4D-150 for Age-Related Macular Degeneration

Recruiting at 20 trial locations

Overseen By Joel Pearlman, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: 4D Molecular Therapeutics

Must be taking: Anti-VEGF

Disqualifiers: Uveitis, Photodynamic therapy, others

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

Compensation: Varies

Number of Visits: 28

215 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you continue receiving anti-VEGF treatment in the study eye.

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

Research shows that similar drugs like aflibercept (Eylea) and ziv-aflibercept (Zaltrap) have been effective in improving vision and reducing fluid in the eyes of patients with age-related macular degeneration, suggesting potential effectiveness for 4D-150 IVT as well. ^{1 2 3 4 5}

Is 4D-150 safe for humans?

Research on similar treatments like ziv-aflibercept and aflibercept (Eylea) shows they are generally safe for eye conditions like age-related macular degeneration and diabetic macular edema, with no adverse events reported in short-term studies. ^{1 2 4 5 6}

How is the drug 4D-150 IVT different from other treatments for age-related macular degeneration?

4D-150 IVT is unique because it combines aflibercept, a drug that helps reduce abnormal blood vessel growth in the eye, with a novel approach that may offer improved outcomes for patients who do not respond well to other treatments like bevacizumab and ranibizumab. ^{1 2 3 5 6}

What is the purpose of this trial?

Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment. Substudies will evaluate the safety and tolerability of 4D-150 contralateral eye dosing and characterize vector shedding.

Research Team

Jennifer Lee, MD

Principal Investigator

4D Molecular Therapeutics

Eligibility Criteria

This trial is for adults over 50 with wet Age-Related Macular Degeneration (AMD) who have been treated with at least 6 anti-VEGF injections in the past year and shown improvement. They should have a certain level of vision, not worse than ~20/320. Those with central fovea damage, history of uveitis, or previous specific eye treatments are excluded.

Inclusion Criteria

I am 50 years old or older.

I am being treated with anti-VEGF for my eye and it's working.

BCVA ETDRS Snellen equivalent for dose escalation between ~20/32 and ~20/320, or for dose expansion and population extension between ~20/25 and~20/200, for steroid optimization between ~20/25 and ~20/640

Exclusion Criteria

I have had photodynamic therapy or retinal laser treatment in my study eye.

I have a condition that stops my vision from getting better in one eye.

I do not have eye conditions that would affect my participation in a study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive a single dose of 4D-150 by intravitreal injection at assigned dose levels

1 day

1 visit (in-person)

Dose Expansion

Participants receive a single dose of 4D-150 by intravitreal injection at assigned dose levels

1 day

1 visit (in-person)

Steroid Optimization

Participants receive a single dose of 4D-150 by intravitreal injection with steroid optimization

1 day

1 visit (in-person)

Population Extension

Participants receive a single dose of 4D-150 by intravitreal injection at assigned dose levels

1 day

1 visit (in-person)

Follow-up

Participants undergo monthly assessments for safety and efficacy outcomes

24 months

24 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and duration of clinical activity of 4D-150 gene therapy

60 months

Treatment Details

Interventions

• 4D-150 IVT
• Aflibercept IVT

Trial Overview The study tests two intravitreal treatments: Aflibercept (an existing drug) and an experimental drug called 4D-150 for wet AMD. It's a Phase 1/2 trial that starts by finding safe doses and then compares the drugs' effects in a controlled setup where participants don't know which treatment they're getting.

Participant Groups

Group I: 4D-150 Vector Shedding Dose Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group II: 4D-150 Steroid Optimization Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group III: 4D-150 Population Extension Dose 3 Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose

Group IV: 4D-150 Population Extension Dose 2 Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group V: 4D-150 Population Extension Dose 1 Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group VI: 4D-150 Dose Expansion Dose 2 Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group VII: 4D-150 Dose Expansion Dose 1 Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group VIII: 4D-150 Dose Escalation up to 4 dose levels Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group IX: 4D-150 Contralateral Eye Dose Experimental Treatment 1 Intervention

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group X: 4D-150 Dose Expansion Control Active Control 1 Intervention

Aflibercept at a fixed regimen will be administered.

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]

A patient with exudative age-related macular degeneration showed significant improvement in visual acuity and reduction of fluid after receiving an intravitreal injection of ziv-aflibercept, indicating its efficacy in treating this condition.

The treatment was well-tolerated with no adverse events reported, demonstrating both short-term safety and effectiveness in managing neovascular macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. de Oliveira Dias, JR., Xavier, CO., Maia, A., et al.[2015]

In a study of 16 eyes from 14 patients with neovascular age-related macular degeneration (nAMD) who did not respond to previous treatments, switching to intravitreal ziv-aflibercept (IVZ) therapy resulted in a longer treatment-free interval, averaging 114.4 days compared to 76.3 days before the switch.

Despite the increased treatment-free interval, there was no significant improvement in best corrected visual acuity (BCVA) or other anatomical measures after 12 months of IVZ therapy, with 50% of eyes experiencing a decline in vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration. Braimah, IZ., Agarwal, K., Mansour, A., et al.[2018]

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]

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]

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]

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

Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration. [2015]

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

One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration. [2018]

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

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]

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

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes. [2019]

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]