A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects With Chronic Hepatitis B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
研究概览
简要总结
The primary objectives of this study are to evaluate the safety, tolerability and antiviral activity of selgantolimod (formerly GS-9688) in virally suppressed chronic hepatitis B (CHB) adults on oral antiviral (OAV) agents.
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
- Double (Participant, 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
- •Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •Adult males and non-pregnant, non-lactating females
- •Documented evidence of chronic HBV infection with detectable hepatitis B surface antigen (HBsAg) levels
- •On commercially available HBV OAV treatment(s) for at least 6 months with no change in regimen for 3 months prior to screening
- •HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to screening
- •Screening Electrocardiogram (ECG) without clinically significant abnormalities
排除标准
- •Extensive bridging fibrosis or cirrhosis
- •Adults meeting any of the protocol defined exclusionary laboratory parameters at screening:
- •Alanine aminotransferase (ALT) > 3x Upper Limit of Normal (ULN)
- •International normalized ratio (INR) > ULN unless the adult is stable on an anticoagulant regimen
- •Albumin < 3.5 g/dL
- •Direct bilirubin > 1.5x ULN
- •Platelet Count < 100,000/uL
- •Estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault method)
- •Co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis D virus
- •Prior history of hepatocellular carcinoma (HCC) or screening alpha-fetoprotein ≥ 50 ng/mL without imaging
- •Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or are immunosuppressed.
- •Chronic liver disease of a non-HBV etiology, except for non-alcoholic fatty liver disease
- •Received solid organ or bone marrow transplant
- •Received prolonged therapy with immunomodulators or biologics within 3 months of screening
- •Use of another investigational agent within 90 days of screening, unless allowed by the Sponsor
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Selgantolimod 3 mg: HBeAg-positive CHB Participants
Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks.
干预措施: Selgantolimod (Drug)
Selgantolimod 3 mg: HBeAg-positive CHB Participants
Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
Selgantolimod 3 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Selgantolimod (Drug)
Selgantolimod 3 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Selgantolimod (Drug)
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Placebo (Drug)
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Selgantolimod (Drug)
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Placebo (Drug)
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
Placebo: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Placebo (Drug)
Placebo: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
Placebo: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Placebo (Drug)
Placebo: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
干预措施: Hepatitis B virus (HBV) OAV Therapy (Drug)
结局指标
主要结局
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
时间窗: Week 24
次要结局
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4(Week 4)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8(Week 8)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12(Week 12)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48(Week 48)
- Change From Baseline in Serum qHBsAg at Week 4(Baseline, Week 4)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 12(Week 12)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8(Baseline, Week 8)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12(Baseline, Week 12)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24(Baseline, Week 24)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48(Baseline, Week 48)
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12(Week 12)
- Percentage of Participants With HBsAg Loss at Week 24(Week 24)
- Percentage of Participants With HBsAg Loss at Week 48(Week 48)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 24(Week 24)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 48(Week 48)
- Percentage of Participants With Virologic Breakthrough(Baseline up to Week 48)
- Percentage of Participants With Drug Resistance Mutations(Baseline up to Week 48)