment is well-tolerated.

Furthermore, long-term results revealed that many patients maintained benefits with just two doses a year, further supporting its safety and effectiveness.

Overall, the evidence is promising, suggesting the treatment is likely safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for macular degeneration?

Researchers are excited about high-dose aflibercept (EYLEA® HD) for macular degeneration because it offers a potentially more effective dosing strategy. Unlike the standard treatment with EYLEA® at 2mg, this new approach uses an 8mg dose, which could mean fewer injections and less burden for patients while maintaining or improving treatment effectiveness. By adjusting the treatment intervals based on each patient's response, it offers a more personalized and potentially less intrusive management of the condition.

What is the effectiveness track record for EYLEA® HD in treating wet age-related macular degeneration?

Studies have shown that EYLEA® HD (aflibercept 8mg) effectively treats wet age-related macular degeneration (wAMD). In this trial, participants will join different treatment arms to evaluate EYLEA® HD. Research indicates that patients using EYLEA® HD often maintain vision improvements with fewer injections, sometimes requiring only two doses a year. Trials demonstrated that EYLEA® HD provided similar vision improvements compared to the standard 2mg dose, with an increase of about +6.7 in Best Corrected Visual Acuity (BCVA, a measure of visual clarity). It also significantly reduced retinal thickness, which is crucial in managing wAMD. Overall, EYLEA® HD has proven to be a strong option for managing wAMD. ^{3 6 7 8 9}

Who Is on the Research Team?

Andrei Szigiato, Docteur

Principal Investigator

Clinique de Retine de l'est

Are You a Good Fit for This Trial?

This trial is for adults over 18 with wet age-related macular degeneration (wAMD) who are already being treated with EYLEA® (aflibercept 2mg). It's not suitable for those who haven't had treatment injections for wAMD before or have conditions that might exclude them from the study.

Inclusion Criteria

I am over 18 years old.

One or both of my eyes qualify for the study.

I have received 3 initial and 2 maintenance injections of aflibercept 2mg.

Exclusion Criteria

I do not have any other eye conditions like macular dystrophy or scars from previous treatments.

Is currently enrolled in another clinical study or observational study

If the patient is pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EYLEA® HD (aflibercept 8mg) injections every month for the first 3 months, followed by an extension of the treatment interval based on clinical response

3 months

3 visits (in-person) for initial injections, followed by extended intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 6 and 12 months

12 months

Interim analysis at 6 months, final analysis at 12 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term based on clinical response

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept

Trial Overview The HEIRLOOM study is testing if it's better to maintain current treatment intervals or load up on a higher dose of EYLEA® HD (aflibercept 8mg) in patients with wAMD. The goal is to find out the most effective regimen when switching from regular EYLEA® doses.

How Is the Trial Designed?

Group I: Maintenance interval group Experimental Treatment 1 Intervention

patients who are currently being treated with EYLEA® (aflibercept 2mg) will be switched to EYLEA® HD (aflibercept 8mg) and maintain the current treatment interval that they had with EYLEA® (aflibercept 2mg), followed by an extension of therapy (or increase in treatment dosing interval) based on clinical response. This is the "off-label" treatment regimen that we are testing to see if it is as effective and involves less treatment burden.

Group II: Loading interval group Active Control 1 Intervention

patients who are currently being treated with EYLEA® (aflibercept 2mg) will be switched to EYLEA® HD (aflibercept 8mg) and receive injections every month for the first 3 months followed by an extension (or increase in dosing interval) of therapy based on clinical response. This is the "on label" treatment regimen approved by Health Canada.

Who Is Running the Clinical Trial?

Clinique de Retine de l'est

Lead Sponsor

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Citations

1. eyleahcp.us eyleahcp.us/s/eylea/wet-amd-anatomy-outcomes

Wet AMD Clinical Trial Results | EYLEA® (aflibercept) Injection EYLEA decreased mean central retinal thickness by ≈130 μm to 150 μm depending upon dosing schedule across VIEW 1 and VIEW 2.

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. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605527/

Aflibercept 8 mg/0.07 mL (Eylea HD) - NCBI Bookshelf - NIH Moderate certainty evidence showed that aflibercept 8 mg every 12 weeks or 8 mg every 16 weeks likely results in little to no difference in important outcomes ...

4. bmjophth.bmj.com bmjophth.bmj.com/content/10/1/e002091

Real-world efficacy and safety of 8 mg aflibercept in ... Patients in the aflibercept 8 mg arms demonstrated non-inferiority in BCVA improvements compared with the aflibercept 2 mg arm, gaining +6.7 ...

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 reveals positive results from multiple trials evaluating Eylea HD (aflibercept) injection 8 mg. February 10, 2025. Accessed April ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39991354/

Efficacy and Safety of High-Dose Intravitreal Aflibercept in ... There was a complication rate of 1.7% for serious adverse effects. In conclusion, higher doses of aflibercept (>2 mg) are safe and effective for ...

7. nature.com nature.com/articles/s41433-024-03543-x

Efficacy and safety of high-dose Intravitreal aflibercept 8 ... Patients with neovascular age-related macular degeneration who received aflibercept 8 mg every 12 or 16 weeks achieved similar visual and anatomic improvements.

8. aaojournal.org aaojournal.org/article/S0161-6420(25)00532-9/fulltext

Intravitreal Aflibercept 8 mg in Neovascular Age-Related ... Conclusions. Aflibercept 8 mg delivered sustained disease control in patients with nAMD, maintaining improvements in visual and anatomic ...

9. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/2807967

Effect of High-Dose Intravitreal Aflibercept, 8 mg, in ... No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of ...