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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04629976
• Other study ID #: NCO48F-02
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2021
• Est. completion date: December 28, 2022

Study information

• Verified date: January 2023
• Source: Nucorion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 28, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• NCO-48 Fumarate 4 mg
2 x 2mg NCO-48 Fumarate over 28 days of therapy
• NCO-48 Fumarate 20 mg
2 x 10 mg NCO-48 Fumarate over 28 days of therapy
• Tenofovir Alafenamide 25 mg
25 mg over 28 days of therapy

Locations

Country	Name	City	State
United States	National Institute of Clinical Research, Inc	Monterey Park	California

Sponsors (2)

Lead Sponsor	Collaborator
Nucorion Pharmaceuticals, Inc.	Ligand Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Incidence of Treatment-Emergent Adverse Events	Safety and tolerability is measured by the incidence of treatment-emergent adverse events.	Up to week 4
Secondary	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
Secondary	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
Secondary	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
Secondary	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