A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects With Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
研究概览
简要总结
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
详细描述
** See updated study design under ClinicalTrials.gov Identifier NCT04882735. **
Transthyretin amyloid polyneuropathy (ATTR-PN), also called "Familial Transthyretin-Mediated Amyloid Polyneuropathy (FAP)" is a hereditary condition caused by mutations in the TTR gene. It is estimated that around 10,000 people in the world are affected.
In ATTR-PN, amyloid builds up in the nerves that detect temperature, pain, and touch. Patients with ATTR-PN can experience a loss of sensation, tingling, numbness, or pain in the hands and feet (also called peripheral neuropathy).
In this study Eidos is researching the investigational drug AG10 800mg (2 tablets) administered orally twice a day. Through the study, Eidos wants to evaluate the efficacy and safety of AG10 in patients with ATTR-PN versus placebo.
This is an 18 month, placebo-controlled study. This means that, during the 18 month study, investigators conducting the research and study participants will not know whether the study participant is receiving AG10 or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be male or female ≥18 to ≤90 years of age;
- •Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam findings and/or neurophysiological test findings consistent with the diagnosis of ATTR-PN;
- •Have an NIS of 5 to 130 (inclusive) during screening;
- •Have a nerve conduction studies (NCS) score [sum of the sural sensory nerve action potential (SNAP), tibial compound muscle action potential (CMAP), ulnar SNAP, ulnar CMAP, and peroneal CMAP] of ≥2 points during screening. NCS is a component of mNIS+7;
- •Have a mutation consistent with ATTR-PN either documented in medical history or confirmed by genotyping obtained at Screening prior to randomization. *No genetic testing is needed for subjects who are recipients of domino liver transplants;
- •Have an anticipated survival of ≥2 years
- •Have Karnofsky performance status ≥60 %;
排除标准
- •Had a prior liver transplantation or is planning to undergo liver transplantation with a wild-type organ graft as treatment for symptomatic ATTR-PN during the study period.
- •Note: Recipients of a "domino" liver transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their graft are allowed under this protocol, as long as re-transplantation to treat ATTR-PN is not planned during the study period and meets all other eligibility criteria;
- •Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
- •Has Vitamin B-12 levels below the lower limit of normal (LLN);
- •Has clinical evidence of untreated hyper/hypothyroidism;
- •Has leptomeningeal TTR amyloidosis;
- •Has Type 1 diabetes;
- •Has had Type 2 diabetes for ≥5 years;
- •Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;
- •Has NYHA heart failure classification >Class II
- •Had a malignancy within 2 years, except for basal or squamous cell carcinoma of
- •Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or other gene silencing agents, marketed drug products lacking a label indication for ATTR- PN (e.g., diflunisal, doxycycline), natural products or derivatives used as unproven therapies for ATTR-PN (e.g., green tea extract, tauroursodeoxycholic acid [TUDCA]/ursodiol), within 14 days, or 90 days for patisiran and 180 days for inotersen prior to dosing. Prior to screening, tafamidis, if already prescribed to potential subjects as part of their established background therapy, is allowed at the labeled dosage and administration of 20 mg/day for the treatment of ATTR-PN with, i in the opinion of the Investigator, evidence of disease progression while on tafamidis treatment
研究组 & 干预措施
AG10 800 mg
TTR stabilizer administered orally twice daily (BID)
干预措施: AG10 (Drug)
Placebo
Placebo administered orally twice daily (BID)
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
时间窗: 18 Months
Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.
次要结局
未报告次要终点