A Multicenter, Randomized, Double-blind, Placebo-controlled, Multi-dose Study to Determine the Depth of Hepatitis B Surface Antigen (HBsAg) Reduction Following Intravenous ARC-520 in Combination With Entecavir or Tenofovir in Patients With HBeAg Positive, Chronic Hepatitis B Virus (HBV) Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 4
- 主要终点
- Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85
研究概览
简要总结
Participants with chronic HBV infection will receive multiple doses of ARC-520 in combination with entecavir or tenofovir and be evaluated for safety and efficacy.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 to 75 years of age
- •Written informed consent
- •Body mass index (BMI) between 17.5 and 30.0 kg/m2
- •No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
- •No abnormal finding of clinical relevance
- •Diagnosis of HBeAg positive, immune active, chronic HBV infection
- •> 2 months of continuous treatment with daily oral entecavir or tenofovir
- •Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive)
排除标准
- •Pregnant or lactating
- •Acute signs of hepatitis/other infection within 4 weeks of screening
- •Hepatic transaminases (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) > 3 times the upper limits of normal
- •Liver Elastography (i.e. FibroScan®) score > 9
- •Antiviral therapy other than entecavir or tenofovir within 3 months of screening
- •Prior treatment with interferon in the last 3 years
- •Use of anticoagulants, corticosteroids, immunomodulators, or immunosuppressants within 6 months of screening
- •Use within 7 days prior to screening of dietary and/or herbal supplements that can interfere with liver metabolism
- •Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days of study drug administration
- •Use of prescription medication within 14 days prior to study drug administration
- •Depot injection/implant of any drug except birth control within 3 months prior to study drug administration
- •Known diagnosis of diabetes mellitus
- •History of autoimmune disease
- •Human immunodeficiency virus (HIV) infection
- •Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis
- •Hypertension; blood pressure > 150/100 mmHg
- •History of cardiac rhythm disturbances
- •Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death
- •Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry
- •History of malignancy, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, in situ cervical cancer
- •Major surgery within 3 months of screening
- •History of alcohol and/or drug abuse < 12 months from screening
- •Regular use of alcohol within 6 months (ie, more than 14 units of alcohol per week)
- •Evidence of systemic acute inflammation, sepsis, or hemolysis
- •Diagnosed with a significant psychiatric disorder
- •Use of drugs of abuse
- •History of allergy to bee venom
- •Positive reaction to the bee venom allergy immunoglobulin E (IgE) test
- •Use of investigational agents or devices within 30 days
- •Clinically significant inherited or acquired gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease
- •Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction
- •Clinically significant history or presence of uncontrolled systemic disease
- •Donated or had a loss of whole blood of 50 milliliters (mL) to 499 mL within 30 days or more than 499 mL between 31 and 56 days prior to study treatment
- •History of fever within 2 weeks of screening
- •Immunization/planned immunization with live attenuated vaccine except influenza vaccine
- •Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk
- •Excessive exercise/physical activity within 7 days of screening/enrolment or during study
- •History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s)
研究组 & 干预措施
ARC-520
Intravenous administration of 1.0 mg/kg ARC-520 once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of study drug.
干预措施: ARC-520 (Drug)
ARC-520
Intravenous administration of 1.0 mg/kg ARC-520 once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of study drug.
干预措施: Entecavir (Drug)
ARC-520
Intravenous administration of 1.0 mg/kg ARC-520 once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of study drug.
干预措施: Tenofovir (Drug)
ARC-520
Intravenous administration of 1.0 mg/kg ARC-520 once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of study drug.
干预措施: diphenhydramine (Drug)
Placebo
Intravenous administration of normal saline (0.9%) once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of placebo.
干预措施: Placebo (Drug)
Placebo
Intravenous administration of normal saline (0.9%) once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of placebo.
干预措施: Entecavir (Drug)
Placebo
Intravenous administration of normal saline (0.9%) once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of placebo.
干预措施: Tenofovir (Drug)
Placebo
Intravenous administration of normal saline (0.9%) once every 4 weeks for 3 total doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day), taken throughout the study.
Pretreatment with diphenhydramine 50 mg 2 hours (±30 minutes) prior to administration of placebo.
干预措施: diphenhydramine (Drug)
结局指标
主要结局
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 85
时间窗: Baseline, Day 85
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to Adverse Events (AEs)(From time of informed consent through Day 147 ± 3 days)
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Apparent Clearance (CL)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)(Through 48 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of Entecavir or Tenofovir: AUC0-24(Through 24 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of Entecavir or Tenofovir: AUClast(Through 24 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of Entecavir or Tenofovir: Cmax(Through 24 hours post-dosing on Days 1 and 57)
- Pharmacokinetics of Entecavir or Tenofovir: Time of Cmax (Tmax)(Through 24 hours post-dosing on Days 1 and 57)