A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple- Dose Ranging, Adaptive Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Activity of GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 23
- 主要终点
- Assessment of adverse events in single and multiple oral doses of GS-9620
研究概览
简要总结
Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Dose escalation or repetition will be governed by pre-specified safety and activity rules. Subjects will be confined on either days 1-3 or days 1-3 and 8-10. Follow-up visits are also required periodically through day 43, and potential viral load follow-up visits at weeks 3 and 6 months post last dose. Study procedures involve blood draws for pharmacokinetic, pharmacodynamic, virologic, and safety assessments
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)
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
- •Chronic HBV infection ≥ 6 months
- •HBsAg ≥ 250 IU/mL
- •HBV treatment naïve
- •Absence of extensive bridging fibrosis (Metavir 3 or greater) or cirrhosis
- •Creatinine clearance ≥ 70 mL/min
排除标准
- •Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV
- •History of Gilberts disease
- •Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid-stimulating hormone (TSH), or other evidence of hepatic decompensation
- •Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease(COPD), malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed
- •Evidence of hepatocellular carcinoma
研究组 & 干预措施
0.3mg GS-9620
干预措施: Single Ascending Dose (SAD) Cohorts GS-9620 (Drug)
1mg GS-9620
干预措施: Single Ascending Dose (SAD) Cohorts GS-9620 (Drug)
2mg GS-9620
干预措施: Single Ascending Dose (SAD) Cohorts GS-9620 (Drug)
4mg GS-9620
干预措施: Single Ascending Dose (SAD) Cohorts GS-9620 (Drug)
0.3mg GS-9620 QW x 2 doses
干预措施: Multiple Ascending Dose (MAD) Cohorts (Drug)
1mg GS-9620 QW x 2 doses
干预措施: Multiple Ascending Dose (MAD) Cohorts (Drug)
2mg GS-9620 QW x 2 doses
干预措施: Multiple Ascending Dose (MAD) Cohorts (Drug)
4mg GS-9620 QW x 2 doses
干预措施: Multiple Ascending Dose (MAD) Cohorts (Drug)
结局指标
主要结局
Assessment of adverse events in single and multiple oral doses of GS-9620
时间窗: Periodically Through Week 25
Safety will be assessed during the study through the reporting of adverse events, by clinical laboratory tests, physical examinations including vital signs and ECGs at various time points during the study, and by documentation of concomitant medications throughout the study.
次要结局
- Reduction of hepatitis B (HBV) viral load from baseline(Up to Day 15 and Follow-Up)
- Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods(Day 1 and Day 8)
- Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs])(Up to Day 15)