NCT03125213撤回2 期
A Phase 2a, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics of AL-3778 in Combination With Peginterferon Alpha-2a in Treatment Naïve Chronic Hepatitis B Subjects Who Are HBeAg-positive
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.
研究概览
简要总结
This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, efficacy, and pharmacokinetics (PK) of AL-3778 in combination with Peg-IFN in subjects with Hepatitis B e antigen (HBeAg) positive CHB virus infection who are treatment-naïve.
The study will consist of a screening phase , a double-blind treatment phase followed by treatment with Peg-IFN alone, and a post-treatment follow-up phase.
Approximately 30 subjects to complete the study. Eligible subjects will be randomized into 2 treatment arms in a 2:1 ratio (active:placebo) to receive one of the following treatments:
- Arm A: Peg-IFN plus AL-3778 (N=20)
- Arm B: Peg-IFN plus matching placebo (N=10)
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •A female subject must be of non-childbearing potential
- •Subjects must have CHB infection, documented by serologic profile consistent for CHB infection at screening:
- •serum HBsAg positive (for >6 months)
- •serum IgM anti-HBc negative
- •Subjects are treatment-naïve and are serum HBeAg positive with:
- •serum HBV DNA >=20,000 IU /mL at screening
- •HBsAg >250 IU/mL at screening
- •≥2× upper limit of normal (ULN) ALT and ≤5× ULN at screening
排除标准
- •Positive test for hepatitis A virus immunoglobulin, hepatitis delta antibody (Ab), hepatitis C Ab, human immunodeficiency virus (HIV) Ab and/or evidence of clinically relevant active infection that would interfere with study conduct or its interpretation would also lead to exclusion.
- •Positive test for anti-HBs antibodies and anti-HBe antibodies.
- •Subjects must have low levels of liver fibrosis that is classified as Metavir F0-F2
- •Any history or current evidence of hepatic decompensation
- •Subjects must have absence of hepatocellular carcinoma
- •Subject with evidence of retinopathy on retinal fundus photographs
- •Exclusions related to interferon use for the purposes of this study
- •Subjects with one or more of the following laboratory abnormalities at screening
- •serum creatinine elevation >1.0× ULN
- •hemoglobin <11 g/dL [males], <10.5 g/dL [females]
- •platelet count <125× 109 cells/L
- •absolute neutrophil count <1.0× 109 cells/L
- •total bilirubin >1.0× ULN; unless known Gilbert's Disease or Dubin-Johnson Syndrome
- •Subjects having received an investigational agent or investigational vaccine, or having received a biological product within 12 weeks or 5 half-lives (whichever is longer) prior to baseline (first intake of study drugs).
研究组 & 干预措施
Peg-IFN plus AL-3778
Active Comparator
干预措施: AL-3778 (Drug)
Peg-IFN plus AL-3778
Active Comparator
干预措施: Peginterferon Alfa-2A (Drug)
Peg-IFN plus matching placebo
Placebo Comparator
干预措施: Peginterferon Alfa-2A (Drug)
Peg-IFN plus matching placebo
Placebo Comparator
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Mean change (measured in log10 IU/mL) in serum HBsAg from baseline at Week 24.
时间窗: Day 1 to Week 24
次要结局
- Individually derived Bayesian estimates of AL-3778 Steady state plasma concentration (C0h)(Week 2)
- Individually derived Bayesian estimates of AL-3778 area under the plasma concentration curve vs time (AUC0-12h)(Week 2)
- Proportion of subjects with ALT normalization(Day 1 to Week 72)
- Incidence and severity of hepatic flares on treatment(Day 1 to Week 48)
- Incidence and severity of hepatic flares off-treatment.(Week 48 to week 72)
- Proportions of subjects with HBeAg loss and/or seroconversion.(Day 1 to Week 72)
- Proportions of subjects with HBsAg loss and/or seroconversion.(Day 1 to Week 72)
- Changes in serum HBsAg and serum HBeAg levels over time.(Day 1 to Week 72)
- Proportion of subjects experiencing a viral breakthrough on treatment.(Day 1 to Week 48)
- Assess emergence of treatment-associated mutations during study treatment and follow-up with a focus on subjects with treatment failure(Day 1 to Week 72)
- Incidence and severity of AEs(Screening to Week 72)
- Incidence and severity of laboratory abnormalities(Screening to Week 72)
- Incidence of serious adverse events (SAEs).(Screening to Week 72)
- Incidence and severity of AEs leading to study drug discontinuation.(Screening to Week 72)
- Changes in serum HBV DNA over time(Day 1 to Week 72)
- AL-3778 maximum observed plasma concentration (Cmax)(Week 2)
- AL-3778 Steady state plasma concentration (C0h)(Week 2)
- AL-3778 area under the plasma concentration curve vs time (AUC0-12h)(Week 2)
研究者
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