Foselutoclax for Diabetic Macular Edema

(ASPIRE Trial)

Recruiting at 20 trial locations

Overseen By Roger A Goldberg, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Biotechnology, Inc.

Disqualifiers: Concurrent eye disease, Cataract, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 39

Duration: 16 weeks

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing foselutoclax, a new drug, in patients with Diabetic Macular Edema who haven't responded to other treatments. The drug works by blocking a protein to reduce eye swelling and improve vision.

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

What data supports the effectiveness of the drug Foselutoclax for Diabetic Macular Edema?

Research shows that Aflibercept (Eylea), a component of the treatment, significantly improves vision in patients with diabetic macular edema compared to other treatments. Studies have demonstrated better visual outcomes and reduced macular thickness, indicating its effectiveness in managing this condition. ^{1 2 3 4 5}

Is Foselutoclax (Aflibercept/Eylea) safe for humans?

Aflibercept (also known as Eylea) has been generally well tolerated in clinical trials for conditions like diabetic macular edema and macular edema due to central retinal vein occlusion, with no major side effects reported. ^{1 2 3 6 7}

How is the drug Foselutoclax (Aflibercept) unique for treating diabetic macular edema?

Foselutoclax (Aflibercept) is unique because it acts as a decoy receptor for vascular endothelial growth factor (VEGF), which helps reduce fluid leakage and swelling in the eye, improving vision. It binds VEGF with higher affinity than similar drugs like ranibizumab or bevacizumab, potentially offering better outcomes for patients with diabetic macular edema. ^{1 2 4 5 6}

Research Team

Robert Bhisitkul, MD, Ph.D

Principal Investigator

Unity Biotechnology, Inc.

Eligibility Criteria

This trial is for adults over 18 with nonproliferative diabetic retinopathy and diabetic macular edema. Participants must have a certain level of central retina thickness and vision range. Those with other eye conditions, significant cataracts, or uncontrolled medical issues that could affect the study are not eligible.

Inclusion Criteria

I have non-growing diabetic retinopathy and swelling in my retina.

My eye condition involves swelling in the center of my retina.

Your vision in your most affected eye is between 20/40 and 20/250 on the eye chart.

Exclusion Criteria

I have eye conditions like cataracts that could affect my vision or eye exams.

My study eye has no other conditions or damage that could affect vision improvement.

Any medical condition that is uncontrolled and may prevent participation in this study, as determined by the Investigator or disqualify individuals from enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants receive 3 intravitreal injections of aflibercept approximately 4 weeks apart before randomization

12 weeks

Treatment

Participants receive either foselutoclax or aflibercept intravitreal injections on Day 1, Weeks 8, and 16

16 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Regular visits through Week 36

Treatment Details

Interventions

• Aflibercept
• Foselutoclax

Trial Overview The trial tests the effectiveness and safety of foselutoclax (UBX1325) injections in comparison to aflibercept for treating diabetic macular edema. It aims to determine if foselutoclax can improve patients' vision better or as well as aflibercept while monitoring any side effects.

Participant Groups

Group I: foselutoclax arm Experimental Treatment 2 Interventions

Prior to randomization, participants will receive 3 IVT injections of aflibercept over 4-week intervals. Upon randomization, participants will receive 10 μg foselutoclax (50 μl of 0.2 μg/μl solution) IVT on Day 1 and Weeks 8 and 16. 2 mg aflibercept (50 μl of 40 μg/μl solution) will also be administered on Day 1.

Group II: Anti-VEGF control arm Active Control 1 Intervention

Prior to randomization, participants will receive 3 IVT injections of aflibercept over 4-week intervals. Upon randomization, participants will receive 2 mg aflibercept (50 μl of 40 μg/μl solution) IVT on Day 1, Weeks 8, and 16. A sham procedure will also be administered on Day 1.

Aflibercept is already approved in United States, European Union for the following indications:

Approved in United States as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

Approved in European Union as Eylea for:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR)

Approved in United States as Zaltrap for:

• Metastatic Colorectal Cancer

Who Is Running the Clinical Trial?

Unity Biotechnology, Inc.

Lead Sponsor

Trials

9

Recruited

670+

Findings from Research

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]

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 of 30 eyes from 23 patients with diabetic macular edema (DME) who previously received an average of 16 injections of ranibizumab and/or bevacizumab, switching to aflibercept resulted in a significant reduction in central subfoveal thickness, improving from 374 µm to 332 µm after the first aflibercept injection (P < .001).

Visual acuity also improved after the switch to aflibercept, with a change from logMAR 0.40 (20/50) to logMAR 0.35 (20/45) (P = .044), suggesting that aflibercept may be a beneficial treatment option for patients with persistent DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept for Diabetic Macular Edema in Eyes Previously Treated With Ranibizumab and/or Bevacizumab May Further Improve Macular Thickness. Shah, CP., Heier, JS.[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]

In a study of 90 eyes from 67 patients switched from ranibizumab to aflibercept for diabetic macular edema, there was a significant improvement in visual acuity, with an average increase of 4 Early Treatment Diabetic Retinopathy Study letters after 12 months (p=0.0053).

Anatomical outcomes also showed positive trends, with a reduction in central foveal thickness by 136.8 μm, although this change was not statistically significant (p=0.69), indicating that aflibercept may be effective in improving vision in patients previously treated with ranibizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab. Lukic, M., Williams, G., Shalchi, Z., et al.[2021]

Aflibercept, a recombinant fusion protein, effectively inhibits VEGF signaling and has been shown to significantly improve visual acuity in patients with macular edema due to central retinal vein occlusion (CRVO) when administered intravitreally at a dose of 2 mg monthly, as demonstrated in clinical trials with significant improvements over sham injections.

The treatment was generally well tolerated with minimal risk of systemic drug accumulation, making aflibercept a safe and effective option for managing CRVO-related macular edema, although optimal monitoring strategies for long-term efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. Yang, LP., McKeage, K.[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]

References

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

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

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

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

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

Aflibercept for Diabetic Macular Edema in Eyes Previously Treated With Ranibizumab and/or Bevacizumab May Further Improve Macular Thickness. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

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

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

One-year real-life results on effect of intravitreal aflibercept in patients with diabetic macular oedema switched from ranibizumab. [2021]

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

Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. [2021]

7. Romania pubmed.ncbi.nlm.nih.gov

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