A Phase 2a Single-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety, Anti Viral Activity, and Pharmacokinetics of ARB-001467 in Non Cirrhotic, HBeAg Negative and Positive Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment.
研究概览
简要总结
The study is a phase 2a, single blind, randomized, placebo controlled, study evaluating the safety, anti-viral activity, and pharmacokinetics (PK) following multiple doses of intravenous ARB-001467
详细描述
Approximately 24 subjects will be enrolled in three cohorts: two cohorts of HBeAg-negative subjects and one cohort of HBeAg-positive subjects and 12 HbeAg-negative subjects will be enrolled in cohort 4. All subjects will be non-cirrhotic, with chronic hepatitis B virus (HBV) infection, and will have been receiving nucleos(t)ide-analogue (NA) therapy with entecavir or tenofovir for at least 12 months.
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
- Single (Participant)
盲法说明
Single Blind (Subject) in cohort 1-3, Open label in Cohort 4
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented chronic HBV infection for ≥12 months prior to Screening Visit.
- •Quantitative HBsAg ≥1000 IU/mL at the Screening Visit.
- •Subjects currently receiving entecavir and/or tenofovir for ≥12 months and HBV DNA undetectable.
排除标准
- •Known co-infection with HIV, hepatitis C virus, and hepatitis D virus.
- •Receiving or planning to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first dose of study treatment.
- •Receiving or planning to receive interferon during the study or ≤12 months prior to the first dose of study treatment.
- •Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
- •Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior to the Screening Visit.
- •Any known pre-existing medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings.
研究组 & 干预措施
0.2 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months
干预措施: ARB-001467 (Drug)
0.2 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months
干预措施: Placebo (Other)
0.4 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
干预措施: ARB-001467 (Drug)
0.4 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
干预措施: Placebo (Other)
ARB-001467 or Placebo
HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
干预措施: ARB-001467 (Drug)
ARB-001467 or Placebo
HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
干预措施: Placebo (Other)
0.4 mg/kg ARB-001467
HBeAg-negative subjects receive ARB-001467 at. 0.4 mg/kg (open label) bi-weekly for 5 treatments and then subjects with HBsAg ≤1000 IU/mL AND ≥1.0 log10 decrease from baseline at Day 71 will continue monthly dosing through 48 weeks
干预措施: ARB-001467 (Drug)
结局指标
主要结局
Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment.
时间窗: 28 days post last infusion
To evaluate the safety and tolerability of multiple doses of ARB-001467 in HBeAg-negative and HBeAg-positive subjects with chronic Hepatitis B virus infection who are receiving nucleos(t)ide analogue therapy
次要结局
- Evaluate additional parameters for ARB-001467 from plasma concentration-time curve from start of infusion and extrapolated to infinity (AUC0-t), inf) partial, AUCs, T1/2, volume of distribution (VD) and clearance (CL) -baseline through Day 85 or Week 36.(Up to 36 Weeks)
- Evaluate ARB-001467 Maximum plasma concentration (Cmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).(Up to 36 Weeks)
- Evaluate ARB-001467 Time to maximum plasma concentration (Tmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).(Up to 36 Weeks)
- Evaluate ARB-001467 Area under the plasma concentration-time curve from the start of infusion to the last measurable concentration (AUC0-t) at multiple time points from baseline through Day 85 (cohort 1-3) and Week 36 (Cohort 4).(Up to 36 Weeks)
- Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.(Up to 18 months)