2023-503496-17-00已完成2 期
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).
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 12
- 主要终点
- Both Part A and Part B: Frequency and severity of ocular and systemic adverse events (serious, adverse events of special interest, and treatment-emergent adverse events)
研究概览
简要总结
Part A To evaluate the safety, tolerability, and feasibility of suprachoroidal OXU-001 in subjects with Diabetic Macular Edema (DME)
Part B To evaluate the safety and tolerability of suprachoroidal OXU-001 in subjects with DME.
研究设计
- 分配方式
- Randomized
- 主要目的
- Part A
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •put the subject at risk because of participation in the trial, or
- •influence the results of the trial, or
- •influence the subject’s ability to participate in the trial, or
- •may require medical or surgical intervention during study participation (e.g., cataract, vitreous hemorrhage, retinal detachment, or macular hole).
- •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
- •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: 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).
- •Last injection (intra- or periocular/subtenon) with triamcinolone acetonide within 12 weeks before screening.
- •Last injection (suprachoroidal) steroids, e.g., Xipere™, within twelve (12) weeks before screening.
- •Last injection (IVT) with dexamethasone implant (Ozurdex®) within 24 weeks before screening.
- •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.
- •Macular edema considered due to a cause other than diabetes mellitus in either eye.
- •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.
- •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.
- •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.
- •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.
结局指标
主要结局
Both Part A and Part B: Frequency and severity of ocular and systemic adverse events (serious, adverse events of special interest, and treatment-emergent adverse events)
Both Part A and Part B: Frequency and severity of ocular and systemic adverse events (serious, adverse events of special interest, and treatment-emergent adverse events)
Both Part A and Part B: Frequency and severity of device adverse effects (serious adverse device effects and treatment-emergent device adverse effects)
Both Part A and Part B: Frequency and severity of device adverse effects (serious adverse device effects and treatment-emergent device adverse effects)
次要结局
- Both Part A and Part B: Time from baseline, (Visit 2), to subjects requiring follow-on treatment (per pre-specified criteria).
- Both Part A and Part B: Mean Change BCVA (ETDRS) at Week 24 compared to baseline.
- Both Part A and Part B: Mean Change in central subfield thickness at Week 24 compared to baseline.
- Both Part A and Part B: Mean Change BCVA (ETDRS) through Week 52 compared to baseline.
- Both Part A and Part B: Mean Change in central subfield thickness through Week 52 compared to baseline.
- Part B only: Proportion of subjects requiring follow-on treatment at study visits from Week 12 through Week 52.
- Part B only: Proportion of subjects with 5-, 10-, or 15-letter (ETDRS) gain of BCVA from week 4 to week 52 compared to baseline.
- Part B only: Proportion of subjects with 5-, 10-, or 15-letter (ETDRS) loss of BCVA from week 4 to week 52 compared to baseline.
- Part B only: Proportion of subjects with BCVA >68 letters (ETDRS) at each study visit from week 4 to week 52.
- Both Part A and Part B: Mean change in NEI VFQ-25 Total Score Week 24, and Week 52 compared to baseline.
- Part A only - Assess systemic exposure of dexamethasone after administration of OXU-001.
研究者
Friedrich Asmus, MD
Scientific
Oxular IE Limited
研究点 (12)
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