A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AB-836, an HBV Capsid Inhibitor, in Healthy Subjects and Subjects With Chronic HBV Infection
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 110
- 试验地点
- 15
- 主要终点
- Incidence of TEAEs
研究概览
简要总结
This three-part, Phase 1 protocol will be the first clinical study of AB-836. Parts 1 and 2a/b will be a Phase 1a SAD/MAD of AB-836 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-836 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.
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, Care Provider, Investigator)
盲法说明
Single blind only (Participant) in Part 2b
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
- •Healthy Subjects
- •Male and Female (not of childbearing potential in Part 1 and 2a) subjects between 18 and 45 years old
- •Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.
- •BMI of 18-32 kg/m
- •CHB Subjects:
- •Male or female between 18 and 65 years old.
- •Chronic HBV infection documented as a positive HBsAg, HBV DNA, or HBeAg test at least 6 months prior to the Screening Visit, or a historical liver biopsy consistent with chronic HBV infection
- •For cohort F, G, H:
- •HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment).
- •ALT ≤ 5x ULN
- •For Cohort I:
- •HBV DNA <LLOQ at Screening
- •Subjects must have been receiving either TAF, TDF, or ETV consistently for ≥6 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit.
- •ALT ≤ 2.5 x ULN
- •HbsAg ≥250 IU/mL at screening
排除标准
- •CHB Subjects
- •Advanced fibrosis, cirrhosis or other signs of advanced liver disease as assessed by clinical history, ultrasound or FibroScan, or history of cirrhosis or any clinically significant medical condition associated with chronic liver disease.
- •Co-infection with HIV or other non-B hepatitis viruses.
- •Any clinically significant or unstable medical condition or illness that could confound study findings.
- •Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding.
- •Previous treatment with a capsid inhibitor, core inhibitor, or core protein assembly modifier [CpAM or CAM]) within 6 months of the Day 1 visit, or prior treatment with an HBV-targeted siRNA or antisense oligonucleotide compound at any time.
研究组 & 干预措施
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I
Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.
干预措施: Nucleos(t)ide Analogue (Drug)
Part 1 (Healthy Subjects): Single Ascending Dose (SAD)
Two cohorts (Cohorts A and B) of healthy subjects will receive single doses of AB-836/placebo in an alternating cohort design under fasted conditions. One additional treatment will be administered under fed conditions.
干预措施: AB-836 (Drug)
Part 1 (Healthy Subjects): Single Ascending Dose (SAD)
Two cohorts (Cohorts A and B) of healthy subjects will receive single doses of AB-836/placebo in an alternating cohort design under fasted conditions. One additional treatment will be administered under fed conditions.
干预措施: Placebo (Drug)
Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD)
Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days
干预措施: AB-836 (Drug)
Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD)
Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days
干预措施: Placebo (Drug)
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H
Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.
干预措施: AB-836 (Drug)
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H
Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.
干预措施: Placebo (Drug)
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I
Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.
干预措施: AB-836 (Drug)
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I
Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.
干预措施: Placebo (Drug)
Part 2b (Healthy Subjects): MAD
Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days
干预措施: AB-836 (Drug)
Part 2b (Healthy Subjects): MAD
Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of TEAEs
时间窗: Up to 35 days after last dose of AB-836/placebo
Incidence of discontinuations due to AEs
时间窗: Up to 35 days after last dose of AB-836/placebo
Incidence of lab abnormalities
时间窗: Up to 35 days after last dose of AB-836/placebo
次要结局
未报告次要终点