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

Sponsor

Nucorion Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04629976

Collaborator

Ligand Pharmaceuticals (Industry)

Enrollment

Location

Arms

22.6

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: NCO-48 Fumarate 4 mg Drug: NCO-48 Fumarate 20 mg Drug: Tenofovir Alafenamide 25 mg	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

After Screening procedures, eligible subjects will be randomized 1:1:1 to receive either open-label NCO-48 Fumarate 4 mg (2 x 2 mg) or 20 mg (2 x 10 mg), or open-label TAF 25 mg for 28 days.After Screening procedures, eligible subjects will be randomized 1:1:1 to receive either open-label NCO-48 Fumarate 4 mg (2 x 2 mg) or 20 mg (2 x 10 mg), or open-label TAF 25 mg for 28 days.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 12, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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 ®

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 ®

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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