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

NCT04629976 | Completed Phase 1 FDA Drug

• 1 other identifier: NCO48F-02
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in HBV DNA for tenofovir alafenamide (TAF)

  Up to Week 4

• Incidence of Treatment-Emergent Adverse Events

  Up to week 4

• NCO-48 Fumarate Area Under the Concentration -Time Curve (AUC)

  Up to week 4

• NCO-48 Fumarate Maximum Plasma Concentration (Cmax)

  Up to week 4

• Tenofovir (TFV) Area under the Concentration-Time Curve (AUC)

  Up to week 4

Study Arms (3)

NCO-48 Fumarate 4 mg

EXPERIMENTAL

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

NCO-48 Fumarate 20 mg

EXPERIMENTAL

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

Tenofovir alafenamide 25 mg

ACTIVE COMPARATOR

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

Interventions

NCO-48 Fumarate 4 mg DRUG

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

NCO-48 Fumarate 4 mg

NCO-48 Fumarate 20 mg DRUG

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

NCO-48 Fumarate 20 mg

Tenofovir Alafenamide 25 mg DRUG

25 mg over 28 days of therapy

Also known as: Vemlidy ®

Tenofovir alafenamide 25 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nucorion Pharmaceuticals, Inc.: lead
• Ligand Pharmaceuticals: collaborator

Study Sites (1)

National Institute of Clinical Research, Inc

Monterey Park, California, 91754, United States

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Keith Marschke

  Ligand Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 16, 2020
• Study Start: January 12, 2021
• Primary Completion: September 30, 2022
• Study Completion: December 28, 2022
• Last Updated: January 4, 2023

Record last verified: 2023-01

Locations

US (1)