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Completed

NCT Number: NCT03361956

An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection

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.

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Key information

Conditions

Hepatitis B Blood-Borne Infections Communicable Diseases DNA Virus Infections Digestive System Diseases Hepadnaviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases Virus Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg), Antwerp, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Substudy:

  • 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

Treatment and study plan

JNJ-56136379

Drug

Participants will receive JNJ-56136379 tablet orally.

Other names: JNJ-6379

Placebo

Drug

Participants will receive matching placebo tablet orally.

NA (ETV or TDF)

Drug

Participants will receive NA (ETV or TDF) tablet orally as per approved label.

Primary outcomes

  1. Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels in Currently Not Treated Population at Week 24

    Time frame: Baseline and Week 24

    Change from baseline in HBsAg levels in currently not treated population at Week 24 based on Hepatitis B e Antigen (HBeAg) status was reported. Currently not treated population defined as participants who didn't receive any hepatitis B virus (HBV) treatment 6 months prior to baseline.

  2. Change From Baseline in HBsAg Levels in Virologically Suppressed Population at Week 24

    Time frame: Baseline and Week 24

    Change from baseline in HBsAg levels in virologically suppressed population at Week 24 based on HBeAg status was reported. Virologically suppressed population defined as participants who were on entecavir (ETV) or tenofovir disoproxil fumarate (TDF) for at least 12 months prior to screening and had HBV deoxyribonucleic acid (DNA) <60 IU/mL. This outcome measure was planned to be analyzed for specified arms only.

Secondary outcomes

  1. Number of Participants With Treatment- Emergent Adverse Events (AEs)

    Time frame: Up to Week 48

    An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent AEs were AEs with onset during the treatment phase or that worsened since baseline.

  2. Number of Participants With Serious Adverse Events (SAEs)

    Time frame: Up to Week 80

    A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  3. Number of Participants With Clinically Significant Changes in Vital Signs, Physical Examinations, Electrocardiogram (ECG), and Clinical Laboratory Tests

    Time frame: Up to Week 80

    Number of participants with clinically significant changes in vital signs, physical examinations, ECG, and clinical laboratory tests (including hematology, blood biochemistry, blood coagulation, and urinalysis) were reported.

  4. Change From Baseline in HBsAg Levels in Currently Not Treated Population Over Time

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBsAg levels in currently not treated population based on HBeAg status was reported.

  5. Change From Baseline in HBsAg Levels in Virologically Suppressed Population Over Time

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBsAg levels in virologically suppressed population based on HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.

  6. Percentage of Participants With HBsAg Levels Less Than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) in Currently Not Treated Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with HBsAg levels <1,000 or <100 IU/mL in currently not treated population based on their HBeAg status were reported.

  7. Percentage of Participants With HBsAg Levels <1,000 or <100 IU/mL in Virologically Suppressed Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with HBsAg levels <1,000 or <100 IU/mL in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.

  8. Percentage of Participants With Greater Than (>) 0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Currently Not Treated Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with >0.5 log10 IU/mL or >1 log10 IU/mL reduction in HBsAg from baseline in currently not treated population based on their HBeAg status were reported.

  9. Percentage of Participants With >0.5 log10 IU/mL or >1 log10 IU/mL Reduction in HBsAg From Baseline in Virologically Suppressed Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with >0.5 log10 IU/mL or >1 log10 IU/mL reduction in HBsAg from baseline in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.

  10. Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels in Currently Not Treated Population

    Time frame: Baseline up to Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBV DNA levels in currently not treated population based on their HBeAg status was reported.

  11. Change From Baseline in HBV DNA Levels in Virologically Suppressed Population

    Time frame: Baseline up to Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBV DNA levels in virologically supressed population based on their HBeAg status was reported. This outcome measure was planned to be analyzed for specified arms only.

  12. Percentage of Participants With Undetectable HBV DNA Levels in Currently Not Treated Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with undetectable HBV DNA levels in currently not treated population based on their HBeAg status was evaluated.

  13. Percentage of Participants With Undetectable HBV DNA Levels in Virologically Suppressed Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with undetectable HBV DNA levels in virologically suppressed population based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.

  14. Change From Baseline in HBeAg Levels in Currently Not Treated Population

    Time frame: Baseline up to Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBeAg levels in HBeAg positive currently not treated population was reported.

  15. Change From Baseline in HBeAg Levels in Virologically Suppressed Population

    Time frame: Baseline up to Weeks 24, 48 and Follow-up Week 24

    Change from baseline in HBeAg levels in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.

  16. Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Currently Not Treated Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with >0.5 log10 IU/mL and >1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive currently not treated population was reported.

  17. Percentage of Participants With >0.5 log10 IU/mL and >1 log10 IU/mL Reduction in HBeAg From Baseline in Virologically Suppressed Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with >0.5 log10 IU/mL and >1 log10 IU/mL reduction in HBeAg from baseline in HBeAg positive virologically suppressed population was reported. This outcome measure was planned to be analyzed for specified arms only.

  18. Percentage of Participants With HBsAg Seroclearance in Currently Not Treated Population

    Time frame: Weeks 24 and 48

    Percentage of participants with HBsAg seroclearance in currently not treated population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed at specified timepoints only.

  19. Percentage of Participants With HBsAg Seroclearance in Virologically Suppressed Population

    Time frame: Weeks 24 and 48

    Percentage of participants with HBsAg seroclearance in virologically suppressed population based on their HBeAg status were reported. Seroclearance at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at Week 24/48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. This outcome measure was planned to be analyzed for specified arms and specific timepoints only .

  20. Percentage of Participants With HBsAg Seroconversion in Currently Not Treated Population

    Time frame: Weeks 24 and 48

    Percentage of participants with HBsAg seroconversion in currently not treated population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified timepoints only.

  21. Percentage of Participants With HBsAg Seroconversion in Virologically Suppressed Population

    Time frame: Weeks 24 and 48

    Percentage of participants with HBsAg seroconversion in virologically suppressed population based on their HBeAg status were reported. Seroconversion at Week 24/48 of the treatment defined as a confirmed loss of HBsAg at week 24/48 of the treatment and an appearance of Anti-HBs. This outcome measure was planned to be analyzed for specified arms and specified timepoints only.

  22. Percentage of Participants With Normalized Alanine Aminotransferase (ALT) Levels in Currently Not Treated Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with normalized ALT levels in currently not treated population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported.

  23. Percentage of Participants With Normalized ALT Levels in Virologically Suppressed Population

    Time frame: Weeks 24, 48 and Follow-up Week 24

    Percentage of participants with normalized ALT levels in virologically suppressed population, whose ALT levels were above upper limit of normal at baseline based on their HBeAg status were reported. This outcome measure was planned to be analyzed for specified arms only.

  24. Percentage of Participants With Virological Breakthrough in Currently Not Treated Population

    Time frame: Weeks 24 and 48

    Percentage of participants with virological breakthrough in currently not treated population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by >1 log10 from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay.

  25. Percentage of Participants With Virological Breakthrough in Virologically Suppressed Population

    Time frame: Weeks 24 and 48

    Percentage of participants with virological breakthrough in virologically suppressed population based on their HBeAg status was reported. Virological breakthrough defined as confirmed on treatment HBV DNA increase by >1 log10 from nadir level or confirmed on treatment level >200 IU/mL in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay. This outcome measure was planned to be analyzed for specified arms only.

  26. Plasma Concentrations of Entecavir [ETV] in Currently Not Treated Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in currently not treated population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.

  27. Plasma Concentrations of ETV in Virologically Suppressed Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of ETV administered as monotherapy or co-administered with JNJ-56136379 in virologically suppressed population was determined. As planned, plasma concentration of ETV co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.

  28. Plasma Concentrations of Tenofovir Disoproxil Fumarate (TDF) in Currently Not Treated Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.

  29. Plasma Concentrations of TDF in Virologically Suppressed Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of TDF administered as monotherapy or co-administered with JNJ-56136379 was determined. As planned, plasma concentration of TDF co-administered with placebo was analyzed separately for Part A and Part B. Samples were analyzed using POP PK modeling.

  30. Plasma Concentrations of JNJ-56136379 in Currently Not Treated Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of JNJ-56136379 in currently not treated population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.

  31. Plasma Concentrations of JNJ-56136379 in Virologically Suppressed Population

    Time frame: Day 1: 0 hours, 2 hours; Weeks 1, 2, 4, 8, 12, 20, 24, 28, 32, 36, 44, 48: 0 hours; Follow-up: Weeks 2 and 4

    Plasma concentrations of JNJ-56136379 in virologically suppressed population administered as monotherapy or when co-administered with NA (ETV or TDF) was determined. As planned, the plasma concentration of JNJ-56136379 when co-administered with NA was determined separately for each NA treatment (ETV and TDF). Samples were analyzed using POP PK modeling.

  32. Number of Participants With Treatment-Associated Mutations

    Time frame: From Week 0 to Week 24, From Week 25 to Week 48, Up to Follow-up Week 24

    Number of participants with treatment-associated mutations were reported. Viral genome sequence analysis was performed to evaluate emergence of mutations associated with JNJ-56136379 considering 15 HBV core protein positions of interest. This outcome measure was planned to be analyzed for specified arms only.

Sponsors and collaborators

Lead sponsor

Janssen Sciences Ireland UC

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2019
Study completion
2020
First posted
Dec 5, 2017
Registry last updated
Nov 17, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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