Activity of NCO-48 Fumarate in Treatment-Naive Adults With Chronic Hepatitis B

Nucorion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Chronic Hepatitis B

Treatments: Drug: Tenofovir Alafenamide 25 mg; Drug: NCO-48 Fumarate 4 mg; Drug: NCO-48 Fumarate 20 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04629976

NCO48F-02

Details and patient eligibility

About

This is an open-label study evaluating multiple doses of NCO-48 Fumarate versus tenofovir alafenamide (TAF).

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 3 patient groups

NCO-48 Fumarate 4 mg

Experimental group

Description:

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.

Treatment:

Drug: NCO-48 Fumarate 4 mg

NCO-48 Fumarate 20 mg

Experimental group

Description:

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.

Treatment:

Drug: NCO-48 Fumarate 20 mg

Tenofovir alafenamide 25 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Tenofovir Alafenamide 25 mg