Suprachoroidal Sustained-Release OXU-001 Compared to Intravitreal Ozurdex® in the Treatment of Diabetic Macular Edema

Study Overview
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Brief Summary
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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
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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 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). 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.

Official Title
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A Multi-Center, Randomized, Parallel-Group, Phase 2, Masked, Three-Arm Trial 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 (OXEYE)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: OXU-001
* Device: Semi-automated suprachoroidal illuminated microcatheter
* Drug: Ozurdex® Ophthalmic Intravitreal Implant


Participation Criteria
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Eligibility Criteria
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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: Treatment naïve group (Part B), any IVT anti-VEGF treatments in the study eye are exclusionary regardless of the time interval since injection. 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: Subject has received less than 3 anti-VEGF injections since treatment initiation (at least three injections must have been received for eligibility). Time interval between the first anti-VEGF injection and screening is more than 40 weeks. Last injection with ranibizumab or bevacizumab within 4 weeks prior to screening. Last injection with aflibercept within 8 weeks prior to screening. Last injection with faricimab or brolucizumab within 12 weeks prior to screening. 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.

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
Interventional Model Description: The trial will 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®
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: OXU-001 / Mid dose<br>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. | Drug: OXU-001<br>* Suprachoroidal sustained release dexamethasone acetate<br>* Other names: DEXAspheres®;Device: Semi-automated suprachoroidal illuminated microcatheter<br>* Ophthalmic administration device<br>* Other names: Oxulumis®;|
| Experimental: A2: OXU-001 / High Dose<br>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. | Drug: OXU-001<br>* Suprachoroidal sustained release dexamethasone acetate<br>* Other names: DEXAspheres®;Device: Semi-automated suprachoroidal illuminated microcatheter<br>* Ophthalmic administration device<br>* Other names: Oxulumis®;|
| Experimental: B1: OXU-001 / Mid Dose<br>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. | Drug: OXU-001<br>* Suprachoroidal sustained release dexamethasone acetate<br>* Other names: DEXAspheres®;Device: Semi-automated suprachoroidal illuminated microcatheter<br>* Ophthalmic administration device<br>* Other names: Oxulumis®;|
| Experimental: B2: OXU-001 / High Dose<br>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. This dose may be adpated based on the outcome of a Week 6 data review of Part A | Drug: OXU-001<br>* Suprachoroidal sustained release dexamethasone acetate<br>* Other names: DEXAspheres®;Device: Semi-automated suprachoroidal illuminated microcatheter<br>* Ophthalmic administration device<br>* Other names: Oxulumis®;|
| Active Comparator: B3: Ozurdex®<br>A single treatment with intravitreal Ozurdex® | Drug: Ozurdex® Ophthalmic Intravitreal Implant<br>* Ophthalmic dexamethasone intravitreal implant<br>* Other names: intravitreal dexamethasone implant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 at Visit 2 (Baseline, Day 0) | Week 24 | 
| Frequency and severity of treatment-emergent device adverse effects | Treatment-emergent device adverse effects are defined as effecs emerging following administration of study treatment at Visit 2 (Baseline, Day 0) | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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