Evaluation of Suprachoroidal Dexamethasone Acetate (OXU-001) Versus Intravitreal Dexamethasone Implant in Diabetic Macular Edema
- Trial ID
- 2023-503496-17-00
- Protocol
- OXUCT-102
- Sponsor
- Oxular IE Limited
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety**, tolerability, and feasibility of suprachoroidal OXU-001 in subjects with **Diabetic Macular Edema (DME)**. This is crucial as it determines the potential of OXU-001 as a viable treatment option for DME, ensuring that it can be administered safely and effectively to patients.
Secondary objectives include:
- Evaluating the durability of suprachoroidal OXU-001 in subjects with DME, which is important for understanding the long-term effects and potential benefits of the treatment.
- Exploring the efficacy of suprachoroidal OXU-001 by assessing changes in visual acuity, edema control, and the impact on vision-related quality of life in subjects with DME. This helps in determining the therapeutic effectiveness of the treatment.
- Assessing systemic exposure of **dexamethasone** after administration of OXU-001 in Part A, which is essential for understanding the pharmacokinetics and systemic safety profile of the drug.
Participants
The clinical trial involves a total of **84 participants** diagnosed with **Diabetic Macular Edema (DME)**. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with either Type 1 or Type 2 diabetes mellitus. Participants are required to have DME involving the center of the fovea with a central subfield thickness of at least 320 µm, as confirmed by spectral domain optical coherence tomography (SD OCT). The trial population was selected based on their ability to understand and sign an informed consent form, and their willingness to comply with contraceptive measures if applicable. The participants are generally in a stable health condition, with specific visual acuity requirements for the study eye. Lifestyle considerations such as diet and physical activity are not explicitly mentioned, but participants must agree not to engage in any other clinical trials during the study period. The trial does not include vulnerable populations, ensuring a focus on the safety and tolerability of the investigational treatment in a well-defined cohort.
Plans and Procedures
The clinical trial is a multi-center, randomized, parallel-group, Phase 2, masked, three-arm study designed to evaluate the **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 (DME)**. The trial is structured to include both Part A and Part B, with the primary objective of assessing the frequency and severity of ocular and systemic adverse events, as well as device-related adverse effects. Secondary endpoints include the time to follow-on treatment, changes in best-corrected visual acuity (BCVA), and central subfield thickness over a 52-week period.
The trial is expected to last until March 31, 2025, with recruitment starting on August 1, 2023. Participants will be involved in the study for approximately 52 weeks. The trial design includes an initial screening visit to confirm eligibility based on criteria such as age, diagnosis of diabetes mellitus, and specific ocular measurements. Following the screening, eligible participants will be randomized into one of the three study arms. The study involves multiple visits, including baseline, treatment, and follow-up visits at specified intervals to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, assessing the final outcomes and any long-term effects of the treatment.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or choose to withdraw consent. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent and are aware of the potential risks and benefits associated with the study. The use of the Oxulumis® device is integral to the administration of OXU-001, with visual confirmation of correct deployment being a critical step in the procedure. The trial aims to provide valuable insights into the treatment of DME, potentially offering new therapeutic options for patients with this condition.
Treatment
The clinical trial involves the administration of **OXU-001**, a **suspension for injection** containing **dexamethasone acetate Ph. Eur.** as the active substance. This experimental medication is delivered using the Oxulumis® Illuminated Microcatheterization Device, which is a sterile, manually operated, minimally invasive, single-use device. The device is designed to deploy a therapeutic drug delivery-guiding illuminated ophthalmic microcatheter into the suprachoroidal space. The illumination feature ensures correct deployment of the microcatheter before the administration of OXU-001. The drug is administered through the microcatheter using a syringe attached to the device. The maximum daily dose of OXU-001 is 1.5 mg, with a total dose not exceeding 1.5 mg over a treatment period of one day. The route of administration is suprachoroidal.
Another experimental treatment in the trial is a higher dose of **OXU-001**, also a **suspension for injection** with the same active substance, **dexamethasone acetate Ph. Eur.** This formulation is similarly administered using the Oxulumis® device. The maximum daily dose for this higher dose level is 3 mg, with a total dose not exceeding 3 mg over a treatment period of one day. The administration route remains suprachoroidal.
The comparator treatment in the study is **OZURDEX 700 micrograms intravitreal implant in applicator**, which contains **dexamethasone** as the active substance. This non-experimental treatment is delivered via an intravitreal implant using an applicator. The maximum daily dose is 0.7 mg, with a total dose not exceeding 0.7 mg over a treatment period of one day. The route of administration for OZURDEX is intravitreal use. The device used for administration, the Ozurdex applicator, is CE marked, ensuring compliance with European safety standards.
