4D-150 for Diabetic Macular Edema

Recruiting at 15 trial locations

Overseen By Chyong N

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: 4D Molecular Therapeutics

Must be taking: Aflibercept

Must not be taking: Anti-VEGF, Corticosteroids

Disqualifiers: Macular edema, Gene therapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

72 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic anti-VEGF treatments and systemic corticosteroids or other immunosuppressive medications before participating. If you are on these medications, you will need to stop them for a certain period before joining the trial.

What data supports the effectiveness of the drug 4D-150 IVT for treating diabetic macular edema?

Research shows that aflibercept (Eylea), a component of 4D-150 IVT, significantly improves vision in patients with diabetic macular edema compared to other treatments. Studies have demonstrated its effectiveness in improving visual acuity and reducing eye swelling over time. ^{1 2 3 4 5}

Is 4D-150 safe for humans?

Studies on similar treatments like aflibercept (Eylea) and ziv-aflibercept (Zaltrap) for conditions such as diabetic macular edema and retinitis pigmentosa have shown that these treatments are generally safe, with some patients experiencing mild side effects like eye discomfort or increased eye pressure. ^{1 3 5 6 7}

What makes the drug 4D-150 IVT unique for treating diabetic macular edema?

4D-150 IVT is unique because it combines aflibercept, a well-known anti-vascular endothelial growth factor (anti-VEGF) drug, with a novel approach that may enhance its effectiveness in treating diabetic macular edema. This combination could potentially offer improved outcomes compared to standard treatments like macular laser photocoagulation or other anti-VEGF drugs. ^{1 2 3 5 8}

Research Team

Schonmei Lee, MD

Principal Investigator

4D Molecular Therapeutics

Eligibility Criteria

Adults over 18 with Diabetic Macular Edema (DME) diagnosed within the last two years, who've shown improvement after an aflibercept eye injection. Participants must have certain levels of vision in the affected eye and be able to undergo further injections. Those with other causes for macular edema or on recent anti-VEGF/corticosteroid treatments can't join.

Inclusion Criteria

My eye condition improved after receiving an aflibercept injection.

Provide written informed consent

My eyes are healthy enough for detailed exams and tests.

Exclusion Criteria

My eye condition may need surgery within the next 2 years.

My macular edema is not due to diabetic macular edema.

I haven't taken any experimental treatments in the last 3 months or 5 half-lives, whichever is longer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation

Participants receive a single dose IVT injection of 4D-150 at the assigned dose level on Day 1

1 day

1 visit (in-person)

Dose Expansion

Participants receive a single dose IVT injection of 4D-150 at the assigned dose level on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• 4D-150 IVT
• Aflibercept

Trial Overview The trial is testing a new treatment called 4D-150 compared to Aflibercept, both administered through an injection into the eye (IVT). It's designed to see which is better at improving vision for people with DME. Patients are randomly assigned to receive one of these treatments and won't know which they're getting.

Participant Groups

Group I: 4D-150 Part 2 Dose Expansion Dose Level 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 II: 4D-150 Part 2 Dose Expansion Dose Level 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 III: 4D-150 Part 1 Dose Confirmation Dose Level 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 IV: 4D-150 Part 1 Dose Confirmation Dose Level 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 V: 4D-150 Part 2 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

Intravitreal aflibercept significantly improved visual acuity in patients with diabetic macular oedema compared to macular laser photocoagulation and other treatments like bevacizumab and ranibizumab, particularly in those with worse baseline vision, as shown in phase III trials.

Aflibercept was generally well tolerated, making it a promising and effective new treatment option for diabetic macular oedema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept: A Review of Its Use in Diabetic Macular Oedema. Keating, GM.[2022]

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]

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 of 92 diabetic patients treated with intravitreal aflibercept for diabetic macular edema, significant improvements were observed after 12 months, with average visual acuity increasing from 59.7 to 69.6 Early Treatment Diabetic Retinopathy Study letters.

Aflibercept treatment also led to a notable reduction in central foveal thickness from 431 µm to 306 µm, indicating effective anatomical changes alongside improved vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes. Lukic, M., Williams, G., Shalchi, Z., 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]

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 26 patients with refractory diabetic macular edema (DME), ziv-aflibercept treatment led to significant improvements in visual acuity and macular thickness after switching from previous anti-VEGF therapies.

No adverse ocular or systemic side effects were reported, indicating that ziv-aflibercept is a safe option for patients who did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. Ashraf, M., Kayal, HE., Souka, AAR.[2022]

Intravitreal aflibercept (IVT-AFL) treatment significantly improved best-corrected visual acuity (BCVA) in both treatment-naïve patients (+7.8 letters) and previously treated patients (+5.0 letters) after 12 months, indicating its efficacy in managing diabetic macular edema (DME).

The treatment also led to a decrease in central retinal thickness (CRT) in both groups, with a consistent injection frequency of about 7.6 injections over the year, although 54.1% of patients experienced ocular treatment-emergent adverse events, highlighting the need for monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. Korobelnik, JF., Daien, V., Faure, C., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Aflibercept: A Review of Its Use in Diabetic Macular Oedema. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

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

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

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

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

Intravitreal aflibercept for diabetic macular oedema: Moorfields' real-world 12-month visual acuity and anatomical outcomes. [2022]

5. 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]

6. 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]

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

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. [2020]