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

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)

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.

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.

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.