A Multicenter, Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Combination With Entecavir or Tenofovir in Patients With Chronic Hepatitis B Virus (HBV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Percentage of Initial Responders to ARC-520 Therapy Achieving a 1-log Reduction in HBsAg at Week 36 Compared to Baseline
研究概览
简要总结
Chronic HBV patients will receive 9 doses of open-label ARC-520 once every 4 weeks and be evaluated for safety and efficacy.
详细描述
Open-label, multi-center extension study of intravenous ARC-520 in combination with entecavir or tenofovir in patients with chronic HBV infection. Patients who successfully completed the Heparc-2002 (NCT02604199) and Heparc-2003 (NCT02604212) studies and responded to therapy are eligible to participate. Responders are defined as patients who showed a ½ log or greater reduction in their serum Hepatitis B Surface Antigen (HBsAg) levels from baseline to day 71 ± 3 days of the primary Heparc-2002 and Heparc-2003 studies. Patients who have signed a Human Research Ethics Committee approved informed consent and have met all of the protocol eligibility criteria will continue receiving daily oral entecavir or tenofovir and intravenous (IV) injections of ARC-520. Study visits will occur once every 4 weeks for a total of 9 visits for monitoring and ARC-520 administration.
Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate and temperature), weight, adverse events (AEs), 12-lead electrocardiograms (ECGs), concomitant medications, blood sample collection for hematology, coagulation, chemistry, creatine kinase, troponin, hemoglobin A1c, exploratory pharmacodynamic (PD) measures, urinalysis, HBV serology, immunogenicity, and pregnancy testing for females of childbearing potential. Patients will be monitored for HBV virology, AEs, and exploratory PD measures for a total of 24 weeks after the last dose of ARC-520.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient showed a ½ log or greater reduction in serum HBsAg levels from baseline to Day 71 ± 3 days or Day 99 ± 3 days in the primary Heparc-2002 or Heparc-2003 study.
- •Able to have first dose within 2 months of day 113 end-of-study visit in the primary Heparc-2002 or Heparc-2003 study.
- •Able to provide written informed consent prior to the performance of any study specific procedures.
- •Have no abnormalities in 12-lead ECG assessment that, in the opinion of the investigator, may compromise patient safety
- •Willing and able to comply with all study assessments and adhere to the protocol schedule.
- •Have no new abnormal finding of clinical relevance at the screening evaluation.
- •Using 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners) during the study and for 3 months following the last dose of (ARC 520).
排除标准
- •Pregnant or lactating.
- •Acute signs of hepatitis/other infection within 4 weeks of screening and/or at the screening examination.
- •Use of prescription medication (including anticoagulants) within 14 days prior to administration of ARC-
- •Has had major surgery within 3 months of screening.
- •Has evidence of severe systemic acute inflammation, sepsis, or hemolysis.
- •Diagnosed with a significant psychiatric disorder that would prevent participation in the study.
- •Unable or unwilling to return for all scheduled study visits.
- •Has any other condition that, in the opinion of the investigator, would render the patient unsuitable for enrollment, or could interfere with his/her participation in the study.
研究组 & 干预措施
ARC-520 Injection
Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
干预措施: ARC-520 Injection (Drug)
ARC-520 Injection
Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
干预措施: entecavir (Drug)
ARC-520 Injection
Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
干预措施: tenofovir (Drug)
ARC-520 Injection
Multiple administrations of ARC-520 starting at a dose level of 2 mg/kg, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
干预措施: antihistamine (Drug)
结局指标
主要结局
Percentage of Initial Responders to ARC-520 Therapy Achieving a 1-log Reduction in HBsAg at Week 36 Compared to Baseline
时间窗: Baseline, Week 36
Initial responders are defined as participants who showed a ½ log or greater reduction in their serum HBsAg levels from baseline to Day 71 ± 3 days of the primary Heparc-2002 and Heparc-2003 studies, where baseline is defined as the average of pre-dose values.
次要结局
- Percentage of Initial Responders to ARC-520 Therapy With HBsAg Loss (Qualitative) Compared to Baseline Over Time(Baseline, Weeks 36, 48, and 60)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug up to 28 weeks of treatment, plus up to 24 weeks of follow-up)