Diabetic Macular Edema (DME)
Conditions
Keywords
Retinal disease, Macular edema, Diabetes mellitus, Diabetic macular edema
Brief summary
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
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.
Interventions
DRUGUBX1325
Patients will be administered a single 50 μL UBX1325 IVT injection
OTHERSham
Sham procedure
Sponsors
Unity Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study will be double masked, so patients and Investigators are masked to the treatment assigned, while certain roles at the site and at the Sponsor are unmasked. Sites will have a qualified injector who is unmasked to perform the study treatment injection or sham procedure, as well as certain post-injection assessments on Day 1 only.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | 48 weeks | The systemic safety and tolerability is evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by System organ class Preferred Term. |
| Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Up to Week 12, 24 and 48 weeks | Ocular Safety is evaluated by incidence of Treatment Emergent Adverse Events (TEAEs). Ocular TEAEs consisted of progression of disease or were related to the IVT injection component of the UBX1325 drug administration process |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 12, 24 and 48 | Best Corrected Visual Acuity was assessed using the ETDRS chart starting at 4 meters |
Countries
Canada, United States
Participant flow
Pre-assignment details
each participant contributed only one study eye
Participants by arm
| Arm | Count |
|---|---|
| Sham Control Sham: Sham procedure | 33 |
| UBX1325 UBX1325: Patients will be administered a single 10 μg UBX1325 IVT injection | 32 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Completed 24 weeks before study extension to 48 weeks was available as per Protocol version 4.0 | 4 | 5 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Site Closure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sham Control | UBX1325 | Total |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 9.09 | 63.6 years STANDARD_DEVIATION 9.33 | 62.5 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 24 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Eye Color Blue | 8 Participants | 10 Participants | 18 Participants |
| Eye Color Brown | 18 Participants | 19 Participants | 37 Participants |
| Eye Color Green | 0 Participants | 2 Participants | 2 Participants |
| Eye Color Hazel | 7 Participants | 0 Participants | 7 Participants |
| Eye Color Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 24 Participants | 49 Participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Male | 20 Participants | 24 Participants | 44 Participants |
| Study Eye Left Eye | 11 Participants | 18 Participants | 29 Participants |
| Study Eye Right eye | 22 Participants | 14 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 32 |
| other Total, other adverse events | 31 / 33 | 24 / 32 |
| serious Total, serious adverse events | 4 / 33 | 5 / 32 |
Outcome results
Primary
Ocular Safety and Tolerability of a Single IVT Injection of UBX1325
Ocular Safety is evaluated by incidence of Treatment Emergent Adverse Events (TEAEs). Ocular TEAEs consisted of progression of disease or were related to the IVT injection component of the UBX1325 drug administration process
Time frame: Up to Week 12, 24 and 48 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal exudates | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Meibomian gland dysfunction | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye irritation | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival haemorrhage | 2 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Foreign body sensation in eyes | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract nuclear | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous floaters | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Dry eye | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Visual acuity reduced | 2 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Punctate keratitis | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival hyperaemia | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Anterior chamber pigmentation | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous haemorrhage | 5 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal haemorrhage | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Posterior capsule opacification | 1 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Macular thickening | 2 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Diabetic retinal oedema | 18 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Subjects with At Least One Ocular TEAE in Study Eye | 28 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal oedema | 2 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye disorders | 28 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Ocular hypertension | 0 Participants |
| Sham Control | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract subcapsular | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Ocular hypertension | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Subjects with At Least One Ocular TEAE in Study Eye | 23 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye disorders | 23 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Diabetic retinal oedema | 14 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival haemorrhage | 8 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous haemorrhage | 2 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Macular thickening | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal oedema | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract subcapsular | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye irritation | 2 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract nuclear | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Visual acuity reduced | 0 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Anterior chamber pigmentation | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival hyperaemia | 0 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Dry eye | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Foreign body sensation in eyes | 0 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Meibomian gland dysfunction | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Posterior capsule opacification | 0 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Punctate keratitis | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal exudates | 0 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal haemorrhage | 1 Participants |
| UBX1325 | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous floaters | 0 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Foreign body sensation in eyes | 0 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract subcapsular | 2 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye disorders | 51 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Meibomian gland dysfunction | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal oedema | 3 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Macular thickening | 3 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Ocular hypertension | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous haemorrhage | 7 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Vitreous floaters | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Posterior capsule opacification | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival haemorrhage | 10 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal haemorrhage | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Punctate keratitis | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Anterior chamber pigmentation | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Visual acuity reduced | 2 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Diabetic retinal oedema | 32 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Conjunctival hyperaemia | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Cataract nuclear | 2 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Subjects with At Least One Ocular TEAE in Study Eye | 51 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Dry eye | 1 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Eye irritation | 2 Participants |
| Overall | Ocular Safety and Tolerability of a Single IVT Injection of UBX1325 | Retinal exudates | 1 Participants |
Primary
Systemic Safety and Tolerability of a Single IVT Injection of UBX1325.
