A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 19
- 主要终点
- Change in serum hepatitis B virus (HBV) DNA
研究概览
简要总结
This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil fumarate (TDF).
详细描述
This is a randomized, open-label, active-controlled study whose primary objective is to evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be between 18 and 65 years of age
- •Must have Screening plasma HBV DNA ≥ 2x10^3 IU/mL
- •Must have chronic HBV infection for at least 6 months
- •Must have estimated creatinine clearance (CLCr) ≥ 70 mL/min
- •Not pregnant or nursing
- •Women must be of non-childbearing potential OR of childbearing potential with confirmed negative pregnancy tests
- •Consistent and correct use of recommended methods of birth control for men and women
排除标准
- •Pregnant or lactating subjects
- •Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study screening
- •Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
- •Presence of autoimmune disorders
- •History of liver disease other than Hepatitis B
- •History of Gilbert's Disease
- •Any sign of decompensated liver disease
- •Known or suspected cirrhosis
- •Evidence of hepatocellular carcinoma
- •Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
- •Electrolyte abnormalities
- •History of treatment that permanently alters the gastric condition
- •Alcohol or substance abuse
- •History of bleeding diathesis
- •Significant bone disease
研究组 & 干预措施
GS-7340 8mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
干预措施: GS-7340 (Drug)
GS-7340 25mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
干预措施: GS-7340 (Drug)
GS-7340 40mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
干预措施: GS-7340 (Drug)
GS-7340 120mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
干预措施: GS-7340 (Drug)
Tenofovir disoproxil fumarate 300mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
干预措施: Tenofovir disoproxil fumarate (Drug)
结局指标
主要结局
Change in serum hepatitis B virus (HBV) DNA
时间窗: Up to Week 4
Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg.
次要结局
- Change in HBV DNA of GS-7340 through 28 days of therapy(Up to week 4)
- Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF(Up to week 4)
- Safety and Tolerability of Therapy(Up to week 4)
- Change in HBV DNA for tenofovir disoproxil fumarate (TDF)(Up to Week 4)