Aflibercept for Age-Related Macular Degeneration

Enrolling by invitation at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Exegenesis Bio

Disqualifiers: Not enrolled in parent study

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to ensure the long-term safety of a treatment called EXG102-031 (also known as Aflibercept) for individuals with neovascular (wet) age-related macular degeneration (nAMD). In nAMD, abnormal blood vessels grow and leak in the eye, causing blurry vision. EXG102-031 is designed to prevent this vessel growth and leakage. Participants who completed a previous study with EXG102-031 and wish to join this follow-up must have been part of the original study and be willing to adhere to the trial's procedures. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 is best to discuss this with the study team or your doctor.

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

Research has shown that aflibercept is safe for treating neovascular age-related macular degeneration (nAMD). The FDA has approved it for this use. Studies have found that most patients tolerate aflibercept well. The most common side effects are mild, such as eye pain or redness, while serious side effects are rare. This indicates that aflibercept has a strong safety record for people with nAMD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Aflibercept is unique because it targets vascular endothelial growth factor (VEGF), which plays a key role in the abnormal blood vessel growth and leakage that lead to vision loss in age-related macular degeneration (AMD). Unlike other treatments that may require more frequent dosing, aflibercept is designed for longer intervals between injections, potentially offering more convenience for patients. Researchers are excited about aflibercept because it not only inhibits VEGF but also another growth factor involved in the disease process, potentially offering a more comprehensive approach to managing AMD.

What is the effectiveness track record for Aflibercept in treating age-related macular degeneration?

Research has shown that aflibercept effectively treats wet age-related macular degeneration (nAMD), a condition where abnormal blood vessels impair vision. Studies such as VIEW 1 and VIEW 2 demonstrated that aflibercept helps manage this condition by reducing fluid build-up and improving vision clarity. It blocks a protein called VEGF, which causes these abnormal vessels to grow. Some research suggests that higher doses of aflibercept may offer additional benefits. Overall, evidence supports aflibercept's ability to improve vision in people with nAMD. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with wet age-related macular degeneration (nAMD) who have previously been treated with EXG102-031 under the main study. It's a long-term follow-up to monitor safety.

Inclusion Criteria

Must be willing and able to comply with all study procedures.

Are willing and able to sign the study written informed consent form

I was part of the EXG102-031-211 study and received EXG102-031 treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Study Treatment

Participants received EXG102-031 gene therapy and were monitored for safety and tolerability over 52 weeks

52 weeks

Long-term Follow-up

Participants are monitored for safety and tolerability of EXG102-031 for an additional 36 months, with regular ocular assessments and potential supplemental therapy with aflibercept

36 months

Regular clinic visits

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept

Trial Overview

The intervention being studied is Aflibercept (2.0 mg), which aims to block abnormal blood vessel growth in the eye, potentially reducing vision leakage and damage in nAMD patients.

How Is the Trial Designed?

Group I: All participants who completed the main study of EXG102-031 Experimental Treatment 1 Intervention

All subjects who enroll in this LTFU study have received the experimental treatment with EXG102-031 in the main study, however NO experimental therapy is being administered in this study. The intervention with Aflibercept IVT PRN in this study is NOT experimental.

Who Is Running the Clinical Trial?

Exegenesis Bio

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

In a clinical trial involving 46 patients with recalcitrant exudative age-related macular degeneration (AMD), treatment with 2.0 mg aflibercept maintained stable visual acuity, with no patients losing more than 15 letters on the ETDRS scale after 6 months.

Aflibercept treatment resulted in significant anatomical improvements, as evidenced by a reduction in central subfield thickness (CST), while most patients required monthly injections, indicating a high treatment demand.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Wykoff, CC., Brown, DM., Maldonado, ME., et al.[2022]

In a study of 60 patients receiving an average of 8.4 intravitreal injections of ziv-aflibercept over a mean follow-up of 9.2 months, significant improvements in best-corrected visual acuity (BCVA) and reductions in central macular thickness (CMT) were observed, indicating the treatment's efficacy for retinal disease.

The treatment was found to be safe, with no significant increases in intraocular pressure, no progression of lens opacities, and only one case of mild transient iritis, suggesting that repeated injections of ziv-aflibercept are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. Mansour, AM., Ashraf, M., Dedhia, CJ., et al.[2022]

Intravitreal aflibercept injection (IAI) demonstrated a safety profile comparable to control treatments across various retinal diseases, with no significant differences in rates of ocular and systemic adverse events among over 4000 patients in 10 clinical trials.

IAI was generally well tolerated, showing lower rates of intraocular inflammation and endophthalmitis compared to controls, indicating its efficacy and safety for treating conditions like neovascular age-related macular degeneration and diabetic macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. Kitchens, JW., Do, DV., Boyer, DS., et al.[2022]

In a study of 36 patients with neovascular age-related macular degeneration (AMD), aflibercept treatment resulted in a significant improvement in visual acuity, with a mean gain of nearly 16 letters after an average follow-up of 12 months.

The treatment was safe and effective, with 97.3% of patients maintaining their vision, and a decrease in central macular thickness, indicating a positive impact on the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of aflibercept therapy as a first line treatment of age-related macular degeneration. Unsal, E., Cubuk, MO.[2023]

In a study of 32 treatment-naïve patients with neovascular age-related macular degeneration (nvAMD), aflibercept significantly improved best-corrected visual acuity after 13 months, with 46.8% of patients gaining at least 15 letters on the ETDRS scale.

Aflibercept treatment also led to a significant reduction in central macular thickness and was well tolerated, with no adverse events reported, indicating its safety and efficacy in a real-life clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept as First-Line Therapy in Patients with Treatment-Naïve Neovascular Age-Related Macular Degeneration: Prospective Case Series Analysis in Real-Life Clinical Practice. Udaondo, P., Salom, D., García-Delpech, S., et al.[2017]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3539286/

Aflibercept in wet age-related macular degeneration

The results of the VEGF Trap-Eye: Investigation of Efficacy and Safety in wet Age-related Macular Degeneration studies (VIEW 1 and VIEW 2) support this by ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00637377

NCT00637377 | Vascular Endothelial Growth Factor (VEGF ...

This study is a phase III, double-masked, randomized, study of the efficacy and safety of VEGF Trap-Eye in patients with neovascular age-related macular ...

3.

nature.com

nature.com/articles/eye201781

Aflibercept in age-related macular degeneration

The recent VIEW studies have demonstrated the non-inferiority of monthly and bi-monthly aflibercept in the management of wet age related macular degeneration ( ...

4.

mdpi.com

mdpi.com/2077-0383/13/12/3503

Short-Term Real-World Outcomes of Intensive Aflibercept ...

Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response ...

5.

jamanetwork.com

jamanetwork.com/journals/jamaophthalmology/fullarticle/2807967

Effect of High-Dose Intravitreal Aflibercept, 8 mg, in ...

Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD).

6.

nature.com

nature.com/articles/s41598-024-65815-6

Comparison of the efficacy and safety of SCD411 ...

SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety ...

7.

aaojournal.org

aaojournal.org/article/S0161-6420(18)32031-1/fulltext

Safety and Efficacy of Anti-Vascular Endothelial Growth ...

To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular ...