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

Phase 2
Completed
Conditions
Retinal Degeneration
Edema
Diabetic Macular Edema
Macular Edema
Diabetic Retinopathy
Eye Diseases
Retinal Disease
Diabetes Mellitus
Retinal Diseases
Interventions
Registration Number
NCT06011798
Lead Sponsor
Unity Biotechnology, Inc.
Brief Summary

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

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 50 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 36 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Anti-VEGF control armAfliberceptPrior 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.
foselutoclax armAfliberceptPrior 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.
foselutoclax armfoselutoclaxPrior 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.
Primary Outcome Measures
NameTimeMethod
Mean Change From Baseline to Average of Week 20 and Week 24 in BCVA by ETDRS LetterWeek 24

Mean change from baseline to the average of Week 20 and Week 24 in Best-Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter

Secondary Outcome Measures
NameTimeMethod
Assess Safety Outcome - Safety and Tolerability36 weeks

Number of participants with treatment-emergent adverse event (TEAE)

Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 3636 weeks

Changes in BCVA (ETDRS letters) from baseline to Week 36

Assess Other Efficacy Outcome - Changes in CST From Baseline to Week 3636 weeks

Change in Central Subfield Thickness (CST) as measured in microns from baseline to Week 36

Assess Other Efficacy Outcome - Rescue Metrics36 weeks

At any visit, including Unscheduled visits, patients who exhibited increase in disease activity, were allowed to be rescued with aflibercept. Increase in disease activity was defined as ANY of the following:

* Worsening CST by ≥75 µm from baseline per SD-OCT

* A ≥10 letter decrease in BCVA compared to baseline

* New clinically significant blood or heme present compared to previous visit

* PI discretion (rationale to be documented in the EDC)

Ocular Safety and Tolerability36 weeks

Ocular Safety is evaluated by incidence of ocular Treatment Emergent Adverse Events (TEAEs).

Trial Locations

Locations (19)

California Retina Consultants

🇺🇸

Bakersfield, California, United States

Retina-Vitreous Associates Medical Group

🇺🇸

Beverly Hills, California, United States

Salehi Retina Institute Inc.

🇺🇸

Huntington Beach, California, United States

Bay Area Retina Associates

🇺🇸

Walnut Creek, California, United States

Advanced Vision Research Institute

🇺🇸

Longmont, Colorado, United States

Rand Eye Institute

🇺🇸

Deerfield Beach, Florida, United States

Florida Eye Associates

🇺🇸

Melbourne, Florida, United States

Retina Vitreous Associates of Florida

🇺🇸

Saint Petersburg, Florida, United States

University Retina and Macula Associates

🇺🇸

Lemont, Illinois, United States

Midwest Eye

🇺🇸

Carmel, Indiana, United States

Scroll for more (9 remaining)
California Retina Consultants
🇺🇸Bakersfield, California, United States

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