A Phase 1/2a Single Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-HBV in Normal Adult Volunteers and Multiple Escalating Doses Evaluating Safety, Tolerability and Pharmacodynamic Effects in HBV Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 7
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).
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
- 未提供
排除标准
- •Clinically significant health concerns (with the exception of HBV for Patients in Part B)
- •Abnormal for any clinical safety laboratory result considered clinically significant
- •Regular use of alcohol within 1 month prior to screening
- •Recent use of illicit drugs
- •Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
- •NOTE: additional inclusion/exclusion criteria may apply, per protocol
研究组 & 干预措施
ARO-HBV 50 mg Q28D
ARO-HBV 50 mg sc injection Q28D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 100 mg Q28D
ARO-HBV 100 mg sc injection Q28D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 200 mg Q28D
ARO-HBV 200 mg sc injection Q28D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 35 mg
Single dose of ARO-HBV 35 mg subcutaneous (sc) injection in normal healthy volunteers
干预措施: ARO-HBV (Drug)
ARO-HBV 100 mg
Single dose of ARO-HBV 100 mg sc injection in normal healthy volunteers
干预措施: ARO-HBV (Drug)
ARO-HBV 200 mg
Single dose of ARO-HBV 200 mg sc injection in normal healthy volunteers
干预措施: ARO-HBV (Drug)
ARO-HBV 300 mg
Single dose of ARO-HBV 300 mg sc injection in normal healthy volunteers
干预措施: ARO-HBV (Drug)
ARO-HBV 400 mg
Single dose of ARO-HBV 400 mg sc injection in normal healthy volunteers
干预措施: ARO-HBV (Drug)
Placebo
Sterile normal saline (0.9% NaCl) sc injection in normal healthy volunteers
干预措施: Sterile Normal Saline (0.9% NaCl) (Other)
ARO-HBV 25 mg, Q28D
ARO-HBV 25 mg sc injection every 28 days (Q28D) in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 300 mg Q28D
ARO-HBV 300 mg sc injection Q28D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 400 mg Q28D
ARO-HBV 400 mg sc injection Q28D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 100 mg Q14D
ARO-HBV 100 mg sc injection every 14 days (Q14D) in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 100 mg Q7D
ARO-HBV 100 mg sc injection every 7 days (Q7D) in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 300 mg, Q28D, HBeAg+/ Trt Naïve
ARO-HBV 300 mg sc injection Q28D in hepatitis B e antigen positive/treatment naïve (HBeAg+/Trt Naïve) participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 300 mg, Q28D, HBeAg+/ NUC
ARO-HBV 300 mg sc injection Q28D in HBeAg+/nucleotide or nucleoside analog treated (HBeAg+/NUC) participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 200 mg, Q7D
ARO-HBV 200 mg sc injection Q7D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 300 mg, Q7D
ARO-HBV 300 mg sc injection Q7D in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 200 mg Q28D + JNJ-56136379 250 mg
ARO-HBV 200 mg sc injection Q28D plus JNJ-56136379 250 mg in participants with chronic hepatitis B
干预措施: ARO-HBV (Drug)
ARO-HBV 200 mg Q28D + JNJ-56136379 250 mg
ARO-HBV 200 mg sc injection Q28D plus JNJ-56136379 250 mg in participants with chronic hepatitis B
干预措施: JNJ-56136379 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Possibly or Probably Related to Treatment
时间窗: NHV participants: up to Day 29 (± 2 days); CHB participants: Day 113 (± 2 days)
An adverse event (AE) is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. Assessment of causality utilized 3 possible categories: not related, possibly related and probably related.
次要结局
- Part A, PK of ARO-HBV Analytes : Time to Maximum Plasma Concentration (Tmax)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Terminal Elimination Half-Life (t½)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-24(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Dose-Normalized AUC0-t(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Dose-Normalized Cmax(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Change From Baseline in HBV Surface Antigen (HBsAg) From Day 1 Pre-Dose Baseline to Post-Dose Nadir in Participants Chronically Infected With HBV(Part B (multiple-ascending dose [MAD] phase) only: up to 113 days)
- Part A, Pharmacokinetics (PK) of ARO-HBV Analytes: Maximum Observed Plasma Concentration (Cmax)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)
- Part A, PK of ARO-HBV Analytes: Area Under the Plasma Concentration Versus Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUC0-t)(Day 1: 0 (pre-dose), 15 minutes, 0.5, 1, 2, 3, 6, 24 & 48 hours post-dose)