Placebo Cntrld db PH.ll/lll stdy Fx-1006A trtmnt fam Amyloid Polyneuropathy

安慰剂 Cntrld db PH.ll/lll 标准 Fx-1006A trtmnt fam 淀粉样多发性神经病

• 批准号: 7599608
• 负责人: Jeffrey Neal Packman
• 金额: $ 17.85万
• 依托单位: FOLDRX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-05 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7599608
• 关键词: Placebo; Cntrld; db; PH.ll; lll

DESCRIPTION (provided by applicant): The long-term objective of the development program for Fx-1006A is to provide a treatment for FAP, a relentlessly progressive, debilitating and ultimately fatal orphan disease. The proposed study is intended to provide the primary data to support a marketing application for Fx-1006A in the treatment of FAP. Deposition of amyloid fibrils of variant transthyretin (TTR) (primarily V30M) in peripheral nerve tissue produces the condition called FAP. Mutation in TTR destabilizes the protein and causes amyloid deposition. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for FAP. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. The international Phase 2/3 study will enroll 120 early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of sensorimotor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months. The primary objectives of the study are (1) to evaluate the effect of Fx-1006A on disease progression in patients with FAP; and (2) to evaluate the safety and tolerability of chronic administration of Fx1006A in patients with FAP. The secondary study objectives are: (1) to determine the pharmacodynamic stabilization effect of Fx-1006A on human V30M TTR; and (2) to determine the population pharmacokinetics in patients with FAP. The co-primary efficacy endpoints for the study are: Response to treatment at Month 18, as indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to <2) in the Neurologic Impairment Score-Lower Limb (NIS-LL) score. Change from Baseline to 18 months in the Total Quality of Life (TQOL) score, as measured by the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN). Efficacy, safety and pharmacokinetic assessments will be conducted throughout the study.

描述（由申请人提供）： Fx-1006 A开发计划的长期目标是为FAP提供治疗，FAP是一种持续进行、使人衰弱并最终致命的孤儿病。拟定研究旨在提供主要数据，以支持Fx-1006 A治疗FAP的上市申请。 甲状腺素运载蛋白（TTR）变体（主要是V30 M）的淀粉样纤维在外周神经组织中的沉积产生了称为FAP的病症。TTR突变使蛋白质不稳定并引起淀粉样蛋白沉积。通过稳定TTR天然状态来预防淀粉样蛋白的形成应该构成FAP的有效疗法。使用TTR稳定剂药物（如Fx-1006 A）的治疗干预旨在阻止FAP患者经历的无情的神经恶化。 这项国际2/3期研究将招募120名早期至中期FAP患者，以便在感觉运动和自主神经功能障碍进展可能受到最大影响的时间点中断和稳定疾病。具有记录的V30 M TTR突变的患有FAP的男性和女性患者将接受Fx-1006 A或安慰剂，每天一次，持续十八（18）个月的时间。 本研究的主要目的是（1）评价Fx-1006 A对FAP患者疾病进展的影响;和（2）评价FAP患者长期给予Fx 1006 A的安全性和耐受性。次要研究目的是：（1）确定Fx-1006 A对人V30 M TTR的药效学稳定作用;和（2）确定FAP患者中的群体药代动力学。 本研究的协同主要疗效终点为： 第18个月时对治疗的反应，如通过神经功能缺损评分-下肢（NIS-LL）评分的改善（较基线降低）或稳定（较基线0至<2的变化）所示。 通过诺福克生活质量-糖尿病神经病变（QOL-DN）测量的总生活质量（TQOL）评分从基线至18个月的变化。 将在整个研究期间进行疗效、安全性和药代动力学评估。