activity of nco-48 fumarate in treatment-naive adults with chronic hepatitis b

Conditions: Chronic Hepatitis B

Summary: this is an open-label study evaluating multiple doses of nco-48 fumarate versus tenofovir alafenamide (taf).

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.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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