Safety, Tolerability and Evidence of Activity Study of UBX1325 in Patients With Diabetic Macular Edema (BEHOLD)

Study Overview
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Brief Summary
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This study is intended to assess the exposure, safety, biological activity, and durability of UBX1325, a phosphate pro-drug, and its active parent molecule (UBX0601) following a single intravitreal (IVT) injection of UBX1325 in patients with diabetic macular edema (DME).

Detailed Description
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This is a Phase 2a Proof-of-Concept (POC) study. The study will enroll approximately 62 patients randomized 1:1 into either the UBX1325 or sham study arms, in order to assess safety and tolerability as well as impact on visual function and retinal anatomy. Patients will be followed for 24 weeks for the primary outcome measure and for an additional 24 weeks (48 weeks total) for the secondary outcome measures.

Official Title
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A Phase 2a, Prospective, Multicenter, Randomized, Double Masked, Sham-Controlled Study to Assess the Safety, Tolerability and Evidence of Activity of a Single Intravitreal Injection of UBX1325 in Patients With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema (DME)

Intervention / Treatment
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* Drug: UBX1325
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years. Diabetic retinopathy patients (nonproliferative (NPDR) and proliferative (PDR)) with DME (ETDRS-DRSS Score at 65C [or DR severity level of 8]or less severe as determined by a Central Reading Center), who had at least 2 anti-VEGF intravitreal (IVT) injections (one or more of the following agents: aflibercept, bevacizumab or ranibizumab) in the preceding 6 months prior to Day 1, with the last anti-VEGF given between 3 and 6 weeks prior to Day 1. Center-involved DME with central subfield thickness (CST) ≥300 µm on SD-OCT at Screening BCVA in the study eye (most affected) of 73 to 20 ETDRS letters (equivalent to 20/40 to 20/400 on the Snellen chart) at Screening and at Day 1. Exclusion Criteria: Concurrent disease in the study eye 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 study eye. Any ocular/intraocular/periocular infection or inflammation in either eye in the past 4 weeks prior to screening History of vitreous hemorrhage in the study eye within 2 months prior to Screening Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation or prevent the patient from fully participating in all aspects of the study Significant media opacities, including cataract, which might interfere with VA, assessment of toxicity, or fundus imaging

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UBX1325<br> | Drug: UBX1325<br>* Patients will be administered a single 50 μL UBX1325 IVT injection<br>|
| Sham Comparator: Sham Control<br> | Other: Sham<br>* Sham procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular and systemic safety and tolerability of a single IVT injection of UBX1325 evaluated by incidence of treatment emergent adverse events (TEAEs) |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in best corrected visual acuity (BCVA) from Baseline |  | Week 12, 24 and 48 | 
| Proportion of patients who require 2 or more anti-VEGF rescue |  | Week 12, 24 and 48 | 
| Change in central subfield thickness (CST) from baseline to each study visit as assessed by spectral domain optical coherence tomography (SD-OCT) |  | Week 12, 24 and 48 | 
| Change in CST area under the curve (AUC) from baseline to each study visit |  | Week 12, 24 and 48 | 
| Proportion of patients without macular fluid as assessed by SD-OCT |  | Week 12, 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinal disease, Macular edema, Diabetes mellitus, Diabetic macular edema