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

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

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: NCO-48 Fumarate 4 mg; Drug: NCO-48 Fumarate 20 mg; Drug: Tenofovir Alafenamide 25 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Monterey Park, California, United States, 91754
      • National Institute of Clinical Research, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: NCO-48 Fumarate 4 mg; 2 x 2mg NCO-48 Fumarate over 28 days of therapy
Experimental: 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.	Drug: NCO-48 Fumarate 20 mg; 2 x 10 mg NCO-48 Fumarate over 28 days of therapy
Active Comparator: 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.	Drug: Tenofovir Alafenamide 25 mg; 25 mg over 28 days of therapy; Other Names: Vemlidy ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hepatitis B virus (HBV) DNA	Time-weighted average change from baseline through Week 4 in plasma HBV DNA (log10 IU/mL) for NCO-48 Fumarate 4 and 20-mg.	Up to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HBV DNA for tenofovir alafenamide (TAF)	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.	Up to Week 4
Incidence of Treatment-Emergent Adverse Events	Safety and tolerability is measured by the incidence of treatment-emergent adverse events.	Up to week 4
NCO-48 Fumarate Area Under the Concentration -Time Curve (AUC)	Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate AUC.	Up to week 4
NCO-48 Fumarate Maximum Plasma Concentration (Cmax)	Blood samples are to be collected at designated time points for the determination of the NCO-48 Fumarate Cmax.	Up to week 4
Tenofovir (TFV) Area under the Concentration-Time Curve (AUC)	Blood samples are to be collected at designated time points for the determination of TFV AUC.	Up to week 4
TFV Maximum Plasma Concentration (Cmax)	Blood samples are to be collected at designated time points for the determination of TFV Cmax.	Up to week 4

Collaborators and Investigators

• Sponsor: Nucorion Pharmaceuticals, Inc.
• Collaborators: Ligand Pharmaceuticals
• Investigators: Study Director: Keith Marschke, Ligand Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): December 28, 2022

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: NCO48F-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No