Efficacy
The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints focus on the frequency and severity of ocular and systemic adverse events, as well as device-related adverse effects. These include serious adverse events, adverse events of special interest, and treatment-emergent adverse events. The secondary endpoints will evaluate the time from baseline to when subjects require follow-on treatment, mean change in Best Corrected Visual Acuity (BCVA) using the ETDRS scale at Week 24 and through Week 52, and mean change in central subfield thickness at the same time points. Additionally, the proportion of subjects with specific gains or losses in BCVA, as well as those achieving a BCVA greater than 68 letters, will be assessed from Week 4 to Week 52. The mean change in the NEI VFQ-25 Total Score at Week 24 and Week 52 compared to baseline will also be measured. For Part A, systemic exposure of **dexamethasone** after administration of OXU-001 will be assessed.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Able to understand and sign an informed consent form.
- At least eighteen (18) years of age at the time of screening.
- Have been diagnosed with Type 1 or Type 2 diabetes mellitus.
- Have DME involving the center of the fovea with central subfield thickness (CST) in the study eye at the screening visit, confirmed by the CRC, of at least 320 µm on SD OCT (measurement from the Retinal Pigment Epithelium, RPE, to the Inner Limiting Membrane, ILM, inclusively).
- Have BCVA in the study eye between 34 and 78 letters ETDRS (approximate Snellen acuity of 20/200-20/32) at the screening visit. For eligibility assessments, only the ETDRS BCVA letter score is considered relevant.
- For women who are not postmenopausal (i.e., at least 12 months of non-therapy-induced amenorrhea or surgically sterile (absence of ovaries and/or uterus)) agreement to remain abstinent or use combined contraceptive methods that result in a failure rate of less than 1% per year from the treatment visit (Visit 2, Day 0) until the end of trial participation, or, if subjects discontinue trial participation prior to Week 52 completion, for at least 52 weeks from the treatment visit (Visit 2, Day 0). Examples of contraceptive methods with an expected failure rate of less than 1% per year include male sterilization, hormonal implants, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of less than 1% per year. Barrier methods must always be supplemented with the use of a spermicide.
- Males must agree to use a barrier method of contraception starting from the treatment visit (Visit 2, Day 0) until the end of trial participation, or, if subjects discontinue trial participation prior to Week 52 completion, for at least 52 weeks from the treatment visit (Visit 2, Day 0).
- Subject must be willing not to participate in any other clinical trial including an investigational medicinal product (IMP) or an investigational device until the end of trial participation.
Exclusion Criteria
- Presence of any significant ocular or non-ocular disease/disorder (or medication and/or laboratory test abnormalities) which, in the opinion of the Investigator and with the concurrence of the Oxular Medical Monitor, may 1. put the subject at risk because of participation in the trial, or 2. influence the results of the trial, or 3. influence the subject’s ability to participate in the trial, or 4. may require medical or surgical intervention during study participation (e.g., cataract, vitreous hemorrhage, retinal detachment, or macular hole).
- Macular edema considered due to a cause other than diabetes mellitus in either eye.
- Condition, in the study eye, in which visual acuity is not expected to improve from the resolution of macular edema (e.g., foveal atrophy, clinically relevant loss of ellipsoid zone, pigment abnormalities, vitreomacular traction, or nonretinal causes) as determined by the investigator supported by a review by the CRC.
- Conditions, in the study eye, that may render the administration of study treatment, intravitreal implant insertion, or suprachoroidal microcatheter insertion and deployment difficult or subject the patient to excessive risk of complications. Examples include but are not limited to ocular surface disease with significant conjunctival edema and/or inflammation, ocular hypotony, scleral staphylomas, necrotizing scleritis, scleral melting, excessive choroidal scarring e.g., associated with pan-retinal photocoagulation, amongst others.
- Macular laser photocoagulation or panretinal laser photocoagulation (PRP) in the study eye performed within sixteen (16) weeks prior to screening.
- Active proliferative diabetic retinopathy (PDR) or sequelae of PDR (including iris neovascularization, vitreous hemorrhage, tractional retinal detachment, extensive scarring following PRP) at screening in the study eye.
- History of recurrent or active intraocular inflammation in either eye (e.g., uveitis) within twelve (12) weeks prior to screening.
- Infectious eye disease like infectious blepharitis, keratitis, or conjunctivitis in either eye within four (4) weeks of screening.
- IOP ≥ 22 mmHg, or glaucomatous disc changes (i.e., a cup disc ratio greater than 0.8) in the study eye at screening. History of glaucoma surgery, and or current anti-glaucoma therapy with more than two active substances (in separate or a combination preparation) are exclusionary.
