Diabetic Macular Edema
Conditions
Keywords
Macular Edema, Edema, Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, Anti-Inflammatory Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Immunosuppressive Agents, Immunologic Factors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Dexamethasone, Suprachoroidal Microcatheterization, Illuminated Microcatheterization, Sustained-Release
Brief summary
The purpose of this clinical trial is to compare safety, tolerability, efficacy, and durability of two dose levels of suprachoroidal sustained-release OXU-001 (dexamethasone microspheres; DEXAspheres®) using the Oxulumis® illuminated microcatheterization device compared with intravitreal dexamethasone implant (OZURDEX®) in subjects with diabetic macular edema.
Detailed description
Fifty-two (52) week phase 2 trial with two parts. Part A is an open-label, randomized, single-dose two treatment arm comparison of two dose levels of sustained-release suprachoroidal OXU-001 (DEXAspheres® administered using the Oxulumis® illuminated microcatheterization device) in subjects with Diabetic Macular Edema. \--- Part A was only partially recruited due a non-safety related sponsor decision to stop further recruitment after 3 randomized and treated subjects. \--- Part B is a randomized, masked, active comparator, single-dose, three treatment arm comparison of two dose levels of suprachoroidal OXU-001 and IVT Ozurdex® to evaluate the safety, tolerability, efficacy, and durability in subjects with Diabetic Macular Edema (DME). \--- Part B was not initiated due a non-safety related sponsor decision in Dec 2023. \--- In Part A, after a screening period, approximately 18 adult female or male subjects will be randomized in a 1:1 ratio to receive a single administration of one of two dose levels of OXU-001 (mid-dose or high-dose). In Part B, after a screening period, approximately 110 adult female or male subjects will be randomized in a 2:2:1 ratio to receive a single administration of one of two dose levels of OXU-001 (Dose 1 or Dose 2) or Ozurdex®. From Week 12, subjects will be assessed for the need for follow-on treatment. The follow-up period after treatment administration will be up to fifty-two (52) weeks.
Interventions
DRUGOXU-001
Suprachoroidal sustained release dexamethasone acetate
DEVICESemi-automated suprachoroidal illuminated microcatheter
Ophthalmic administration device
DRUGOzurdex® Ophthalmic Intravitreal Implant
Ophthalmic dexamethasone intravitreal implant
Sponsors
Oxular Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Part A is open-label, no masking. Part B is masked for the subject and the outcomes assessing site team and central reading center.
Intervention model description
The trial was designed to include previously IVT anti-VEGF treated (in Part A and B) and treatment-naive (in Part B only) DME subjects. In Part A, approximately 18 subjects will be randomly assigned (ratio 1:1) to receive either a mid-dose or high-dose of suprachoroidal OXU-001. In Part B, approximately 110 subjects will be randomly assigned (ratio 2:2:1) to receive a single treatment of either suprachoroidal OXU-001 Dose 1, or Dose 2 or intravitreal Ozurdex® Note: Due to a non-safety related sponsor decision in Dec 2024 trial recruitment was stopped after only 3 subjects randomized and treated in Part A of the clinical trial. Part B was therefore not initiated.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 or Type 2 diabetes mellitus * Diabetic Macular edema involving the center of the fovea in the study eye * Best corrected visual acuity in the study eye between 34 and 78 (early treatment of diabetic retinopathy study) ETDRS letters
Exclusion criteria
* Macular edema is considered due to a cause other than diabetes mellitus in the study eye * Condition, in the study eye, in which visual acuity is not expected to improve from the resolution of macular edema * Macular laser photocoagulation or panretinal laser photocoagulation in the study eye performed within 16 weeks prior to screening * Active proliferative diabetic retinopathy (PDR) or sequelae of PDR in the study eye * Prior treatment with anti-VEGF in the study eye: 1. Treatment naïve group (Part B), any IVT anti-VEGF treatments in the study eye are exclusionary regardless of the time interval since injection. 2. Previously treated group (Part A and B), subjects in the previously treated group are excluded if they meet any of the below criteria for the study eye at screening: 1. Subject has received less than 3 anti-VEGF injections since treatment initiation (at least three injections must have been received for eligibility). 2. Time interval between the first anti-VEGF injection and screening is more than 40 weeks. 3. Last injection with ranibizumab or bevacizumab within 4 weeks prior to screening. 4. Last injection with aflibercept within 8 weeks prior to screening. 