Diabetes Mellitus, Diabetic Macular Edema, Diabetic Retinopathy, Edema, Eye Diseases, Macular Edema, Retinal Degeneration, Retinal Disease, Retinal Diseases
Conditions
Keywords
DME
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.
Interventions
DRUGAflibercept
Anti-VEGF control
DRUGfoselutoclax
Experimental drug
Sponsors
Unity Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Average of Week 20 and Week 24 in BCVA by ETDRS Letter | Week 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
| Measure | Time frame | Description |
|---|---|---|
| Ocular Safety and Tolerability | 36 weeks | Ocular Safety is evaluated by incidence of ocular Treatment Emergent Adverse Events (TEAEs). |
| Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 36 | 36 weeks | Changes in BCVA (ETDRS letters) from baseline to Week 36 |
| Assess Other Efficacy Outcome - Changes in CST From Baseline to Week 36 | 36 weeks | Change in Central Subfield Thickness (CST) as measured in microns from baseline to Week 36 |
| Assess Other Efficacy Outcome - Rescue Metrics | 36 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) |
| Assess Safety Outcome - Safety and Tolerability | 36 weeks | Number of participants with treatment-emergent adverse event (TEAE) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Aflibercept: Anti-VEGF control | 26 |
| 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.
Aflibercept: Anti-VEGF control
foselutoclax: Experimental drug | 26 |
| Total | 52 |
Baseline characteristics
| Characteristic | Foselutoclax Arm | Total | Anti-VEGF Control Arm |
|---|---|---|---|
| Age, Continuous | 66.2 years STANDARD_DEVIATION 7.57 | 66.1 years STANDARD_DEVIATION 8.09 | 65.9 years STANDARD_DEVIATION 8.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 45 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 22 Participants | 43 Participants | 21 Participants |
| Sex: Female, Male Female | 9 Participants | 17 Participants | 8 Participants |
| Sex: Female, Male Male | 17 Participants | 35 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 2 / 26 | 0 / 26 | 15 / 26 | 22 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 5 / 26 | 5 / 26 |
Outcome results
Primary
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
Time frame: Week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anti-VEGF Control Arm | Mean Change From Baseline to Average of Week 20 and Week 24 in BCVA by ETDRS Letter | 5.1 change in ETDRS letters | Standard Error 1.35 |
| Foselutoclax Arm | Mean Change From Baseline to Average of Week 20 and Week 24 in BCVA by ETDRS Letter | 3.7 change in ETDRS letters | Standard Error 1.36 |
Secondary
Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 36
Changes in BCVA (ETDRS letters) from baseline to Week 36
Time frame: 36 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anti-VEGF Control Arm | Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 36 | 4.7 change in ETDRS letters | Standard Error 1.63 |
| Foselutoclax Arm | Assess Other Efficacy Outcome - Changes in BCVA From Baseline to Week 36 | 4.6 change in ETDRS letters | Standard Error 1.59 |
Secondary
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
Time frame: 36 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Anti-VEGF Control Arm | Assess Other Efficacy Outcome - Changes in CST From Baseline to Week 36 | 9.2 microns | Standard Error 23.69 |
| Foselutoclax Arm | Assess Other Efficacy Outcome - Changes in CST From Baseline to Week 36 | -1.9 microns | Standard Error 23.33 |
Secondary
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)
Time frame: 36 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anti-VEGF Control Arm | Assess Other Efficacy Outcome - Rescue Metrics | No Rescues | 61.5 percentage of participants |
| Anti-VEGF Control Arm | Assess Other Efficacy Outcome - Rescue Metrics | 1 Rescue | 23.1 percentage of participants |
| Anti-VEGF Control Arm | Assess Other Efficacy Outcome - Rescue Metrics | > = 2 Rescues | 15.4 percentage of participants |
| Foselutoclax Arm | Assess Other Efficacy Outcome - Rescue Metrics | No Rescues | 34 percentage of participants |
| Foselutoclax Arm | Assess Other Efficacy Outcome - Rescue Metrics | 1 Rescue | 34.6 percentage of participants |
| Foselutoclax Arm | Assess Other Efficacy Outcome - Rescue Metrics | > = 2 Rescues | 30.8 percentage of participants |
Secondary
Assess Safety Outcome - Safety and Tolerability
Number of participants with treatment-emergent adverse event (TEAE)
Time frame: 36 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one related Ocular TEAE in Study Eye | 8 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TEAE in Non-Study Eye | 2 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TEAE in Study Eye | 12 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one related Ocular TEAE in Non-Study Eye | 1 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TESAE in Study Eye | 1 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one non-ocular TESAE | 5 Participants |
| Anti-VEGF Control Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one TEAE | 15 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one non-ocular TESAE | 5 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one TEAE | 22 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TEAE in Study Eye | 19 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one related Ocular TEAE in Study Eye | 8 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TESAE in Study Eye | 0 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one Ocular TEAE in Non-Study Eye | 6 Participants |
| Foselutoclax Arm | Assess Safety Outcome - Safety and Tolerability | Participants with at least one related Ocular TEAE in Non-Study Eye | 0 Participants |
Secondary
Ocular Safety and Tolerability
Ocular Safety is evaluated by incidence of ocular Treatment Emergent Adverse Events (TEAEs).
Time frame: 36 weeks
Population: Subjects with at least one ocular TEAE in study eye
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | conjunctival haemorrhage | 8 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | conjunctivochalasis | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | subjects with at least one ocular TEAE in study eye | 12 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | diabetic retinopathy | 1 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | conjunctival hyperaemia | 22 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | dry eye | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | corneal abrasion | 1 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | diabetic retinal oedema | 8 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | retinal detachment | 1 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | punctate keratitis | 2 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | subretinal fluid | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | cataract aggravated | 10 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | visual acuity reduced | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | vitreous floaters | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | vitreous detachment | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | posterior capsule opacification | 0 Participants |
| Anti-VEGF Control Arm | Ocular Safety and Tolerability | hordeolum | 0 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | posterior capsule opacification | 2 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | corneal abrasion | 0 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | subjects with at least one ocular TEAE in study eye | 19 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | diabetic retinal oedema | 15 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | conjunctival haemorrhage | 15 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | conjunctival hyperaemia | 2 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | punctate keratitis | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | cataract aggravated | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | vitreous detachment | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | conjunctivochalasis | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | diabetic retinopathy | 0 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | dry eye | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | hordeolum | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | retinal detachment | 0 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | subretinal fluid | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | visual acuity reduced | 1 Participants |
| Foselutoclax Arm | Ocular Safety and Tolerability | vitreous floaters | 1 Participants |