NCT03767829终止1 期
A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending and Multiple-dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-AAT02 in Healthy Adult Subjects and Patients With ZZ Type Alpha-1 Antitrypsin Deficiency Liver Disease
Alnylam Pharmaceuticals1 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2018年12月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of single or multiple doses of ALN-AAT02. The study will be conducted in 2 sequential phases in which Part A will be a single-ascending dose (SAD) phase in healthy participants, and Part B will be a multiple-ascending dose (MAD) phase in participants with ZZ type alpha-1 antitrypsin deficiency (PiZZ) and biopsy-proven alpha-1 antitrypsin (AAT) deficiency-associated liver disease.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female, aged 18 to 65 years, inclusive;
- •Has normal 12-lead electrocardiogram (ECG);
- •Has body mass index (BMI) between 18 and 30 kg/m^2, inclusive;
- •Has been a nonsmoker for at least 5 years before screening;
- •Part A only: Has Alpha-1 antitrypsin (AAT) levels within normal limits;
- •Part A only: Has adequate Forced Expiratory Volume in 1 second (FEV1) and adequate FEV1/forced vital capacity ratio;
- •Part B only: Has documented ZZ type AAT by genotype;
- •Part B only: Has liver biopsy within 90 days of the first dose of study drug demonstrating ZZ type alpha-1 antitrypsin deficiency (PiZZ AATD) liver disease;
- •Part B only: Has adequate post-bronchodilator FEV1 and adequate diffusing capacity of the lung for carbon monoxide;
- •Part B only: If on any maintenance medication, is likely to be able to remain on a stable medication regimen for the duration of the study (no new medications within 30 days prior to first dose of study drug).
排除标准
- •Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
- •Has clinically significant abnormal laboratory results;
- •Received an experimental drug within 30 days of dosing;
- •Has a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc);
- •Part A only: Has estimated glomerular filtration equal to or below 60 mL/min/1.73 m^2 at screening;
- •Part A only: Has a history of asthma or recurrent or chronic lung disease, excluding resolved childhood asthma;
- •Part A only: Has a history of chronic liver disease;
- •Part B only: Has estimated glomerular filtration equal to or below 45 mL/min/1.73 m^2 at screening;
- •Part B only: Received an augmentation therapy for AAT deficiency within 8 weeks of first dose of study drug;
- •Part B only: Has a history of chronic liver disease from any known cause other than ZZ type AAT deficiency;
- •Part B only: Has a history of hepatic encephalopathy;
- •Part B only: Has a history of gastrointestinal bleeding or ascites.
研究组 & 干预措施
Part B: MAD: Placebo
Placebo Comparator
Participants will be administered multiple doses of matching placebo.
干预措施: Placebo (Drug)
Part A: SAD: ALN-AAT02
Experimental
Participants will be administered a single dose of ALN-AAT02.
干预措施: ALN-AAT02 (Drug)
Part A: SAD: Placebo
Placebo Comparator
Participants will be administered a single dose of matching placebo.
干预措施: Placebo (Drug)
Part B: MAD: ALN-AAT02
Experimental
Participants will be administered multiple doses of ALN-AAT02.
干预措施: ALN-AAT02 (Drug)
结局指标
主要结局
Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)
时间窗: Part A: up to approximately 12 months; Part B: up to approximately 18 months
次要结局
- Change From Baseline in Serum Levels of Alpha-1 Antitrypsin (AAT)(Part A: baseline up to Day 85 and every 84 days up to approximately 12 months; Part B: baseline up to Day 169 and every 84 days up to approximately 18 months)
- Maximum Observed Plasma Concentration (Cmax) for ALN-AAT02(Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87)
- Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ALN-AAT02(Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87)
- Apparent Terminal Elimination Half-life (t1/2) for ALN-AAT02(Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87)
- Fraction Eliminated in Urine (fe) of ALN-AAT02(Part A: Day 1; Part B: Days 1 and 85)
- Time to Reach Cmax (tmax) for ALN-AAT02(Part A: Days 1, 2, 3, 8 and 15; Part B: Days 1, 2, 3, 29, 85, 86 and 87)
- Amount of Full Length Drug Excreted in Urine (Ae) of ALN-AAT02(Part A: Day 1; Part B: Days 1 and 85)
研究者
研究点 (1)
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