5. Last injection with faricimab or brolucizumab within 12 weeks prior to screening. 6. Prior treatment with SUSVIMO (Port Delivery System) implant is exclusionary. * Prior ocular treatment with steroid injections (periocular, subtenon, intravitreal) or intravitreal implants in the study eye. * Prior treatment with suprachoroidal steroids in the study eye is exclusionary. * Active malignancy or history of malignancy within the past 5 years * Uncontrolled diabetes with a hemoglobin A1c (HbA1c) more than 12% or any other uncontrolled systemic disease at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Day 0 up to Week 52 | Treatment-emergent adverse events are defined as events emerging following administration of study treatment (OXU-001 administered with the Oxulumis suprachoroidal administration device) at Visit 2 (Baseline, Day 0) |
| Frequency and Severity of Treatment-emergent Adverse Device Effects | Day 0 up to Week 52 | Treatment-emergent adverse device effects are defined as effects emerging following administration of study treatment at Visit 2 (Baseline, Day 0) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0 | Week 24 | Assessed using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. All BCVA assessments in the study eye need to be performed in duplicate. The mean of both BCVA assessments was calculated, if both ETDRS letters scores differ by more than 5 letters, the better (higher) ETDRS letter score will be used. |
| Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0 | Week 24 | Assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT) using the Central Subfield Thickness values calculated by the software of the SD-OCT devices allowed in the OXEYE clinical trial. |
| Time Interval to Subjects Requiring follow-on Treatment (From Baseline, Visit 2, Day 0) | From Week 12 through Week 52 | Timepoint for meeting pre-specified, protocol-defined criteria of disease activity recurrence. Disease activity was assessed based on Best-Corrected Visual Acuity using the Early Treatment of Diabetic Retinopathy Screening methodology and the central subfield thickness using Spectral-Domain OCT. If criteria were not met throughout Week 52, 365 days were entered. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A1: OXU-001 / Mid Dose The Oxulumis® device will be used for the administration of OXU-001 (sustained release dexamethasone acetate) via suprachoroidal microcatheterization. A single treatment with dose level 1 (mid dose) will be applied.
OXU-001: Suprachoroidal sustained release dexamethasone acetate
Semi-automated suprachoroidal illuminated microcatheter: Ophthalmic administration device | 1 |
| A2: OXU-001 / High Dose The Oxulumis® device will be used for the administration of OXU-001 (sustained release dexamethasone acetate) via suprachoroidal microcatheterization. A single treatment with dose level 2 (high dose) will be applied.
OXU-001: Suprachoroidal sustained release dexamethasone acetate
Semi-automated suprachoroidal illuminated microcatheter: Ophthalmic administration device | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | A1: OXU-001 / Mid Dose | A2: OXU-001 / High Dose | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years | 55.5 years STANDARD_DEVIATION 2.1 | 58.7 years STANDARD_DEVIATION 5.7 |
| Best-Corrected Visual Acuity (BCVA) - Study EYE | 61.0 letters read correctly on ETDRS charts | 64.0 letters read correctly on ETDRS charts STANDARD_DEVIATION 9.9 | 63.0 letters read correctly on ETDRS charts STANDARD_DEVIATION 7.2 |
| Central Subfield Thickness (Study Eye) | 417.0 µm | 502.5 µm STANDARD_DEVIATION 7.8 | 474.0 µm STANDARD_DEVIATION 49.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Puerto Rico | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
Treatment-emergent adverse events are defined as events emerging following administration of study treatment (OXU-001 administered with the Oxulumis suprachoroidal administration device) at Visit 2 (Baseline, Day 0)
Time frame: Day 0 up to Week 52
Population: Safety Analysis Set - - Number of Participants with at least 1 event
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Adverse Events of Special Interest | 0 Participants |
| A1: OXU-001 / Mid Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Ocular Treatment Emergent Adverse Events | 0 Participants |
| A1: OXU-001 / Mid Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Systemic (Non-Ocular) Treatment Emergent Adverse Events | 1 Participants |
| A1: OXU-001 / Mid Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Ocular Serious Adverse Events | 0 Participants |
