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

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

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

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Diabetes Mellitus; Retinal Degeneration; Retinal Diseases; Edema; Diabetic Retinopathy; Diabetic Macular Edema; Macular Edema; Retinal Disease
• Intervention / Treatment: Drug: Aflibercept; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Huntington Beach, California, United States, 92647
      • Salehi Retina Institute Inc.
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Colorado
    • Longmont, Colorado, United States, 80503
      • Advanced Vision Research Institute
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Rand Eye Institute
    • Melbourne, Florida, United States, 32901
      • Florida Eye Associates
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Associates of Florida
  • Illinois
    • Lemont, Illinois, United States, 60439
      • University Retina and Macula Associates
  • Indiana
    • Carmel, Indiana, United States, 46290
      • Midwest Eye
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Oregon
    • Portland, Oregon, United States, 97225
      • EyeHealth Northwest
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research, LLC
    • Philadelphia, Pennsylvania, United States, 19141
      • Vision Research Solutions, PLLC
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Retina Consultants of Carolina
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institution of Texas
    • Round Rock, Texas, United States, 78681
      • Austin Retina Associates
    • Southlake, Texas, United States, 76092
      • Retina Center Of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anti-VEGF control arm; 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; Anti-VEGF control
Experimental: foselutoclax arm; 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; Anti-VEGF control; Drug: foselutoclax; Experimental drug; Other Names: UBX1325

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Average of Week 20 and Week 24 in BCVA by ETDRS Letter	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	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 36	Changes in BCVA (ETDRS letters) from baseline to Week 36	36 weeks
Assess Other Efficacy Outcome - Changes in CST From Baseline to Week 36	Change in Central Subfield Thickness (CST) as measured in microns from baseline to Week 36	36 weeks
Assess Other Efficacy Outcome - Rescue Metrics	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)	36 weeks
Assess Safety Outcome - Safety and Tolerability	Number of participants with treatment-emergent adverse event (TEAE)	36 weeks
Ocular Safety and Tolerability	Ocular Safety is evaluated by incidence of ocular Treatment Emergent Adverse Events (TEAEs).	36 weeks

Collaborators and Investigators

• Sponsor: Unity Biotechnology, Inc.
• Investigators: Study Director: Robert Bhisitkul, MD, Ph.D., Unity Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2023
• Primary Completion (Actual): January 21, 2025
• Study Completion (Actual): April 8, 2025

Study Registration Dates

• First Submitted: August 2, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: DME
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Eye Diseases, Hereditary; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Eye Diseases; Retinal Degeneration; Edema; Macular Edema; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: UBX1325-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No