A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 31
- 主要终点
- Mean Change in Serum HBsAg From Baseline to Week 24
研究概览
简要总结
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a treatment extension for 96 weeks.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study
- •Documented evidence of chronic hepatitis B virus (HBV) infection, for example, hepatitis B surface antigen (HBsAg) positive for more than 6 months
- •Screening HBV DNA ≥ 2000 IU/mL
- •A negative serum pregnancy test is required for females (unless surgically sterile or > 2 years post-menopausal)
排除标准
- •Cirrhosis
- •Inadequate liver function
- •Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)
- •Received antiviral treatment for HBV within 3 months of screening
- •Evidence of hepatocellular carcinoma (eg, as evidenced by recent imaging)
- •Significant cardiovascular, pulmonary, or neurological disease
- •Women who are pregnant or may wish to become pregnant during the course of the study
- •Received solid organ or bone marrow transplant
- •Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, interferon) within 3 months of screening
- •Use of investigational agents within 3 months of screening
- •Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
- •Receipt of immunoglobulin or other blood products within 3 months prior to enrollment
- •History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease, Ulcerative colitis, or autoimmune disease
- •Documented history of yeast allergy
- •Known hypersensitivity to study drugs, metabolites or formulation excipients
- •Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Individuals under evaluation for possible malignancy are not eligible
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
TDF 48 weeks
Participants will receive TDF for 48 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: Tenofovir disoproxil fumarate (Drug)
TDF plus GS-4774 2 YU
Participants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: Tenofovir disoproxil fumarate (Drug)
TDF plus GS-4774 2 YU
Participants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: GS-4774 (Biological)
TDF plus GS-4774 10 YU
Participants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: Tenofovir disoproxil fumarate (Drug)
TDF plus GS-4774 10 YU
Participants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: GS-4774 (Biological)
TDF plus GS-4774 40 YU
Participants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: Tenofovir disoproxil fumarate (Drug)
TDF plus GS-4774 40 YU
Participants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.
干预措施: GS-4774 (Biological)
结局指标
主要结局
Mean Change in Serum HBsAg From Baseline to Week 24
时间窗: Baseline to Week 24
The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included treatment groups, ALT levels (\> ULN or ≤ ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% confidence intervals (CIs).
次要结局
- Mean Change in HBsAg From Baseline to Week 12(Baseline to Week 12)
- Mean Change in HBsAg From Baseline to Week 48(Baseline to Week 48)
- Percentage of Participants With HBsAg Loss at Week 24(Baseline to Week 24)
- Percentage of Participants With HBsAg Loss at Week 48(Baseline to Week 48)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24(Baseline to Week 24)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48(Baseline to Week 48)
- Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 12(Baseline to Week 12)
- Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 24(Baseline to Week 24)
- Percentage of Participants With a ≥ 0.5 Log10 IU/mL or a ≥ 1.0 Log10 IU/mL Decline in HBsAg at Week 48(Baseline to Week 48)
- Percentage of Participants With HBeAg Loss at Week 24(Baseline to Week 24)
- Percentage of Participants With HBV DNA < Lower Limit of Quantification (LLOQ) at Week 24(Week 24)
- Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 48(Baseline to Week 48)
- Percentage of Participants With HBeAg Loss at Week 48(Baseline to Week 48)
- Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 24(Baseline to Week 24)
- Percentage of Participants With HBV DNA < LLOQ at Week 48(Week 48)
- Percentage of Participants Experiencing Virologic Breakthrough at Week 24(Baseline to Week 24)
- Percentage of Participants Experiencing Virologic Breakthrough at Week 48(Baseline to Week 48)
- Number of Participants With Drug-Resistance Mutations at Week 48 or at the Last Visit Available(Baseline to Week 48)