Phase 1 Study of ALK001 for Stargardt Disease

ALK001 治疗 Stargardt 病的 1 期研究

• 批准号: 8417636
• 负责人: Leonide Saad
• 金额: $ 16.69万
• 依托单位: ALKEUS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8417636
• 关键词: Phase; Study; ALK001; Stargardt; Disease

DESCRIPTION (provided by applicant): The overall goal of this research is to develop an oral treatment for Stargardt disease, a leading cause of juvenile blindness with a prevalence of about 1 in 10,000 in the United States. Vision loss in Stargardt disease is thought to originate from excessive accumulation of vitamin A aggregates (dimers) and lipofuscin granules in the eye. ALK-001, is vitamin A specifically enriched with deuterium at a position to slow the formation of toxic vitamin A dimers in the eye. In rodent models of Stargardt disease ALK-001 resulted in a decrease in vitamin A dimers, ocular lipofuscin and in improved visual function. ALK-001 is thought to retard vitamin A dimerization and lipofuscin formation without affecting the visual cycle or normal vitamin A processing and as a consequence should not lead to visual or systemic side effects. The major hypothesis of this work is that retarding vitamin A dimerization will slow lipofuscin formation and the course of Stargardt. The goal of this grant is to perform preliminary safety evaluation and determine plasma pharmacokinetics in response to two week dosing with ALK-001 so that longer trials for efficacy can be designed and conducted. The specific aim of the grant proposal is to a complete a 2 week daily dosing, double blind, clinical trial to assess the safety and plasma-pharmacokinetics of ALK-001 in subjects with Stargardt disease.

描述(由申请人提供)： 这项研究的总体目标是开发一种治疗Stargardt病的口服疗法，Stargardt病是青少年失明的主要原因，在美国的患病率约为万分之一。Stargardt病的视力丧失被认为是由于眼睛中维生素A聚集体(二聚体)和脂褐素颗粒过度积累所致。ALK-001是一种维生素A，专门用于减缓眼睛中有毒的维生素A二聚体的形成。在Stargardt病的啮齿动物模型中，ALK-001导致维生素A二聚体、眼部脂褐素减少，并改善了视觉功能。ALK-001被认为可以延缓维生素A二聚化和脂褐素的形成，而不会影响视觉周期或正常的维生素A加工，因此不会导致视觉或全身副作用。这项工作的主要假设是，延缓维生素A二聚体将减缓脂褐素的形成和 斯塔加特的航程。这笔赠款的目标是进行初步安全性评估，并确定两周剂量ALK-001后的血浆药代动力学，以便设计和进行更长时间的疗效试验。赠款提案的具体目标是完成一项为期两周的每日剂量双盲临床试验，以评估ALK-001在Stargardt病患者中的安全性和血浆药代动力学。