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

NCT ID: NCT04629976

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-12
• Study Completion Date: 2022-12-28

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

NCO-48 Fumarate 4 mg

Intervention Type: DRUG

2 x 2mg NCO-48 Fumarate over 28 days of therapy

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.

Group Type: EXPERIMENTAL

NCO-48 Fumarate 20 mg

Intervention Type: DRUG

2 x 10 mg NCO-48 Fumarate over 28 days of therapy

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.

Group Type: ACTIVE_COMPARATOR

Tenofovir Alafenamide 25 mg

Intervention Type: DRUG

25 mg over 28 days of therapy

Interventions

NCO-48 Fumarate 4 mg

2 x 2mg NCO-48 Fumarate over 28 days of therapy

Intervention Type: DRUG

NCO-48 Fumarate 20 mg

2 x 10 mg NCO-48 Fumarate over 28 days of therapy

Intervention Type: DRUG

Tenofovir Alafenamide 25 mg

25 mg over 28 days of therapy

Intervention Type: DRUG

Other Intervention Names

Vemlidy ®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ligand Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Nucorion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keith Marschke

Role: STUDY_DIRECTOR

Ligand Pharmaceuticals

Locations

National Institute of Clinical Research, Inc

Monterey Park, California, United States

Countries

United States

Other Identifiers

NCO48F-02

Identifier Type: -

Identifier Source: org_study_id