Randomized, Open-Label, Active Comparator, Multiple Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-Hepatitis B Virus (HBV) Activity of NCO-48 Fumarate in Treatment-Naive Adults With Chronic HBV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Change in hepatitis B virus (HBV) DNA
研究概览
简要总结
This is an open-label study evaluating multiple doses of NCO-48 Fumarate versus tenofovir alafenamide (TAF).
详细描述
This is a randomized, open-label, active comparator, multiple oral dose study to evaluate the safety, tolerability, pharmacokinetics, and anti-hepatitis B virus (HBV) activity of NCO-48 Fumarate in treatment-naive adults with chronic HBV infection. This study will evaluate the safety, viral kinetics, and antiviral activity of 2 different doses of NCO-48 Fumarate over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of NCO-48 Fumarate versus 25 mg tenofovir alafenamide (TAF) over 28 days of 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
- None
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
- •Adult male and female subjects between 18 and 65 years of age
- •Female subjects of non-childbearing potential must be surgically sterile or postmenopausal at the Screening Visit
- •Female subjects of childbearing potential who are sexually active with a non-sterile male partner must be using a medically acceptable form of birth control for the duration of the study and for 30 days after the last dose of study drug and must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test upon admission to the study site
- •HBV treatment-naive or treatment-experienced with (pegylated or non pegylated) interferon alpha (must have ended at least 6 months prior to the Screening Visit)
- •Screening plasma HBV DNA ≥ 2x10^3 IU/mL
- •Positive for serum hepatitis B surface antigen for more than 6 months
- •Estimated creatinine clearance (CLCr) ≥ 70 mL/min
- •Serum transaminase activity (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] levels) <10 x the upper limit of normal
- •Compensated liver disease with normal prothrombin time/international normalized ratio, hematology, albumin, bilirubin (unless subject has Gilbert's disease). Serum AST and/or ALT levels may be normal or elevated
- •Body mass index within the range of 18.5 to 35 kg/m2, inclusive, and body weight >45 kg
- •Normal vital signs, without any clinically significant abnormalities at the Screening Visit
- •Subjects who have normal or abnormal clinically insignificant clinical laboratory assessments as considered by the Investigator from pre-treatment blood tests to assess hematology, liver (except for serum AST and/or ALT levels) and renal biochemistry, urinalysis, and drug screen
- •Normal 12-lead electrocardiogram (ECG), with no clinically significant abnormalities of rate, rhythm, or conduction and including normal heart rate-corrected QT interval segment time at the Screening Visit
排除标准
- •Received treatment with TFV disoproxil fumarate or TAF (including clinical study experience)
- •Positive for hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
- •History or presence of asthma or other pulmonary disease, thyroid disease, or other liver disease
- •Hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of study drug, or would place the subject at increased risk
- •Abnormal laboratory values that are considered clinically significant
- •Have used medication, other than topical products without significant systemic absorption, hormonal contraceptives, or hormone replacement therapy and thyroid medication for at least 6 months
- •Unwilling to refrain from consumption of alcohol within 48 hours prior to each dose of study drug and during the inpatient period, or have a history of significant alcohol abuse within 1 year prior to Screening
- •Positive urine drug screen, or positive alcohol breath test at Screening or upon admission to the study site
- •Use of illicit drugs within 3 months prior to the Screening Visit or hard drugs within 1 year prior to the Screening Visit, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction
- •Women who are breastfeeding or have a positive pregnancy test at the Screening Visit or at any time during the study
研究组 & 干预措施
NCO-48 Fumarate 4 mg
Eligible subjects will be randomized 1:1:1 to receive either open-label NCO-48 Fumarate 4 mg or 20 mg, or open-label TAF 25 mg for 28 days.
干预措施: NCO-48 Fumarate 4 mg (Drug)
NCO-48 Fumarate 20 mg
Eligible subjects will be randomized 1:1:1 to receive either open-label NCO-48 Fumarate 4 mg or 20 mg, or open-label TAF 25 mg for 28 days.
干预措施: NCO-48 Fumarate 20 mg (Drug)
Tenofovir alafenamide 25 mg
Eligible subjects will be randomized 1:1:1 to receive either open-label NCO-48 Fumarate 4 mg or 20 mg, or open-label TAF 25 mg for 28 days.
干预措施: Tenofovir Alafenamide 25 mg (Drug)
结局指标
主要结局
Change in hepatitis B virus (HBV) DNA
时间窗: Up to Week 4
Time-weighted average change from baseline through Week 4 in plasma HBV DNA (log10 IU/mL) for NCO-48 Fumarate 4 and 20-mg.
次要结局
- Tenofovir (TFV) Area under the Concentration-Time Curve (AUC)(Up to week 4)
- NCO-48 Fumarate Area Under the Concentration -Time Curve (AUC)(Up to week 4)
- NCO-48 Fumarate Maximum Plasma Concentration (Cmax)(Up to week 4)
- Incidence of Treatment-Emergent Adverse Events(Up to week 4)
- Change in HBV DNA for tenofovir alafenamide (TAF)(Up to Week 4)
- TFV Maximum Plasma Concentration (Cmax)(Up to week 4)