A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Viremic Adult Subjects With Chronic Hepatitis B Who Are Not Currently on Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 10
- 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 and tolerability of multiple oral doses of selgantolimod and to evaluate the antiviral activity of selgantolimod in adult participants with chronic hepatitis B (CHB) who are viremic and not currently being treated.
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 male and non-pregnant, non-lactating females
- •Documented evidence of chronic hepatitis B virus (HBV) infection with detectable hepatitis B surface antigen (HBsAg) levels at screening
- •Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 international units per milliliter (IU/mL).
- •Screening electrocardiogram (ECG) without clinically significant abnormalities
排除标准
- •Extensive bridging fibrosis or cirrhosis
- •Received a commercially available HBV OAV treatment(s) within the 3 months prior to screening.
- •Received prolonged therapy with immunomodulators or biologics within 3 months of screening
- •Individuals meeting any of the following laboratory parameters at screening:
- •Alanine aminotransferase > 5 * upper limit of normal (ULN)
- •International normalized ratio > ULN unless the individual is stable on an anticoagulant regimen
- •Albumin < 3.5 g/dL
- •Direct bilirubin >1.5x ULN
- •Platelet Count < 100,000/µL
- •Estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault method)
- •Co-infection with human immunodeficiency virus (HIV), hepatitis C virus or hepatitis D virus
- •Prior history of hepatocellular carcinoma 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.
- •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 + TAF
Participants with Hepatitis B e antigen (HBeAg)-positive CHB or HBeAg-negative CHB currently not on oral antiviral (OAV) treatment, will receive selgantolimod 3 mg (2 x 1.5 mg tablet) on the same day once weekly for 24 doses along with tenofovir alafenamide (TAF) 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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 + TAF
Participants with Hepatitis B e antigen (HBeAg)-positive CHB or HBeAg-negative CHB currently not on oral antiviral (OAV) treatment, will receive selgantolimod 3 mg (2 x 1.5 mg tablet) on the same day once weekly for 24 doses along with tenofovir alafenamide (TAF) 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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: TAF (Drug)
Selgantolimod 1.5 mg + TAF
Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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 + TAF
Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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 + TAF
Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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: TAF (Drug)
Placebo + TAF
Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive 2 tablets of placebo on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, placebo will be discontinued, and participants will continue to receive TAF 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 + TAF
Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive 2 tablets of placebo on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, placebo will be discontinued, and participants will continue to receive TAF 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: TAF (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: Baseline, Week 24
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: First dose date up to Week 24 plus 30 days
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as any AE with an onset date on or after the first dose date and no later than 30 days after permanent discontinuation of selgantolimod/placebo; or any AE leading to premature discontinuation of study drugs.
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
时间窗: First dose date up to Week 24 plus 30 days
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 30 days for selgantolimod/placebo at Week 24. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Clinical laboratory results were graded according to Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.
次要结局
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12(Week 12)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 12(Week 12)
- Change From Baseline in Serum qHBsAg at Week 12(Baseline, Week 12)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8(Baseline, Week 8)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4(Baseline, Week 4)
- Change From Baseline in Serum qHBsAg at Week 48(Baseline, Week 48)
- Percentage of Participants With HBV DNA < LLOQ at Week 48(Week 48)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12(Baseline, Week 12)
- Change From Baseline in Serum qHBsAg at Week 4(Baseline, Week 4)
- Change From Baseline in Serum qHBsAg at Week 8(Baseline, Week 8)
- Percentage of Participants With HBsAg Loss at Week 48(Week 48)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 48(Week 48)
- Percentage of Participants With Drug Resistance Mutations(Baseline up to Week 48)
- PK Parameter: Tmax of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48(Baseline, Week 48)
- Change From Baseline in Serum qHBsAg at Week 24(Baseline, Week 24)
- Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12(Week 12)
- Percentage of Participants With HBV DNA < LLOQ at Week 24(Week 24)
- PK Parameter: AUC0-24 of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- PK Parameter: AUCinf of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- PK Parameter: CL/F of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- Percentage of Participants With HBsAg Loss at Week 24(Week 24)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 24(Week 24)
- Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24(Baseline up to Week 24)
- Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48(Baseline up to Week 48)
- PK Parameter: t1/2 of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)
- PK Parameter: Cmax of Selgantolimod(Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23)