4D-150 + EYLEA for Age-Related Macular Degeneration

Recruiting at 94 trial locations

Overseen By 4DMT Patient Advocacy

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: 4D Molecular Therapeutics

Disqualifiers: Retinal detachment, Glaucoma, Uncontrolled blood pressure, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A Phase 3, Randomized, Double-Masked, Active-Controlled Trial in Adults with Macular Neovascularization Secondary to Age-Related Macular Degeneration

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have glaucoma or intraocular hypertension, you should not be on more than two topical medications for control.

What data supports the effectiveness of the drug 4D-150 + EYLEA for age-related macular degeneration?

Research shows that EYLEA (aflibercept) is effective in treating age-related macular degeneration, as it has been used successfully in real-world settings to improve eye health in patients with this condition. ^{1 2 3 4 5}

Is 4D-150 + EYLEA safe for humans?

EYLEA (aflibercept) has been shown to have a good safety profile in treating various eye conditions like age-related macular degeneration and diabetic macular edema, with no major side effects reported in studies. ^{1 6 7 8 9}

What makes the drug 4D-150 unique for treating age-related macular degeneration?

4D-150 is unique because it is being studied in combination with Eylea, a well-known treatment for age-related macular degeneration, potentially offering a new approach to managing the condition. This combination could provide enhanced benefits compared to existing treatments alone. ^{1 2 4 10 11}

Research Team

Hersh Patel

Principal Investigator

4D Molecular Therapeutics

Eligibility Criteria

This trial is for adults over 50 with a specific eye condition called Macular Neovascularization due to Age-Related Macular Degeneration. Participants must have certain vision levels and be new to treatment. They can't join if they have glaucoma needing multiple drugs, recent heart or stroke issues, other causes of the eye condition, history of retinal detachment, autoimmune risks for uveitis, or major illness/surgery recently.

Inclusion Criteria

BCVA between 25 and 78 ETDRS letters, inclusive (20/320-20/32 Snellen equivalent) in the study eye at the Screening Visit

My eye condition has not been treated before.

My eye condition involves active abnormal blood vessels under the center of my retina.

Exclusion Criteria

I use more than 2 eye drops for glaucoma or high eye pressure.

I have or had eye inflammation.

I haven't had a heart attack or stroke in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of 4D-150 or Aflibercept

Single injection

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• 4D-150 (Virus Therapy)

Trial Overview The study compares two treatments: an experimental drug called 4D-150 given through injection into the eye versus EYLEA®, a standard treatment for this condition. It's a phase 3 trial where patients are randomly assigned to one of these treatments in a double-masked setup (neither doctors nor patients know who gets which).

Participant Groups

Group I: 4D-150 IVT (3E10 vg/eye) Experimental Treatment 1 Intervention

Group II: Aflibercept (AFLB) 2 mg IVT Active Control 1 Intervention

Who Is Running the Clinical Trial?

4D Molecular Therapeutics

Lead Sponsor

Trials

9

Recruited

850+

Findings from Research

In a study of 26 patients with neovascular age-related macular degeneration (nv-AMD), intravitreal injections of aflibercept (Eylea) led to a significant improvement in visual acuity over 14 months, with 61.5% of eyes showing improvement and a mean visual acuity change from 0.26 to 0.14 LogMAR (P=0.02).

The treatment also resulted in a significant reduction in central macular thickness from 409μm to 229μm (P<0.02), and no adverse events were reported, indicating that aflibercept is a safe and effective option for treating naïve patients with nv-AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. Papavasileiou, E., Zygoura, V., Richardson, T., et al.[2019]

In a study of 1017 patients treated with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD) over 4 years, 50% of patients maintained a vision level of 6/18 or better, indicating significant long-term efficacy of the treatment.

The average number of injections required increased over time, with patients receiving approximately 13.7 injections by the end of the 4-year period, highlighting the ongoing need for treatment and the importance of long-term follow-up in managing AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration. Pushpoth, S., Sykakis, E., Merchant, K., et al.[2015]

In a real-life study of 54 patients with wet age-related macular degeneration (ARMD), a treat-and-extend regimen with ranibizumab resulted in a mean visual acuity gain of 8.3 letters at 12 months and 5.2 letters at 24 months, indicating effective treatment over two years.

The study also showed significant anatomical improvements, with a mean reduction in central retinal thickness of 139.7 μm at 24 months, and a majority of patients (83.9%) either gained vision or maintained their baseline vision, demonstrating the regimen's efficacy and reduced treatment burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-month clinical outcomes of a treat-and-extend regimen with ranibizumab for wet age-related macular degeneration in a real life setting. Vardarinos, A., Gupta, N., Janjua, R., et al.[2018]

In a study of 94 eyes from 89 patients treated with intravitreal aflibercept for neovascular macular degeneration over 4 years, significant improvements in visual acuity were observed, with an average increase of 6.3 ETDRS letters (from 54.1 to 60.4 letters).

The treatment also led to a substantial reduction in central subfield macular thickness, indicating effective management of macular fluid, as 70% of eyes had no macular fluid by the end of the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting. Lukic, M., Eleftheriadou, M., Hamilton, RD., et al.[2022]

In the RAINBOW study, patients with neovascular age-related macular degeneration (nAMD) who received three initial monthly injections of intravitreal aflibercept (IVT-AFL) followed by regular treatments showed a significant improvement in visual acuity, with an average gain of +4.9 letters after 24 months.

Patients who did not receive the initial three doses and followed an irregular treatment schedule experienced a decline in visual acuity, highlighting the importance of consistent treatment regimens for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW. Weber, M., Dominguez, M., Coscas, F., et al.[2021]

In a study involving 30 patients with retinitis pigmentosa-associated cystoid macular oedema, intravitreal aflibercept (Eylea) was found to be safe, with no significant adverse events reported over 12 months.

While 37.9% of patients showed a reduction in central macular thickness (CMT) after treatment, there was no overall significant improvement in visual acuity, indicating that while some patients may benefit anatomically, this does not necessarily translate to better vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. Strong, SA., Peto, T., Bunce, C., et al.[2021]

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]

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 the 24-month HARBOR study involving 1095 participants with neovascular age-related macular degeneration (AMD), new macular atrophy (MA) was detected in 29.4% of eyes that did not have baseline atrophy, indicating a significant incidence of this condition during treatment.

Despite the presence of MA, participants experienced clinically significant gains in best-corrected visual acuity (BCVA), suggesting that the benefits of ranibizumab treatment for AMD may outweigh the risks associated with MA development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration. Sadda, SR., Tuomi, LL., Ding, B., et al.[2022]

In a study of 363 patients with chronic neovascular age-related macular degeneration, epimacular brachytherapy (EMB) did not reduce the number of anti-VEGF injections needed compared to ranibizumab monotherapy, indicating no added benefit in treatment frequency.

Over 36 months, patients receiving EMB experienced a significant decline in best-corrected visual acuity (BCVA) compared to those on ranibizumab alone, suggesting that EMB may be less effective in preserving vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. Jackson, TL., Soare, C., Petrarca, C., et al.[2023]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (A-IVI) for the treatment of neovascular age-related macular degeneration (nv-AMD): one year experience. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration. [2015]

3. England pubmed.ncbi.nlm.nih.gov

24-month clinical outcomes of a treat-and-extend regimen with ranibizumab for wet age-related macular degeneration in a real life setting. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Four-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Results from real-life setting. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for neovascular age-related macular degeneration. [2022]

9. Romania pubmed.ncbi.nlm.nih.gov

[Preliminary results of treatment with aflibercept]. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. [2023]