A Randomized, Open-Label, Multicenter Study Investigating AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a Treatment in Subjects With Chronic Hepatitis B Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 32
- 主要终点
- The frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities after dosing with AB-729 plus Peg-IFNα-2a
研究概览
简要总结
This is a randomized, open label, multicenter Phase 2 study investigating the safety and antiviral activity of AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNα-2a in subjects with CHB.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic hepatitis B virus infection with documentation at least 6 months prior to screening
- •Subjects must have been receiving either TAF, TDF (or equivalent), or ETV consistently for ≥12 months prior to dosing Day 1
- •HBV DNA <LLOQ at Screening
- •HBsAg between 100 and 5,000 IU/mL at Screening
- •Subjects must be HBeAg-negative at Screening
- •Fibroscan® result of ≤8.5 kPa within 6 months prior to dosing Day 1
- •Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
排除标准
- •Evidence of co-infection with hepatitis A, C, D or E virus or human immunodeficiency virus (HIV) at screening
- •History of any clinically significant medical condition associated with chronic liver disease, cirrhosis, evidence of decompensated liver disease, or findings suggestive of hepatocellular carcinoma (HCC) at any time
- •Contraindications to the use of Peg-IFNα-2a or incapable of self-administration or assisted administration of Peg-IFNα-2a
- •Previous treatment with an experimental HBV-directed RNA-interference or antisense oligonucleotide product.
研究组 & 干预措施
Cohort A, Group 1
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.
干预措施: AB-729 (Drug)
Cohort A, Group 1
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.
干预措施: Peg-IFNα-2a (Drug)
Cohort A, Group 2
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.
干预措施: AB-729 (Drug)
Cohort A, Group 2
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks.
干预措施: Peg-IFNα-2a (Drug)
Cohort B, Group 1
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.
干预措施: AB-729 (Drug)
Cohort B, Group 1
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.
干预措施: Peg-IFNα-2a (Drug)
Cohort B, Group 2
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.
干预措施: AB-729 (Drug)
Cohort B, Group 2
AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to:
NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.
干预措施: Peg-IFNα-2a (Drug)
结局指标
主要结局
The frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities after dosing with AB-729 plus Peg-IFNα-2a
时间窗: Up to 124 weeks
The Frequency and Severity of Treatment Emergent Adverse Events (TEAEs), Discontinuations Due to AEs and Lab Abnormalities After Dosing With AB-729 Plus Peg-IFNα-2a
时间窗: Up to 124 weeks
次要结局
- Change from baseline in HBsAg and other virologic markers at each time point(Up to 124 weeks)
- Proportion of subjects who discontinue NA and subsequently restart NA therapy after meeting criteria(Up to 124 weeks)
- Proportion of subjects with HBsAb seroconversion at each timepoint(Up to 124 weeks)
- Proportion of subjects who are eligible to stop NA after Week 24 of follow up(Up to 76 weeks)
- Proportion of subjects who discontinue NA and subsequently meet protocol defined clinical relapse criteria. Proportion of subjects who discontinue NA and subsequently meet protocol defined viral relapse criteria(Up to 124 weeks)
- Post-dose plasma concentrations of AB-729 anti-sense (AS), AB-729 AS(N-1)3', and AB-729 AS(N-2)3' at selected timepoints(Up to 40 weeks)
- Proportion of Subjects Who Are Eligible to Stop NA After Week 24 of Follow up(Up to 76 weeks)
- Proportion of Subjects Who Discontinue NA and Subsequently Restart NA Therapy After Meeting Criteria(Up to 124 weeks)
- Change From Baseline in HBsAg and Other Virologic Markers at Each Time Point(Up to 124 weeks)
- Proportion of Subjects With HBsAb Seroconversion at Each Timepoint(Up to 124 weeks)
- Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Clinical Relapse Criteria. Proportion of Subjects Who Discontinue NA and Subsequently Meet Protocol Defined Viral Relapse Criteria(Up to 124 weeks)
- Post-dose Plasma Concentrations of AB-729 Anti-sense (AS), AB-729 AS(N-1)3', and AB-729 AS(N-2)3' at Selected Timepoints(Up to 40 weeks)