Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the efficacy and safety of multiple doses of foselutoclax (UBX1325) in patients with Diabetic Macular Edema. The main questions the study aims to answer are: Assess the efficacy of foselutoclax compared to aflibercept Assess the safety and tolerability of foselutoclax

Detailed Description
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This study is intended to assess the efficacy and safety of foselutoclax , a phosphate pro-drug, and its active parent molecule (UBX0601, a BCL-xL inhibitor) following repeat intravitreal (IVT) injections of foselutoclax in patients with Diabetic Macular Edema (DME). Approximately 40 patients will be enrolled and randomized 1:1 into either the foselutoclax arm,10 μg given 8 weeks apart, or the control arm of aflibercept, 2 mg every 8 weeks in order to assess the primary objective. All patients will be followed for approximately 24 weeks. The injector will be unmasked but the evaluator will remain masked throughout the study. This study will enroll participants ≥18 years of age with active DME disease despite treatment, with best corrected visual acuity (BCVA) between 70 to 30 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (equivalent to 20/40 to 20/250 on the Snellen chart). Once patients meet inclusion/exclusion criteria, patients will receive 3 run-in injections of aflibercept approximately 4 weeks apart, with the last aflibercept injection 4-6 weeks prior to Day 1.

Official Title
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A Phase 2b, Prospective, Multicenter, Randomized, Double-Masked, Active-Controlled Study to Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema, Retinal Disease, Macular Edema, Diabetes Mellitus, Diabetic Retinopathy, Retinal Degeneration, Retinal Diseases, Eye Diseases, Edema

Intervention / Treatment
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* Drug: Aflibercept
* Drug: foselutoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18 years. Patients with nonproliferative DR and DME Center-involved DME with Central Subfield Thickness (CST) ≥325-900 μm BCVA in the SE (most affected) of 70 to 30 ETDRS letters (equivalent to 20/40 to 20/250 on the Snellen chart) Exclusion Criteria: Concurrent disease in the study eye (SE) or structural damage, other than DME, that could compromise BCVA, prevent BCVA improvement, require medical or surgical intervention during the study period, confound interpretation of the results, or interfere with assessment of toxicity or Color Fundus Photography (CFP) in the SE. Significant media opacities, including cataract, or posterior capsule opacification, which might interfere with VA, assessment of toxicity, or fundus imaging in either eye. Any medical condition that is uncontrolled and may prevent participation in this study, as determined by the Investigator or disqualify individuals from enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anti-VEGF control arm<br>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. | Drug: Aflibercept<br>* Anti-VEGF control<br>|
| Experimental: foselutoclax arm<br>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. | Drug: Aflibercept<br>* Anti-VEGF control<br>Drug: foselutoclax<br>* Experimental drug<br>* Other names: UBX1325;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in BCVA by ETDRS letter | Mean change from baseline in Best-Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess other efficacy outcome - Changes in BCVA | Changes in BCVA (ETDRS letters) from baseline to visits prior to Week 24 | 24 weeks | 
| Assess other efficacy outcome - Changes in CST | Change in Central Subfield Thickness (CST) as measured in microns from baseline to Week 24 | 24 weeks | 
| Assess other efficacy outcome - ETDRS gains | Proportion of participants gaining ≥15, ≥10, ≥5, or ≥0 ETDRS letters in BCVA from baseline in the Study Eye (SE) to week 24 | 24 weeks | 
| Assess safety outcome - TEAE | Percentage of participants with at least one treatment-emergent ocular adverse event (AE) in the SE or Fellow Eye (FE) | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME