An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) With Disease Progression Post-Orthotopic Liver Transplant
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Received liver transplant for treatment of hATTR amyloidosis ≥12 months before study start
- •Has increase in polyneuropathy disability (PND) score after liver transplant
- •Has received stable immunosuppressive regimen with ≤10 mg/day of prednisone for at least 3 months before study start
- •Has Karnofsky Performance Status (KPS) of ≥70%
- •Has vitamin A level greater than or equal to lower limit of normal
排除标准
- •Has previously received inotersen or patisiran
- •Has clinically significant liver function test abnormalities
- •Has known portal hypertension with ascites
- •Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m^2
- •Has known leptomeningeal amyloidosis
- •Has infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
- •Has New York Heart Association heart failure classification of >2
- •Is wheelchair bound or bedridden
- •Has received organ transplants other than liver transplant
- •Will be using another tetramer stabilizer during the study
研究组 & 干预措施
Patisiran
Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.
干预措施: Patisiran (Drug)
结局指标
主要结局
Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
时间窗: Baseline, Months 6 and 12
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.
次要结局
- Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12(Baseline, Month 12)
- Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12(Baseline, Month 12)
- Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12(Baseline, Month 12)
- Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12(Baseline, Month 12)
- Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12(Baseline, Month 12)
- Percentage of Participants With Adverse Events(From baseline to end of study at Month 13)