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

Recruiting at 108 trial locations

Overseen By 4DMT Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: 4D Molecular Therapeutics

Disqualifiers: Retinal detachment, Glaucoma, Uncontrolled blood pressure, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Single injection

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 4D-150 for age-related macular degeneration (AMD), which can cause vision loss due to abnormal blood vessels in the eye. Researchers aim to determine if 4D-150, an experimental treatment, manages this condition better than the current treatment, EYLEA (Aflibercept). Participants will receive either the new treatment or EYLEA to compare their effectiveness. The trial seeks individuals who have not received treatment for AMD and have specific signs of active AMD affecting their central vision. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to advancing AMD treatment.

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.

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

Research has shown that 4D-150 is generally safe for people. In previous studies, patients handled 4D-150 well. Notably, no reports of eye inflammation occurred at any dose, indicating the treatment did not cause serious irritation or swelling in the eyes. These studies also found 4D-150 safe at all dose levels, from low to high. This strong evidence supports the belief that 4D-150 is safe for use in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 4D-150 because it offers a novel approach to treating age-related macular degeneration. Unlike standard treatments like anti-VEGF injections that need frequent administration, 4D-150 uses gene therapy to provide a potentially longer-lasting effect from a single injection. This treatment delivers genetic material directly into the eye to help it produce its own anti-VEGF proteins, potentially reducing the need for regular injections and improving patient convenience and compliance. Additionally, combining 4D-150 with EYLEA could enhance treatment effectiveness, offering a powerful new option for patients.

What evidence suggests that this trial's treatments could be effective for age-related macular degeneration?

Studies have shown that 4D-150, one of the treatments tested in this trial, consistently benefits patients with wet age-related macular degeneration (AMD). Research indicates it helps maintain clear vision and reduces the need for additional eye injections over time. 4D-150 is designed to deliver a long-lasting treatment that blocks a protein responsible for abnormal blood vessel growth in the eye. This treatment has been well-tolerated and does not cause eye inflammation. Initial findings suggest this approach can offer a lasting solution for managing vision problems related to wet AMD. Participants in this trial may receive either 4D-150 or the active comparator, Aflibercept (AFLB). ^{1 2 3 6 7}

Who Is on the Research Team?

Hersh Patel

Principal Investigator

4D Molecular Therapeutics

Are You a Good Fit for This Trial?

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.

My vision loss is not due to wet age-related macular degeneration.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 4D-150

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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 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]

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]

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 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]

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 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]

Citations

1. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-positive-long-term-data-phase-12-prism-clinical

Release Details 4D-150 demonstrated consistent and durable benefit across all three patient cohorts as evidenced by maintenance of visual acuity, ...

2. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-presents-positive-60-week-results-4d-150-spectra-clinical

4DMT Presents Positive 60-Week Results from 4D-150 ... 4D-150 continues to be well tolerated with no intraocular inflammation observed at any timepoint or dose level; 4D-150 demonstrated durable ...

3. ophthalmologytimes.com ophthalmologytimes.com/view/4dmt-releases-positive-interim-1-5--to-3-5-year-data-from-phase-1-2-prism-trial

4DMT releases positive interim 1.5- to 3.5-year data from ... 4D-150 demonstrated sustained anti-VEGF delivery, improving visual acuity and reducing supplemental injections in wet AMD patients over 1.5 to ...

4. 4dmt.gcs-web.com 4dmt.gcs-web.com/news-releases/news-release-details/4dmt-announces-accelerated-4d-150-phase-3-development-wet-amd

4DMT Announces Accelerated 4D-150 Phase 3 Development ... 4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06864988

Study Details | NCT06864988 | 4D-150 in Patients With ... Study Details | NCT06864988 | 4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration | ClinicalTrials.gov.

6. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2789669

Phase 1/2 PRISM Trial: 4D-150 for Wet AMD 4D-150 was safe and well tolerated at doses ranging from 6×10 9 to 3×10 10 vg/eye. Encouraging evidence of clinical activity was observed.

7. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-highlights-robust-and-durable-clinical-activity-4d-150-and

4DMT Highlights Robust and Durable Clinical Activity for ... “Based on the data to date, 4D-150 has the potential to decrease treatment burden and control wet AMD with a safe, single routine intravitreal ...