Activity of NCO-48 Fumarate in Treatment-Naive Adults With Chronic Hepatitis B
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT04629976
- Lead Sponsor
- Nucorion Pharmaceuticals, Inc.
- Brief Summary
This is an open-label study evaluating multiple doses of NCO-48 Fumarate versus tenofovir alafenamide (TAF).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tenofovir alafenamide 25 mg 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. NCO-48 Fumarate 4 mg 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. NCO-48 Fumarate 20 mg 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.
- Primary Outcome Measures
Name Time Method Change in hepatitis B virus (HBV) DNA 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.
- Secondary Outcome Measures
Name Time Method Tenofovir (TFV) Area under the Concentration-Time Curve (AUC) Up to week 4 Blood samples are to be collected at designated time points for the determination of TFV AUC.
NCO-48 Fumarate Area Under the Concentration -Time Curve (AUC) Up to week 4 Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate AUC.
NCO-48 Fumarate Maximum Plasma Concentration (Cmax) Up to week 4 Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate Cmax.
Change in HBV DNA for tenofovir alafenamide (TAF) Up to Week 4 Comparing the short-term antiviral activity of NCO-48 Fumarate with TAF 25 mg. This is measured by time-weighted average change from baseline through Week 4 in plasma HBV DNA (log10 IU/mL) for TAF.
Incidence of Treatment-Emergent Adverse Events Up to week 4 Safety and tolerability is measured by the incidence of treatment-emergent adverse events.
TFV Maximum Plasma Concentration (Cmax) Up to week 4 Blood samples are to be collected at designated time points for the determination of TFV Cmax.
Trial Locations
- Locations (1)
National Institute of Clinical Research, Inc
🇺🇸Monterey Park, California, United States