- History of closed-angle glaucoma.
- IOP <6mmHg (hypotony) in the study eye at screening.
- Spherical equivalent of the refractive error of −6 diopters of myopia or worse (prior to cataract or refractive surgery) at screening.
- Cataract or other media opacity that limits the ability to obtain the planned imaging assessments.
- History of retinal detachment.
- Prior treatment with IVT 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: a) Subject has received less than three (3) anti-VEGF injections since treatment initiation (at least three injections must have been received for eligibility). b) Time interval between the first anti-VEGF injection and screening is more than forty (>40) weeks. c) Last injection with ranibizumab or bevacizumab within four (4) weeks prior to screening. d) Last injection with aflibercept within eight (8) weeks prior to screening. e) Last injection with faricimab or brolucizumab within twelve (12) weeks prior to screening. f) 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 (Part A and B). A history of topical ocular steroids is not exclusionary.
- Prior ocular treatment with steroid injections (periocular, subtenon, intravitreal) or intravitreal implants in the fellow eye (Part A) (due to potential interference with PK measurements). 1. Last injection (intra- or periocular/subtenon) with triamcinolone acetonide within 12 weeks before screening. 2. Last injection (suprachoroidal) steroids, e.g., Xipere™, within twelve (12) weeks before screening. 3. Last injection (IVT) with dexamethasone implant (Ozurdex®) within 24 weeks before screening. 4. Prior treatment with longer duration implants (e.g., fluocinolone acetonide IVT implant, Iluvien) is exclusionary.
- Prior treatment with suprachoroidal steroids in the study eye is exclusionary.
- Concurrent use of systemic glucocorticoid medications or systemic steroids within twelve (12) weeks before screening is exclusionary. Intranasal, inhaled, and extra-ocular topical corticosteroids are allowed.
- Prior IVT or suprachoroidal treatment with investigational agents in either eye (e.g., agents with anti-VEGF activity, or combined pharmacologic activity, gene therapies, cell therapies, or any other therapeutic modality) at any time.
- Participation in a clinical trial in which an investigational drug (with other routes of administration than IVT or suprachoroidal) was administered within 90 days of screening or 5 half-lives of the investigational drug, whichever is longer.
- Treatment with ocriplasmin (Jetrea®) at any time.
- History of vitreoretinal surgery (including surgery for retinal detachment or scleral buckle) in the study eye. Vitrectomy is only exclusionary, if within 12 weeks prior to screening.
- Any other previous ophthalmic surgeries, uncomplicated cataract surgery, or uncomplicated trauma in the study eye within twelve (12) weeks prior to screening. Complicated cataract surgery or trauma that may impact access and/or drug delivery to the suprachoroidal space are exclusionary.
- Part B only: Any history of surgical complications in the study eye that may increase the risk of anterior chamber migration of intravitreal implants (e.g., torn or ruptured posterior lens capsule, implantation of any iris-fixated or sclera-fixated intraocular lenses, iridectomy) regardless of the time interval between the procedure and the study enrollment.
- Hypersensitivity to OXU-001, or any of the excipients in the OXU-001 formulation or Oxulumis® device components.
- Hypersensitivity to components of Ozurdex® for subjects in Part B only.
- Active malignancy or history of malignancy within the past five (5) years.
- Uncontrolled diabetes with a hemoglobin A1c (HbA1c) > 12% or any other uncontrolled systemic disease at screening.
- Uncontrolled hypertension, defined as blood pressure with a systolic value of ≥ 160mmHg or a diastolic value of ≥ 100 mmHg upon repeat assessment at screening.
- History of myocardial infarction, stroke, transient ischemic attack, acute congestive heart failure, or any acute coronary event within 90 days before screening.
- Subjects who are pregnant or breastfeeding at the screening visit, or who test positive for pregnancy at the screening visit or are unwilling to use adequate birth control methods to prevent pregnancy throughout the study.
- Subjects who were previously randomized in this trial, but in whom administration of study treatment could not be completed.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Hungary | Not Recruiting | 01 Aug 2023 | 20 |
 Spain | Not Recruiting | 01 Aug 2023 | 24 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OXU-001 | Test | SUSPENSION FOR INJECTION | SUPRACHOROIDAL | 1.5 | 1 | PRD10263743 |
OZURDEX 700 micrograms intravitreal implant in applicator | Comparator | INTRAVITREAL IMPLANT IN APPLICATOR | INTRAVITREAL USE | 0.7 | 1 | PRD9771148 |
OXU-001 | Test | SUSPENSION FOR INJECTION | SUPRACHOROIDAL | 3 | 1 | PRD10263744 |