A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 12
- 主要终点
- Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
研究概览
简要总结
The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)
详细描述
This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B "e" antigen (HBeAg)-positive participants with cHBV.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Male or female between ages 18 and 70 years
- •HBeAg-positive at screening
- •In good general health except for cHBV
- •HBV viral load ≥2×105 IU/mL
- •Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening
排除标准
- •Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks
- •Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)
- •History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening
- •Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the participant unsuitable for the study
- •Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening
- •History of hepatocellular carcinoma (HCC)
- •Females who are lactating or pregnant or wish to become pregnant are excluded from the study
- •Exclusionary laboratory parameters at screening:
- •Platelet count <100,000/mm3
- •Albumin <lower limit of normal (LLN)
- •Direct bilirubin >1.2×upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) >10×ULN at screening
- •Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC
- •International Normalized Ratio (INR) >1.5×ULN
- •Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
研究组 & 干预措施
ABI-H0731 + SOC ETV
Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.
干预措施: ABI-H0731 (Drug)
ABI-H0731 + SOC ETV
Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.
干预措施: SOC ETV (Drug)
Placebo + SOC ETV
Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.
干预措施: SOC ETV (Drug)
Placebo + SOC ETV
Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
时间窗: Baseline, Week 12, and Week 24
Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.
次要结局
- Number of Participants One or More Adverse Events(Up to Follow-up (maximum up to Week 36))
- Number of Participants With Premature Study Discontinuation(Up to Follow-up (maximum up to Week 36))
- Number of Participants With One or More Abnormal Safety Laboratory Result(Up to Week 36)
- Number of Participants With a Clinically-significant Electrocardiogram Abnormality(Up to Week 24)
- Number of Participants With a Clinically-significant Change in Vital Signs(Baseline and up to Week 24)
- Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV(Baseline to Week 24)
- Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV(Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24)
- Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV(Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24)
- Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV(Up to Week 36)
- Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy(Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24)
- Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy(Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24)
- Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy(Baseline, Weeks 2, 4, 12, and 24)
- Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy(Baseline, Weeks 2, 4, 12, 24, and 28)