| A1: OXU-001 / Mid Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Systemic (Non-Ocular) Serious Adverse Events | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Systemic (Non-Ocular) Serious Adverse Events | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Ocular Serious Adverse Events | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Ocular Treatment Emergent Adverse Events | 2 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Adverse Events of Special Interest | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Ocular and Systemic Treatment Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | Number of Participants with Systemic (Non-Ocular) Treatment Emergent Adverse Events | 2 Participants |
Primary
Frequency and Severity of Treatment-emergent Adverse Device Effects
Treatment-emergent adverse device effects are defined as effects emerging following administration of study treatment at Visit 2 (Baseline, Day 0)
Time frame: Day 0 up to Week 52
Population: Safety Analysis Set - - Number of Participants with at least 1 event
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Frequency and Severity of Treatment-emergent Adverse Device Effects | Number of Participants with Adverse Device Effects | 0 Participants |
| A1: OXU-001 / Mid Dose | Frequency and Severity of Treatment-emergent Adverse Device Effects | Number of Participants with Serious Adverse Device Effects | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Treatment-emergent Adverse Device Effects | Number of Participants with Adverse Device Effects | 0 Participants |
| A2: OXU-001 / High Dose | Frequency and Severity of Treatment-emergent Adverse Device Effects | Number of Participants with Serious Adverse Device Effects | 0 Participants |
Other Pre-specified
Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0
Assessed using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. All BCVA assessments in the study eye need to be performed in duplicate. The mean of both BCVA assessments was calculated, if both ETDRS letters scores differ by more than 5 letters, the better (higher) ETDRS letter score will be used.
Time frame: Week 24
Population: Full Analysis Set, Study Eye, Number of Participants with at least 1 post baseline assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0 | 9.0 letters read correctly on ETDRS charts | — |
| A2: OXU-001 / High Dose | Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0 | 6.5 letters read correctly on ETDRS charts | Standard Deviation 0.7 |
Other Pre-specified
Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0
Assessed using the Early Treatment of Diabetic Retinopathy (ETDRS) methodology. All BCVA assessments in the study eye need to be performed in duplicate. The mean of both BCVA assessments was calculated, if both ETDRS letters scores differ by more than 5 letters, the better (higher) ETDRS letter score will be used.
Time frame: Week 52
Population: Full Analysis Set, Study Eye
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0 | 11.0 letters read correctly on ETDRS charts | — |
| A2: OXU-001 / High Dose | Mean Change in Best-Corrected Visual Acuity (BCVA) Compared to Baseline, Visit 2, Day 0 | 10.5 letters read correctly on ETDRS charts | Standard Deviation 3.5 |
Other Pre-specified
Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0
Assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT) using the Central Subfield Thickness values calculated by the software of the SD-OCT devices allowed in the OXEYE clinical trial.
Time frame: Week 52
Population: Full Analysis Set, Study Eye
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0 | -10.0 µm | — |
| A2: OXU-001 / High Dose | Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0 | -81.5 µm | Standard Deviation 31.8 |
Other Pre-specified
Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0
Assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT) using the Central Subfield Thickness values calculated by the software of the SD-OCT devices allowed in the OXEYE clinical trial.
Time frame: Week 24
Population: Full Analysis Set, Study Eye
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0 | -16.0 µm | — |
| A2: OXU-001 / High Dose | Mean Change in Central Subfield Thickness (CST) Compared to Baseline, Visit 2, Day 0 | -165.0 µm | Standard Deviation 45.3 |
Other Pre-specified
Time Interval to Subjects Requiring follow-on Treatment (From Baseline, Visit 2, Day 0)
Timepoint for meeting pre-specified, protocol-defined criteria of disease activity recurrence. Disease activity was assessed based on Best-Corrected Visual Acuity using the Early Treatment of Diabetic Retinopathy Screening methodology and the central subfield thickness using Spectral-Domain OCT. If criteria were not met throughout Week 52, 365 days were entered.
Time frame: From Week 12 through Week 52
Population: Full Analysis Set, Study Eye
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A1: OXU-001 / Mid Dose | Time Interval to Subjects Requiring follow-on Treatment (From Baseline, Visit 2, Day 0) | 365 Days | — |
| A2: OXU-001 / High Dose | Time Interval to Subjects Requiring follow-on Treatment (From Baseline, Visit 2, Day 0) | 118.5 Days | Standard Deviation 6.4 |