Ranibizumab for Advanced Ocular Disease of VHL Disease

雷珠单抗治疗 VHL 疾病的晚期眼部疾病

• 批准号: 6968628
• 负责人: EMILY Y CHEW
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6968628
• 关键词: Von Hippel Lindau syndrome; cardiovascular neoplasm; eye disorder chemotherapy; gene mutation; human subject; human therapy evaluation; immunochemistry; injection /infusion; patient oriented research; vascular endothelial growth factors; visual perception

Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of an anti-VEGF therapy, ranibizumab (rhuFab V2) in 5 participants to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Participants will receive 7 intravitreal injections of study drug over a 6-month period, with the option of up to seven additional injections at the same dose and schedule during follow-up for a period of 1 year after the initiation of treatment. The primary outcome will be a change in the best-corrected visual acuity of 15 letters or more at 1 year. The secondary outcomes will be a reduction in retinal thickening and leakage at one year, and adverse events including local and systemic toxicities.

冯·希佩尔-林道综合征 (VHL) 是一种常染色体显性遗传性疾病，其中肾脏、肾上腺、胰腺、大脑、脊髓、眼睛、内耳、附睾和阔韧带中出现特定组织病理学的多种良性和恶性肿瘤和囊肿。视网膜血管瘤可能是 VHL 疾病的最早表现之一，并可能导致受影响个体的视力显着下降。这些肿瘤很少会自发消退。视力丧失的主要原因是视网膜水肿，特别是继发于周边视网膜血管瘤或视盘上或周围发现的血管瘤扩大的黄斑水肿。视网膜血管瘤的治疗取决于病变的位置和大小，但通常包括光凝疗法或冷冻疗法。然而，对于视神经上或周围的 VHL 眼部病变或周边视网膜中太大而无法对传统疗法产生反应的病变，目前还没有经过证实的有效疗法。 VHL 疾病中发现的基因突变上调血管内皮生长因子 (VEGF) 的产生。对 VHL 眼部病变以及身体其他部位发现的其他病变的免疫化学研究显示 VEGF 显着增加。这项开放标签研究将在 5 名参与者中试验使用抗 VEGF 疗法雷珠单抗 (rhuFab V2)，以研究治疗与 VHL 相关的视网膜血管瘤的潜在疗效。参与者将在 6 个月内接受 7 次玻璃体内注射研究药物，并可选择在治疗开始后 1 年内的随访期间以相同剂量和时间表进行最多 7 次注射。主要结果是 1 年内最佳矫正视力改变 15 个字母或更多。次要结果是一年后视网膜增厚和渗漏的减少，以及包括局部和全身毒性在内的不良事件。