Naloxone Lotion for the Treatment of Pruritus in Mycosis Fungoides

纳洛酮洗剂治疗蕈样肉芽肿瘙痒症

• 批准号: 9346005
• 负责人: Scott Phillips
• 金额: $ 49.96万
• 依托单位: ELORAC, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-05 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9346005
• 关键词: Naloxone; Lotion; Treatment; Pruritus; Mycosis

7. Project Summary/Abstract The project which is the subject of this grant application is a Phase 3 clinical study to demonstrate safety and efficacy of Naloxone 0.5% Hydrochloride (HCl) Lotion for the relief of pruritus associated with [the] mycosis fungoides (MF) [as well as Sèzary syndrome (SS), both being] form[s] of cutaneous t-cell lymphoma (CTCL). The seriousness of pruritus (itch) that accompanies skin disorders such as MF, the most prevalent subtype of CTCL, is often underestimated. Severe chronic pruritus has clinically significant effects on morbidity and mortality that impact clinical management of the disease its costs. As a symptom, itch is uncomfortable and annoying, distracts and disrupts activities of daily life, interferes with sleep, and may affect social interactive behavior. Moreover, chronic pruritus has been associated with considerable impairment of quality of life comparable to chronic pain.1 The mortality rate in patients with MF is estimated to be twice as frequent in patients with itching than in those without itching.2 Current medications do not completely address the pruritus associated with MF which leads to infections from excoriations. Naloxone 0.5% HCl Lotion will fill this unmet medical need. Traditional anti-pruritic drugs, i.e. antihistamines, tricyclic antidepressants, and corticosteroids, are not generally effective in managing the itch associated with MF.11 Current evidence suggests that MF related pruritus may be mediated by a peripheral opinergic pathway and provides the scientific rationale for treating MF related pruritus with the opioid antagonist. Naloxone is classified pharmacologically as an opioid antagonist with activity at multiple opioid receptors including Mu, Delta, Kappa1 and Kappa3.3 The treatment of pruritus associated with MF using a topical formulation of naloxone represents a novel therapeutic approach [as systemic administration is not practical due to the short half life of naloxone in blood.] This is a 6 – 9 week, double-blind, vehicle-controlled, crossover study of approximately 160 adult subjects that have moderate to severe pruritus (a minimum score of 5 on the 0 – 10 point scale) associated with MF [or SS]. The study is composed of a 1 week non-treatment Screening Period during which subjects will be required to complete a daily diary assessing overall pruritus. The 1 week Screening Period is followed by a two week Treatment Period, 4 – 28 day Washout Period, and another two week Treatment Period. Subjects will be randomized 1:1 to receive either Naloxone 0.5% HCl Lotion or Vehicle Lotion in the first Treatment Period, and the other in the second Treatment Period. The primary efficacy variable will be the change from Baseline in the weekly average of the 11-point Numeric Rating Scale (NRS) for Pruritus assessed at Day 14 of each Treatment Period. The planned duration of the Phase 3 study is approximately 2 years. Following this Phase 3 study, Elorac, Inc. will conduct a 6 month safety study to complete and submit a NDA to the US FDA. Six Phase 1 studies4,5,6,7,8,9 and a Phase 2 safety and efficacy trial in 15 subjects with MF or SS10 have already been completed. Naloxone Lotion for the topical treatment of pruritus associated with MF was granted orphan status by the FDA on November 23, 2010 and fast track designation on April 11, 2013.

7.项目总结/摘要 该项目是本赠款申请的主题，是一项3期临床研究，以证明安全性和 0.5%盐酸纳洛酮洗剂对真菌病相关瘙痒的疗效 蕈样肉芽肿（MF）[以及Sèzary综合征（SS），两者都是]皮肤T细胞淋巴瘤（CTCL）的形式。 伴随皮肤疾病的瘙痒（瘙痒）的严重性，如MF，MF是最普遍的亚型， CTCL往往被低估。重度慢性瘙痒症对发病率和 影响疾病临床管理的死亡率及其成本。作为一种症状，瘙痒是不舒服的， 令人烦恼，分散和扰乱日常生活活动，干扰睡眠，并可能影响社交互动 行为此外，慢性瘙痒与生活质量的显著损害有关 与慢性疼痛相当。1 MF患者的死亡率估计是慢性疼痛患者的两倍。 2目前的药物不能完全解决与瘙痒相关的 MF会导致擦伤感染。纳洛酮0.5%盐酸洗剂将填补这一未满足的医疗需求。 传统的抗癫痫药物，即抗组胺药、三环类抗抑郁药和皮质类固醇，一般不被用于治疗癫痫。 目前的证据表明，MF相关瘙痒可能是 通过外周阿片能途径介导，为治疗MF相关瘙痒提供了科学依据 阿片类拮抗剂纳洛酮被归类为阿片类拮抗剂，其活性为 多种阿片受体，包括Mu、Delta、Kappa 1和Kappa 3。 使用纳洛酮局部制剂的MF代表了一种新的治疗方法[全身给药 由于纳洛酮在血液中的半衰期短，因此不实用。 这是一项为期6 - 9周、双盲、赋形剂对照、交叉研究，约有160名成人受试者， 患有与MF [或SS]相关的中度至重度瘙痒症（0 - 10分量表上的最低评分为5分）。 本研究包括1周的非治疗筛选期，在此期间，受试者需要 完成每日日志，评估总体瘙痒。1周筛选期之后是2周 治疗期、4 - 28天洗脱期和另外两周治疗期。受试者将 在第一个治疗期以1：1的比例随机接受0.5%盐酸纳洛酮洗剂或溶剂洗剂，以及 另一个在第二个治疗期。主要有效性变量将是以下指标较基线的变化： 每次治疗第14天评估的瘙痒11点数字评定量表（NRS）每周平均值 期 III期研究的计划持续时间约为2年。在该III期研究之后，Elorac，Inc. 将进行为期6个月的安全性研究，以完成并向美国FDA提交NDA。6项I期研究4、5、6、7、8、9 在15例MF或SS 10受试者中进行的II期安全性和疗效试验已经完成。Naloxone 用于局部治疗MF相关瘙痒症的洗剂于2009年12月15日被FDA授予孤儿药地位。 2010年11月23日和2013年4月11日快速通道指定。