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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: OXU-001; Device: Semi-automated suprachoroidal illuminated microcatheter; Drug: Ozurdex® Ophthalmic Intravitreal Implant

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 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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Friedrich Asmus, MD; Phone Number: +44 (0)1865 636200; Email: clinicaltrials@oxular.com
• Study Contact Backup: Name: Daniel Sea; Phone Number: +1 (484) 502-9814; Email: clinicaltrials@oxular.com

Study Locations

• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emmanuelli Research and Development Center, LLC
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Retinal Research Institute, LLC
  • Florida
    • Clearwater, Florida, United States, 33761
      • Blue Ocean Clinical Research West
  • Illinois
    • Oak Forest, Illinois, United States, 60452
      • University Retina and Macula Associates
  • Minnesota
    • Minneapolis, Minnesota, United States, 55337
      • Retina Consultants of Minnesota
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • Texas
    • Houston, Texas, United States, 77380
      • Retina Consultants of Texas
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute, PA
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of Texas - San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Other 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 52
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 52
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	Week 24
Mean Change in Central Subfield Thickness (CST) compared to baseline, Visit 2, Day 0	Assessed using Spectral-Domain Optical Coherence Tomography (SD-OCT)	Week 24
Time interval to subjects requiring follow-on treatment (from baseline, Visit 2, Day 0)	Timepoint for meeting pre-specified criteria of disease activity recurrence	From Week 12 through Week 52

Collaborators and Investigators

• Sponsor: Oxular Limited
• Investigators: Study Director: Friedrich Asmus, MD, Oxular Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2023
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Eye Diseases; Edema; Dexamethasone; Enzyme Inhibitors; Glucocorticoids; Physiological Effects of Drugs; Macular Edema; Immunologic Factors; Retinal Diseases; Hormones; Macular Degeneration; Immunosuppressive Agents; Anti-Inflammatory Agents; Molecular Mechanisms of Pharmacological Action; Retinal Degeneration; Hormones, Hormone Substitutes, and Hormone Antagonists; Suprachoroidal Microcatheterization; Illuminated Microcatheterization; Sustained-Release
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: OXUCT-102 - OXEYE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes