A Phase 2a, Randomized, Partially-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Pharmacokinetics of Treatment With Multiple Doses of JNJ-56136379 as Monotherapy and in Combination With a Nucleos(t)Ide Analog in Subjects With Chronic Hepatitis B Virus Infection

Janssen Sciences Ireland UC76 sites in 13 countries232 target enrollmentFebruary 13, 2018

ConditionsHepatitis B

InterventionsJNJ-56136379 NA (ETV or TDF)Placebo

DrugsJNJ-56136379 Placebo NA (ETV or TDF)

Overview

Phase: Phase 2
Intervention: JNJ-56136379
Conditions: Hepatitis B
Sponsor: Janssen Sciences Ireland UC
Enrollment: 232
Locations: 76
Primary Endpoint: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The main purpose of this study is to evaluate efficacy of 24 weeks of study treatment, in terms of changes in hepatitis B surface antigen (HBsAg) levels.

Detailed Description

The main study consists of 2-parts and each part will consist of 2 types of Chronic Hepatitis B-infected participant populations. Each part of the study will consist of screening phase (up to 8 weeks), treatment phase (24 weeks or 48 weeks, depending on treatment response), and post-treatment follow-up phase (24 weeks or 48 weeks, depending on treatment response). The duration of individual participation will be up to approximately 56 weeks (participants not eligible to continue treatment in extension phase), up to 80 weeks (participants continuing treatment in extension phase but not meeting treatment completion criteria), or up to 104 weeks (participants meeting treatment completion criteria). The safety and efficacy will be monitored throughout the study. In a separate substudy, at selected clinical sites, percutaneous core liver biopsy will be performed to evaluate changes of intrahepatic viral parameters.

Registry

clinicaltrials.gov

Start Date

February 13, 2018

End Date

August 13, 2020

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Janssen Sciences Ireland UC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants must have a body mass index (weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 35.0 kilogram / square meter (kg/m\^2), extremes included
•Participants must have chronic hepatitis B virus infection (CHB) infection documented by: Serum hepatitis B surface antigen (HBsAg)-positive at screening and serum HBsAg- or hepatitis B virus (HBV) deoxyribonucleic acid (DNA)-positive at least 6 months prior to screening; Serum immunoglobulin M (IgM) anti- hepatitis B core-related (HBc) antibody negative at screening
•In participants currently not being treated (Treatment Arms 1-2-3 and 6-7-8): Participants must not be receiving any CHB treatment at screening, that is, Have never received treatment with HBV antiviral medicines, including NAs or interferon (IFN) products, OR Have not been on treatment with HBV antiviral medicines, including nucleos(t)ide analog (NA)s or IFN products within 6 months prior to baseline (first intake of study drugs), and participants must be HBeAg-positive and have HBV DNA greater than or equal to (\>=) 20,000 International Units Per Milliliter (IU/mL), OR be hepatitis B e antigen (HBeAg)-negative and have HBV DNA \>=2,000 IU /mL at screening, and participants must have HBsAg greater than (\>) 250 IU/mL at screening, and participants must have alanine aminotransferase (ALT) \> upper limit of normal (ULN) and less than or equal to (\<=) 5 \* ULN at screening, determined in the central laboratory
•In virologically suppressed participants (Treatment Arms 4-5 and 9-10): Participants must be virologically suppressed by current NA treatment (entecavir (ETV) or tenofovir disoproxil fumarate (TDF)) as defined by HBV DNA less than (\<) 60 IU/mL at screening and at least 6 months prior to screening, and participants must be on the same NA treatment (ETV or TDF) and the same dose for \>=12 months prior to screening, and participants must have HBsAg \> 250 IU/mL at screening, and participants must have ALT \<=2\*ULN at screening
•Participants must have: A liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening or at the time of screening, OR FibroScan liver stiffness measurement \<8.0 kilopascal (kPa) within 6 months prior to screening or at the time of screening

Exclusion Criteria

•Main Study:
•Participants who test positive for anti-hepatitis B surface (HBs) antibodies
•Participants with current hepatitis A virus infection (confirmed by hepatitis A antibody immunoglobulin M \[IgM\]), hepatitis D virus (HDV) infection (confirmed by HDV antibody), hepatitis E virus infection (confirmed by hepatitis E antibody IgM), or human immunodeficiency virus (HIV)-1 or HIV-2 infection (confirmed by antibodies) at screening; participants with a history of or current HCV infection (confirmed by HCV antibody). Evidence of other active infection (bacterial, viral, fungal, including acute tuberculosis) deemed clinically relevant by the investigator that would interfere with study conduct or its interpretation will also lead to exclusion
•Participants with any evidence of hepatic decompensation at any time point prior to or at the time of screening: Direct bilirubin \>1.2\* ULN, or International normalized ratio (INR) \>1.5\* ULN, or Serum albumin \< lower limit of normal (LLN), or documented history or current evidence of variceal bleeding, ascites, or hepatic encephalopathy
•Participants with a history of cardiac arrhythmia (example, extrasystoli, tachycardia at rest), history of risk factors for Torsades de Pointes syndrome (example, hypokalemia, family history of long QT syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant 12 lead electrocardiograms (ECGs) abnormalities), moderate to severe valvular disease, or uncontrolled hypertension at screening
•Participants with contraindications to the use of ETV or TDF per local prescribing information
•Presence of coagulopathy or hemoglobinopathy (including sickle cell disease, thalassemia)
•Use of any anti-coagulant, anti-platelet, or non-steroidal anti-inflammatory drug medications from 10 days before until 5 days after each liver biopsy
•Presence of ascites, focal liver lesions, and other findings that would be contraindications for liver biopsies

Arms & Interventions

Part A: Arm 1 (JNJ-56136379 or NA) (open label)

Participants with hepatitis B virus (HBV) currently not being treated and receiving JNJ-56136379 tablet (at a lower dose) orally for 24 weeks, will stop further dosing with JNJ-56136379 and start treatment with nucleos(t)ide analog (NA) (entecavir \[ETV\] or tenofovir disoproxil fumarate \[TDF\]), and enter the 24 week post treatment follow-up phase.

Intervention: JNJ-56136379