A Randomized, Double-Blind, Active-Controlled Multicenter Phase 2 Study Evaluating the Efficacy and Safety of ALG-000184 Compared With Tenofovir Disoproxil Fumarate in Untreated HBeAg-Positive and HBeAg-Negative Adult Subjects With Chronic Hepatitis B Virus Infection (B-SUPREME)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 118
- 主要终点
- HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected)
研究概览
简要总结
This is a Phase 2 study to evaluate efficacy and safety of 48 weeks of oral once daily monotherapy with ALG-000184 versus tenofovir disproxil fumarate (TDF) for chronic HBV infection.
详细描述
This is a randomized, double-blind, active-controlled, multicenter Phase 2 study to evaluate the efficacy and safety of 48 weeks of oral (PO) once daily (QD) monotherapy with ALG-000184 versus TDF in treatment naive (TN) or currently not treated (CNT) HBeAg-positive and HBeAg-negative subjects with chronic HBV infection (inclusive of chronic infection and/or chronic hepatitis).
A total of approximately 200 eligible subjects will be enrolled across 2 study parts. Part 1 will be an evaluation of HBeAg-positive subjects with chronic HBV infection and Part 2 will be an evaluation of HBeAg-negative subjects with chronic HBV infection. Each study part will consist of a main study and an exploratory liver biopsy sub-study.
Following the 48-week double-blind dosing period (Week 48), all participating subjects (in Parts 1 and 2) will be allowed to roll over into a 48 week (i.e., Week 48-96) open-label treatment extension period where they will all receive ALG-000184 monotherapy.
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
- •Male or female between 18 and 65 years of age, with body mass index (BMI) of 18.0 to 35.0 kg/m2 (or minimun age by local regulatory requirements).
- •HBeAg-positive and anti-HBeAg (HBeAb) negative (Part 1); or HBeAg-negative (Part 2).
- •HBsAg ≥LLOQ.
- •HBV DNA ≥20,000 IU/mL.
- •A history of a clinical diagnosis of chronic HBV infection AND an ALT values of ≤8×ULN during screening.
- •Must have the following chronic hepatitis B virus infection treatment status at screening:
- •Have never received treatment with HBV antiviral medicines (NA, interferon) or investigational anti-HBV agents including a CAM [i.e., Treatment Naïve (TN) subjects], OR
- •Have not been on treatment with approved (NA, interferon) or investigational HBV antiviral medicines (e.g., antisense oligonucleotides or small interfering RNAs) within 6 months or 5 half-lives (whichever is longer) prior to randomization (i.e., Currently Not Treated (CNT) subjects).
排除标准
- •Co-infection with hepatitis A, C, D, E or HIV or any evidence of clinically significant liver disease of non-HBV etiology.
- •Positive for anti-HBs antibodies.
- •History or current evidence of cirrhosis.
- •Liver fibrosis that is classified as Metavir Score ≥F3 liver disease.
- •History of, or current evidence of, hepatic decompensation.
- •Evidence of hepatocellular carcinoma (HCC) on a liver ultrasound.
- •Having received an investigational medicinal product or device within 4 weeks (or 5 half-lives, whichever is longer) before the planned first dose of study drug
- •Exclusionary screening laboratory values include:
- •Aspartate aminotransferase (AST) >8×ULN,
- •Bilirubin (total, direct) >1.2×ULN (unless Gilbert's syndrome is suspected)
- •International Normalization Ratio (INR) >1.2×ULN
研究组 & 干预措施
TDF
Orally for 48 weeks followed by open-label treatment with ALG-000184 for 48 weeks.
干预措施: TDF (Drug)
ALG-000184
Orally for 48 weeks followed by open-label treatment with ALG-000184 for 48 weeks.
干预措施: ALG-000184 (Drug)
结局指标
主要结局
HBeAg positive: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target detected or target not detected)
时间窗: 48 weeks
HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target detected or target not detected) at Week 48
HBeAg negative: HBV DNA <Lower Limit of Quantification [LLOQ] (10 IU/mL, target not detected)
时间窗: 48 weeks
HBV DNA \<Lower Limit of Quantification \[LLOQ\] (10 IU/mL, target not detected) at Week 48
次要结局
- Safety and Tolerability(96 Weeks)
- HBV DNA levels(48 weeks)
- HBV DNA < lower limit of quantification [LLOQ] (target detected or target not detected) [HBeAg positive](48 weeks)
- HBV DNA < Lower Limit of Quantification [LLOQ] (target not detected) [HBeAg negative](48 weeks)
- Change in HBV DNA levels from baseline(48 weeks)
- Time to HBV DNA level <Lower Limit of Quantification [LLOQ](96 Weeks)
- Change in HBV RNA levels from baseline(48 weeks)
- Time to HBV RNA level <Lower Limit of Quantification [LLOQ](96 Weeks)
- Subjects with abnormal ALT at baseline who have normal ALT at Week 48(48 weeks)
- Emergence of treatment associated mutations in the HBV genome(96 Weeks)
- PK parameters of ALG-001075(96 Weeks)