A Phase 1 Study of the Safety, Pharmacokinetics, and Exploratory Efficacy of Periocular Administration of AIV007 in Subjects with Macular Edema Secondary to Neovascular Age-Related Macular Degeneration (nAMD) or Diabetic Macular Edema (DME)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 19
- 试验地点
- 6
- 主要终点
- Adverse Events
研究概览
简要总结
To determine safety, pharmacokinetics, and duration of effect of periocularly administered AIV007 gel suspension in subjects with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).
详细描述
AIV007 is a multiple kinase inhibitor of vascular endothelial growth factor receptors (VEGFR 1, -2 & -3); fibroblast growth factor receptors (FGFR-1, -2, -3 & -4); and platelet-derived growth factor receptors (PDGFR-α & β)1. Lenvatinib is the active pharmaceutical ingredient in AIV007 formulation that is FDA-approved for oral administration for patients with advanced renal cell carcinoma (RCC), differentiated thyroid cancer (DTC), unresectable hepatocellular carcinoma (HCC), and advanced endometrial carcinoma (Lenvima USPI 2021; NDA 206947).
AiViva BioPharma, Inc. (AiViva) has developed a novel, thermoresponsive gel suspension of AIV007 for periocular administration to form a durable depot. This monotherapy is in development for the treatment of retinal and choroidal vascular disease (i.e., neovascular age-related macular degeneration (nAMD) & diabetic macular edema (DME)). For preclinical and clinical (AIV007-E02) studies using periocular administration, AIV007 is injected outside the eyeball and the depot forms a soft mass, referred to as posterior juxtascleral depot (PJD) placement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General inclusion Criteria:
- •Male or female subjects aged 21-90 years (inclusive) at screening
- •BCVA in the study eye at screening and baseline/Day 1: ETDRS letter score ≤ 75 and ≥ 24 (20/32 to 20/330 Snellen equivalent)
- •Subject must have received treatment within the 24 months before screening with intravitreal (IVT) injections of an anti-VEGF agent with the last anti-VEGF injection in the study eye being at least 6 weeks (42 days) before baseline/Day
- •Subject has documentation of anti-VEGF responsiveness
- •Subject must provide written informed consent before any study-related procedures are performed
- •Clear ocular media and adequate pupil dilation in both eyes to permit good-quality photographic imaging
- •nAMD subject
- •The active CNV is confirmed by FA (evidence of leakage)
- •Residual intraretinal or subretinal fluid based on SD-OCT
- •CST ≥ 300 µm as assessed by SD-OCT
- •Total lesion size < 10 disc areas (25.4 mm2)
- •Absence of geographic atrophy within 200 µm of the fovea
- •If subretinal hemorrhage is present, it must be < 50% of the total CNV lesion and/or not involve the fovea
- •If fibrosis is present, it must be <50% of the total lesion area
- •DME subject
- •Diagnosis of diabetes mellitus (Type 1 or Type 2)
- •Subject has clinically significant DME with central involvement (CST≥300 μm by OCT)
- •The decrease in vision in the study eye was determined by the investigator to be primarily the result of DME
排除标准
- •Previous treatment for nAMD or DME in the study eye other than standard-of-care anti-VEGF IVT injection, e.g., cell therapy, brachytherapy, gene therapy
- •Uncontrolled IOP, defined as an IOP > 25 mmHg
- •Poorly controlled diabetes mellitus defined as hemoglobin A1c (HbA1c) >10% at screening visit
- •The spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia (before cataract or refractive surgery) per the current prescription
- •Any history of active bacterial, viral, fungal, or parasitic ocular or periocular infection, or intraocular inflammation in either eye within the 30 days before the screening Visit
- •History of vitreous hemorrhage within 3 months before screening in the study eye
- •Uncontrolled systemic disease or any other condition or therapy that would make the participant unsuitable for the study
- •Participation in any investigational study within 60 days before the screening visit, or planned use of an investigational product or device during the study; any exposure to a prior investigational drug product must be fully washed out (at least 5 half-lives)
- •History of allergy or hypersensitivity to constituents of the study treatment formulation, topical iodine, ocular antimicrobial solutions, or clinically relevant hypersensitivity to fluorescein
研究组 & 干预措施
AIV007 low dose
Periocular injection, low dose
干预措施: AIV007 (Drug)
AIV007 intermediate dose 1
Periocular injection, intermediate dose 1
干预措施: AIV007 (Drug)
AIV007 intermediate dose 2
Periocular injection, intermediate dose 2
干预措施: AIV007 (Drug)
AIV007 intermediate dose 3
Periocular injection, intermediate dose 3
干预措施: AIV007 (Drug)
AIV007 intermediate dose 4
Periocular injection, intermediate dose 4
干预措施: AIV007 (Drug)
AIV007 High dose
Periocular injection, high dose
干预措施: AIV007 (Drug)
结局指标
主要结局
Adverse Events
时间窗: Approximately 168 days
Incidence of adverse events and serious adverse events
次要结局
- Mean change from baseline in best-corrected visual acuity (BCVA)(Approximately 168 days)
- Mean change from baseline in central subfield thickness as measured by spectral domain optical coherence tomography (SD-OCT)(Approximately 168 days)
- Mean time to rescue medication(Approximately 168 days)