A Phase 1, Dose-Escalating, Multi-Center, Study of iSONEP (Sonepcizumab [LT1009]) Administered as an Intravitreal Injection to Subjects With Choroidal Neovascularization Secondary to Age-Related Macular Degeneration
试验速览
- 阶段
- 1 期
- 发起方
- Lpath, Inc.
- 入组人数
- 15
- 试验地点
- 10
- 主要终点
- To determine safety, tolerability, maximum tolerated dose and dose-limiting toxicity of iSONEP following a single intravitreal injection to subjects with choroidal neovascularization secondary to AMD
研究概览
简要总结
Age-related macular degeneration (AMD) is a disease that, in time, destroys the macula, which is the central part of the retina that gives sharp central vision. The primary purpose of this study is to assess the safety of iSONEP which is a humanized monoclonal antibody against a bioactive lipid, sphingosine 1-phosphate (S1P).
详细描述
S1P modulates the AMD-associated processes of angiogenesis, inflammation and fibrosis. A potential strategy for treating choroidal neovascularization associated with AMD is to reduce the biologically available extracellular levels of S1P. iSONEP is highly selective for S1P and binds with picomolar affinity. Lpath proposes that iSONEP would deprive many cell types (fibroblasts, pericytes, vascular endothelial cells and inflammatory) of important growth and survival factors thus targeting the multiple maladaptive processes of exudative AMD that ultimately result in the loss of photoreceptors, their supporting cells, and visual acuity. Targeting simultaneously multiple components of the choroidal neovascular response is a novel approach and has the potential to be more potent than "single-targeted" therapeutics such as anti-VEGF therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •50 years and older
- •BCVA ETDRS letter score in study eye between 20-57 letters using ETDRS refraction (Snellen of 20/70-20/400)
- •Any CNV secondary to AMD in study eye, classic, minimally classic or occult with leakage on fluorescein angiography and intraretinal or subretinal fluid on OCT
- •Visual acuity in fellow eye must be 20/800 or better at 4 meters
- •Able to read, understand and sign the consent form before entering into study
排除标准
- •Ocular disease other than CNV that could compromise vision in study eye
- •Systemic immunosuppressive medication/therapy (e.g., chemotherapy, steroids)
- •Uncontrolled hypertension and/or arrhythmias
- •QT/QTc interval measurement >450 msec
- •Cancer within the last 2 years except superficial basal or squamous cell skin cancer or cervical carcinoma in situ
- •Have angioid streaks, presumed ocular histoplasmosis syndrome, myopia (>8 diopters) or CNV secondary to other causes than AMD
- •Any additional ocular diseases which have irreversibly compromised visual acuity of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema and severe non-proliferative diabetic retinopathy
- •Any intraocular or general surgery, including cataract surgery, within 2 months of Day 1
- •History of uveitis in either eye
- •Any ocular or periocular infection within 4 weeks prior to Day 1
- •Active ocular inflammation grade trace and above
- •Cup to disc ratio >0.8, IOP >21 mmHg in glaucoma subjects treated with more than 2 ocular hypotensive agents
- •Previous pars plana vitrectomy or trabeculectomy in study eye
- •History of anterior vitrectomy
- •Inability to obtain photographs, FA or OCT to document CNV, e.g. due to media opacity, allergy to fluorescein dye or lack of venous access
- •Previous intravitreal Macugen, Avastin or Lucentis (injection or drug device implantation) in study eye within 6 weeks or triamcinolone within 6 months
- •Receiving or requiring chronic concomitant therapy with systemic anti-angiogenic treatments p.o., parenteral (excluding inhaled steroids) (>5 mg) or topical corticosteroids in the study eye
- •PDT within 12 weeks prior to Day 1
- •Subjects taking systemic anticoagulants such as warfarin
- •Investigational agents or devices within 6 weeks prior to Day 1
- •Females who are pregnant or nursing and women of child bearing potential who are not using adequate contraceptive precautions
结局指标
主要结局
To determine safety, tolerability, maximum tolerated dose and dose-limiting toxicity of iSONEP following a single intravitreal injection to subjects with choroidal neovascularization secondary to AMD
时间窗: Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection
次要结局
- To characterize systemic pharmacokinetics, evaluate the immunogenicity, and investigate preliminary efficacy on retinal lesion thickness determined by OCT; size and extent of CNV and lesion area; and visual acuity(Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection)