NCT02227459已完成1 期
A Phase 1b/2, Open Label, Randomized, Repeat Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Biological Activity, and Pharmacokinetics of ND-L02-s0201 Injection, A Vitamin A-coupled Lipid Nanoparticle Containing siRNA Against HSP47, in Subjects With Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)
Bristol-Myers Squibb2 个研究点 分布在 2 个国家目标入组 25 人开始时间: 2014年10月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Number of participants with serious and non-serious adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of multiple doses of ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female between 18 and 75 years
- •Diagnosis of METAVIR F3-4 hepatic fibrosis determined by liver biopsy done within 12 months before screening (Cohort 1) or at the pre-dose biopsy within 6 weeks before treatment (Cohorts 2 and 3)
- •Adequate and stable synthetic hepatic function (albumin ≥ 3 g/dL, international normalized ratio [INR] ≤ 1.4 x upper limit of normal [ULN] and stable by prior medical history).
- •Adequate and stable hepatic function as measured by alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamate transferase (GGTP), and total bilirubin (ALT/AST ≤ 5 x ULN, ALP ≤ 4 x ULN, GGTP ≤ 4 x ULN, bilirubin ≤ 2x ULN and stable by prior medical history).
- •Platelet count ≥ 75,000/mm3, hemoglobin ≥ 10 g/dL, and white blood cell count (WBC) > 3000/µL.
- •No signs of decompensated liver disease (ascites, hepatic encephalopathy, or variceal bleeding).
- •No clinically significant abnormalities on 12-lead electrocardiogram (ECG).
- •No other intercurrent medical conditions or infections considered clinically significant by the Investigator.
- •Clinical laboratory assessments are within the laboratory limits of normal values or not considered clinically significant by the Investigator.
- •Vitamin A levels at screening must be less than or equal to the upper limit of normal (ULN 95 µg/dL or 3.32 µmol/L).
- •Any male subject, if sexually active, agrees to use barrier contraceptive techniques as defined in the protocol. If female, the subject must be of non-childbearing potential as defined in the protocol.
- •Subjects who are active substances abusers may be enrolled at the discretion of the Principal Investigator.
- •Willing and able to provide written informed consent and comply with the study procedures and visit schedule, including follow up visits.
排除标准
- •Any disease or condition which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of ND L02 s0201, or would place the subject at increased risk.
- •On ongoing therapy for HCV/HBV, or received therapy for HCV/HBV within 12 weeks prior to administration of study drug.
- •On interferon therapy for any disease or received interferon therapy for any disease within 12 weeks prior to administration of study drug.
- •History of bone disease, including osteoporosis and osteomalacia, Paget's disease of bone, or a history of unexplained fractures or fractures after minimal trauma.
- •Alpha-fetoprotein (AFP) ≥ 50 ng/mL or signs of abnormality or hepatocellular carcinoma on ultrasound survey of the liver.
- •Carcinoembryonic antigen (CEA) levels above the ULN.
- •Laboratory test results include abnormal values considered to be clinically significant by the Investigator.
- •Participated in a concurrent interventional study with the last intervention occurring within 12 weeks prior to administration of study drug.
- •Taken vitamin A or vitamin D supplements or multi-vitamins that contain vitamin A or vitamin D between the screening visit and administration of study drug.
- •History, within the last 2 years, of alcohol abuse, significant mental illness, or physical dependence on any opioid.
- •Veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
- •Received recent treatment with alternative therapies, which, in the opinion of the Investigator, could potentially confound clinical or laboratory assessments.
- •Lost more than 500 mL of blood within 56 days prior to administration of study drug.
- •Body mass index (BMI) > 38 kg/m
- •History of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).
- •History of malignancy within the last 5 years with the exception of basal cell carcinoma.
- •Woman of childbearing potential.
- •History of hypersensitivity to H2-receptor antagonists.
- •Any other reason that, in the opinion of the Investigator or the Sponsor's Medical Monitor, makes the subject unsuitable for enrollment.
研究组 & 干预措施
Experimental: Arm A
Experimental
Once a week dosing
干预措施: ND-L02-s0201 Injection (Drug)
Experimental: Arm B
Experimental
Twice a week dosing
干预措施: ND-L02-s0201 Injection (Drug)
结局指标
主要结局
Number of participants with serious and non-serious adverse events
时间窗: After treatment for 5 consecutive weeks and follow-up through week 24
次要结局
未报告次要终点
研究者
研究点 (2)
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