Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Birinapant in Subjects With Chronic Hepatitis B
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 7
- 试验地点
- 3
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This study evaluates the addition of birinapant in subjects with chronic Hepatitis B who are currently receiving anti-viral therapy with either tenofovir or entecavir. Patients will receive either birinapant or placebo in addition to their anti-viral therapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented history of chronic Hepatitis B infection currently being treated with tenofovir or entecavir for at least 3 months
- •Measurable titer of HBsAg
- •HBV DNA level < 2 log copies/mL or 10² copies/mL
- •No more than Child-Pugh score of 5 plus a valid FibroScan® of at least 10 readings with a median score of <7 and interquartile range of < 30%
- •Adequate liver function, aspartate AST and ALT ≤2 x ULN
- •Adequate renal function as evidenced by creatinine ≤2 mg/dL
排除标准
- •Participation in any interventional study within 4 weeks prior to Screening
- •Known HIV infection, Hepatitis C, or other significant hepatic disorder including cirrhosis (Child-Pugh Class B or C)
- •Serious illness or autoimmune disease or other known liver disease
- •Uncontrolled hypertension
- •Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications, or clinically significant cardiac disease
- •Currently breast feeding, pregnant or planning on becoming pregnant
- •Known allergy or hypersensitivity to any of the formulation components of birinapant or placebo, including citric acid
- •History of cranial nerve palsy
- •Current treatment with anti-TNF therapies or has received treatment with anti-TNF therapies within the last 6 months
- •Use of non-steroidal anti-inflammatory drugs
研究组 & 干预措施
Antiviral Therapy & Birinapant
Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and birinapant administered as a 30 minute IV infusion once weekly for four weeks.
干预措施: Antiviral Therapy (tenofovir or entecavir) (Drug)
Antiviral Therapy & Birinapant
Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and birinapant administered as a 30 minute IV infusion once weekly for four weeks.
干预措施: Birinapant (Drug)
Antiviral Therapy & Placebo
Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and placebo (for birinapant) administered as a 30 minute infusion once weekly for four weeks.
干预措施: Antiviral Therapy (tenofovir or entecavir) (Drug)
Antiviral Therapy & Placebo
Antiviral therapy (tenofovir 300 mg or entecavir 0.5 mg) taken once daily by mouth, and placebo (for birinapant) administered as a 30 minute infusion once weekly for four weeks.
干预措施: Placebo (for birinapant) (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: From Screening through end of study, up to 13 weeks
次要结局
- Pharmacokinetics of birinapant (in plasma): maximum concentration (Cmax), time of maximum concentration (Tmax), area under the curve (AUC) extrapolated to time infinity, AUC from dosing to last quantifiable concentration(Day -1 through Day 26)
- Pharmacokinetics of oral antiviral medication (tenofovir or entecavir): Cmax, Tmax, AUC from dosing to last quantifiable concentration, t1/2, CL, terminal disposition rate constant, Vdss(Day -1, Day 1 and Day 22)
- Pharmacokinetics of birinapant (in plasma): terminal elimination half-life (t1/2), clearance (CL), terminal disposition rate constant,volume of distribution (Vdss)(Day -1 through Day 26)
- Hepatitis B markers (Determine levels of HBsAg, HBeAg, HBV DNA, and HBsAb)(Screening through Day 29)
- Pharmacodynamic effect of birinapant on cIAP1 and cIAP2 levels in peripheral blood mononuclear cells (PBMC) and levels of cluster of differentiation 4 and 8 (CD4+, CD+8) lymphocytes(Screening through Day 29)