A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 162
- 主要终点
- Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at 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 vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).
Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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 have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- •Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening
- •Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening
- •Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
- •Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
- •Must be willing and able to comply with all study requirements
排除标准
- •Extensive bridging fibrosis or cirrhosis
- •Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
- •Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
- •Evidence of hepatocellular carcinoma
- •Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
- •Significant cardiovascular, pulmonary, or neurological disease
- •Any of the following conditions that may worsen in response to interferon (IFN):
- •Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis)
- •Poorly controlled diabetes mellitus
- •Significant psychiatric disorders
- •Thyroid disorder (unless controlled under treatment)
- •Significant pulmonary diseases (eg, chronic obstructive pulmonary disease)
- •Retinal disease
- •Immunodeficiency disorders
- •Received solid organ or bone marrow transplant
- •Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening
- •Use of another investigational agents within 3 months of screening
- •Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
- •Females who are pregnant or may wish to become pregnant during the study
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Vesatolimod 4 mg 4 Weeks (Cohort A)
Vesatolimod 4 mg tablet once a week for 4 weeks
干预措施: Vesatolimod (Drug)
Placebo 4 Weeks (Cohort A)
Placebo tablet once a week for 4 weeks
干预措施: Placebo (Drug)
Vesatolimod 1 mg 4 Weeks (Cohort A)
Vesatolimod 1 mg tablet once a week for 4 weeks
干预措施: Vesatolimod (Drug)
Vesatolimod 2 mg 4 Weeks (Cohort A)
Vesatolimod 2 mg tablet once a week for 4 weeks
干预措施: Vesatolimod (Drug)
Placebo 8 Weeks (Cohort B)
Placebo tablet once a week for 8 weeks
干预措施: Placebo (Drug)
Vesatolimod 1 mg 8 Weeks (Cohort B)
Vesatolimod 1 mg tablet once a week for 8 weeks
干预措施: Vesatolimod (Drug)
Vesatolimod 2 mg 8 Weeks (Cohort B)
Vesatolimod 2 mg tablet once a week for 8 weeks
干预措施: Vesatolimod (Drug)
Vesatolimod 4 mg 8 Weeks (Cohort B)
Vesatolimod 4 mg tablet once a week for 8 weeks
干预措施: Vesatolimod (Drug)
Placebo 12 Weeks (Cohort C)
Placebo tablet once a week for 12 weeks
干预措施: Placebo (Drug)
Vesatolimod 1 mg 12 Weeks (Cohort C)
Vesatolimod 1 mg tablet once a week for 12 weeks
干预措施: Vesatolimod (Drug)
Vesatolimod 2 mg 12 Weeks (Cohort C)
Vesatolimod 2 mg tablet once a week for 12 weeks
干预措施: Vesatolimod (Drug)
Vesatolimod 4 mg 12 Weeks (Cohort C)
Vesatolimod 4 mg tablet once a week for 12 weeks
干预措施: Vesatolimod (Drug)
结局指标
主要结局
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
时间窗: Baseline to Week 24
A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (\> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
次要结局
- Change From Baseline in Serum HBsAg Level at Week 12(Baseline; Week 12)
- Change From Baseline in Serum HBsAg Level at Week 48(Baseline; Week 48)
- Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24(Week 24)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24(Week 24)
- Change From Baseline in Serum HBsAg Level at Week 4(Baseline; Week 4)
- Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48(Week 48)
- Change From Baseline in Serum HBsAg Level at Week 8(Baseline; Week 8)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48(Week 48)