A Phase 2, Randomized, Open-Label, Active-Controlled Study to Evaluate the Safety and Antiviral Activity of GS-9992 Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Chronic Hepatitis B (CHB) Subjects
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 123
- 试验地点
- 13
- 主要终点
- Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and tolerability of the 12 week treatment regimens of inarigivir soproxil plus tenofovir alafenamide (TAF) or commercially available nucleoside/nucleotide (NUC) in adults with chronic hepatitis B (CHB), to evaluate the antiviral activity of 12 weeks of inarigivir soproxil plus TAF versus TAF alone in viremic CHB participants (Groups 1-3, 5), and to evaluate the antiviral activity of 12 weeks of inarigivir soproxil with commercially available NUC(s) in virally suppressed CHB participants (Group 4).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Groups 1-3 and 5:
- •Individuals not taking any prescribed hepatitis B virus (HBV) NUC treatment
- •HBV deoxyribonucleic acid (DNA) ≤ 20 IU/mL at Screening by Central Lab.
- •Have been on a commercially available HBV NUC treatment(s)
排除标准
- •Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV).
- •Extensive bridging fibrosis or cirrhosis
- •Evidence of hepatocellular carcinoma on imaging
- •Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage).
- •Chronic liver disease of a non-HBV etiology
- •Current alcohol or substance abuse
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Group 1: Inarigivir Soproxil 50 mg + TAF
Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks.
干预措施: Inarigivir Soproxil (Drug)
Group 1: Inarigivir Soproxil 50 mg + TAF
Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks.
干预措施: TAF (Drug)
Group 2: TAF
Viremic participants will be administered TAF 25 mg tablet once daily orally with food for 48 weeks.
干预措施: TAF (Drug)
Group 3: Inarigivir Soproxil 200 mg + TAF
Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks
干预措施: Inarigivir Soproxil (Drug)
Group 3: Inarigivir Soproxil 200 mg + TAF
Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks
干预措施: TAF (Drug)
Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs
Virally suppressed participants receiving commercially available nucleoside/nucleotide (NUC) will be administered inarigivir soproxil 100 mg tablet once daily orally 1 hour before or 1 hour after a meal for 12 weeks. Participants will continue commercially available NUCs for 48 weeks.
干预措施: Inarigivir Soproxil (Drug)
Group 5: Inarigivir Soproxil 400 mg + TAF
Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks.
干预措施: Inarigivir Soproxil (Drug)
Group 5: Inarigivir Soproxil 400 mg + TAF
Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks.
干预措施: TAF (Drug)
结局指标
主要结局
Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)
时间窗: Baseline, Week 12
Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5)
时间窗: Baseline, Week 12
次要结局
- Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)(Baseline, Weeks 12, 16, 24, 36, and 48)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5)(Baseline, Week 12)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4)(Baseline, Week 12)
- Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)(Baseline, Weeks 12, 24, 36, and 48)
- Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4)(Baseline, Weeks 12, 24, 36, and 48)
- Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Had HBV DNA ≥ 69 IU/mL (Groups 1 Through 3 and 5)(Baseline, Week 48)
- Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4)(Baseline up to Week 12)
- Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5)(Baseline, Weeks 12, 24, 36, and 48)
- Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4)(Baseline, Weeks 12, 24, 36, and 48)
- Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5)(Baseline, Weeks 12, 16, 24, 36, and 48)
- Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4)(Baseline, Weeks 12, 16, 24, 36, and 48)