The systemic safety and tolerability is evaluated by incidence of Treatment Emergent Adverse Events (TEAEs) by System organ class Preferred Term.
Time frame: 48 weeks
Population: The Safety Analysis Set includes all patients who received a single IVT treatment of UBX1325 or sham. Summary statistics are frequency (percentage of column total).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Blood and lymphatic system disorders - Anemia | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders-Visual acuity reduced | 1 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Coronary artery occlusion | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Nervous system disorders - Cerebrovascular accident | 1 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders - Vitreous haemorrhage | 1 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Subjects with at Least One Serious TEAE | 4 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Vascular disorders - Aortic stenosis | 1 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Cellulitis | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication- Skin abrasion | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Atrial fibrillation | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Pneumonia | 0 Participants |
| Sham Control | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication - Ankle fracture | 0 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Pneumonia | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication - Ankle fracture | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication- Skin abrasion | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Coronary artery occlusion | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Vascular disorders - Aortic stenosis | 0 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Nervous system disorders - Cerebrovascular accident | 0 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders-Visual acuity reduced | 0 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Blood and lymphatic system disorders - Anemia | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders - Vitreous haemorrhage | 0 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Subjects with at Least One Serious TEAE | 5 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Cellulitis | 1 Participants |
| UBX1325 | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Atrial fibrillation | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Vascular disorders - Aortic stenosis | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Subjects with at Least One Serious TEAE | 9 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Blood and lymphatic system disorders - Anemia | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Atrial fibrillation | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Cardiac disorders - Coronary artery occlusion | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders-Visual acuity reduced | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Eye disorders - Vitreous haemorrhage | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Cellulitis | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Infections and infestations - Pneumonia | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication - Ankle fracture | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Injury, poisoning and procedural complication- Skin abrasion | 1 Participants |
| Overall | Systemic Safety and Tolerability of a Single IVT Injection of UBX1325. | Nervous system disorders - Cerebrovascular accident | 1 Participants |
Secondary
Changes in Best Corrected Visual Acuity (BCVA) From Baseline
Best Corrected Visual Acuity was assessed using the ETDRS chart starting at 4 meters
Time frame: Week 12, 24 and 48
Population: MMRM Model for BCVA Change from Baseline (Hypothetical Strategy) Full Analysis Set. The hypothetical strategy included all subjects but excluded observations post-rescue.~The Full Analysis Set includes all randomized subjects who received a single IVT treatment of UBX1325 or sham, have a baseline BCVA assessment, and at least one post-baseline BCVA assessment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Sham Control | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 48 | 0.6 ETDRS Letters | Standard Error 2.9 |
| Sham Control | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 12 | 1.5 ETDRS Letters | Standard Error 1.68 |
| Sham Control | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 24 | -1.4 ETDRS Letters | Standard Error 1.99 |
| UBX1325 | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 12 | 4.7 ETDRS Letters | Standard Error 1.59 |
| UBX1325 | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 24 | 6.7 ETDRS Letters | Standard Error 1.88 |
| UBX1325 | Changes in Best Corrected Visual Acuity (BCVA) From Baseline | Week 48 | 6.2 ETDRS Letters | Standard Error 2.12 |