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

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ClinicalTrials.gov Identifier: NCT03361956
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : December 28, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

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.

Condition or disease Intervention/treatment Phase
Hepatitis B Drug: JNJ-56136379 Drug: Placebo Drug: NA (ETV or TDF) Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 13, 2018
Estimated Primary Completion Date : October 18, 2019
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: Arm 1 (JNJ-56136379) (open label)
Participants with hepatitis B virus (HBV) currently not being treated will receive JNJ-56136379 tablet orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

Placebo Comparator: Part A: Arm 2 (Placebo+NA [ETV] or [TDF])
Participants with HBV currently not being treated will receive matching placebo along with nucleos(t)ide analog (NA) (entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: Placebo
Participants will receive matching placebo tablet orally.

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

Experimental: Part A: Arm 3 (JNJ-56136379 + NA [ETV or TDF])
Participants with HBV currently not being treated will receive JNJ-56136379 along with NA (ETV or TDF) tablet orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

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

Placebo Comparator: Part A: Arm 4 (Placebo + NA [ETV or TDF])
Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: Placebo
Participants will receive matching placebo tablet orally.

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

Experimental: Part A: Arm 5 (JNJ-56136379 + NA [ETV or TDF])
Virologically suppressed participants will receive JNJ-56136379 along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

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

Experimental: Part B: Arm 6 (JNJ-56136379) (open label)
Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose, orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

Placebo Comparator: Part B: Arm 7 (placebo + NA [ETV or TDF])
Participants with HBV currently not being treated will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: Placebo
Participants will receive matching placebo tablet orally.

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

Experimental: Part B: Arm 8 (JNJ-56136379 + NA [ETV or TDF])
Participants with HBV currently not being treated will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

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

Placebo Comparator: Part B: Arm 9 (placebo + NA [ETV or TDF])
Virologically suppressed participants will receive matching placebo along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: Placebo
Participants will receive matching placebo tablet orally.

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

Experimental: Part B: Arm 10 (JNJ-56136379 + NA [ETV or TDF])
Virologically suppressed participants will receive JNJ-56136379 tablet at a high dose along with NA (ETV or TDF) tablets orally for 24 weeks. The eligible participants may enter the extension phase and will continue study drugs up to 48 weeks.
Drug: JNJ-56136379
Participants will receive JNJ-56136379 tablet orally.
Other Name: JNJ-6379

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




Primary Outcome Measures :
  1. Main Study: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24 [ Time Frame: Baseline and Week 24 ]
    Change from baseline in Hepatitis B surface antigen (HBsAg) levels at Week 24 will be assessed.


Secondary Outcome Measures :
  1. Main Study: Number of Participants With Adverse Events (AEs) [ Time Frame: Up to Follow Up (maximum up to Week 96) ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

  2. Main Study: Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to Follow Up (maximum up to Week 96) ]
    A serious adverse event (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. Main Study: Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Electrocardiogram (ECG), Clinically Significant Laboratory Findings [ Time Frame: Up to Follow Up (maximum up to Week 96) ]
    Number of participants with abnormalities in vital signs, physical examinations, ECG, clinically significant laboratory findings will be assessed.

  4. Main Study: Change from Baseline in Hepatitis B Surface Antigen (HBsAg) Levels [ Time Frame: Baseline up to follow up (maximum up to Week 96) ]
    Change from baseline in Hepatitis B surface antigen (HBsAg) levels will be assessed.

  5. Main Study: Percentage of Participants With HBsAg Levels Less Than (<) 1,000 or <100 IU/mL [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with HBsAg levels less than (<) 1,000 or <100 International Units Per Milliliter (IU/mL) will be assessed.

  6. Main Study: Percentage of Participants With Greater Than (>) 0.5 or >1 log10 IU/mL Reduction in HBsAg From Baseline [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with >0.5 or >1 log10 IU/mL reduction in HBsAg from baseline will be assessed.

  7. Main Study: Change From Baseline in Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) Levels [ Time Frame: Baseline up to follow up (maximum up to Week 96) ]
    Change from baseline in Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels will be assessed.

  8. Main Study: Percentage of Participants With Undetectable HBV DNA Levels [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with undetectable HBV DNA levels will be evaluated.

  9. Main Study: Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels [ Time Frame: Baseline up to follow up (maximum up to Week 96) ]
    Change from baseline in Hepatitis B E antigen (HBeAg) levels will be assessed.

  10. Main Study: Percentage of Participants by HBeAg Levels [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants by HBeAg levels will be evaluated.

  11. Main Study: Percentage of Participants With HBsAg or HBeAg Seroclearance [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with seroclearance (defined as HBsAg or HBeAg negativity, respectively) will be assessed.

  12. Main Study: Percentage of Participants With HBsAg or HBeAg Seroconversion [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with seroconversion (defined as HBsAg or HBeAg negativity and anti-HBs or anti-HBe antibody positivity, respectively) will be assessed.

  13. Main Study: Percentage of Participants With Normalized Alanine Aminotransferase (ALT) Levels [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Percentage of participants with normalized alanine aminotransferase (ALT) levels will be assessed whose ALT levers above upper limit of normal at baseline.

  14. Main Study: Percentage of Participants With Virological Breakthrough [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, and 24 ]
    Percentage of participants with viral breakthrough defined as confirmed on treatment HBV DNA increase by greater than (>) 1 log10 from nadir level or confirmed on treatment level >200 International Units Per Milliliter (IU/mL) in participants who had HBV DNA level below the lower limit of quantification (LLOQ) of the HBV DNA assay.

  15. Main Study: Plasma Concentrations of NA (Entecavir [ETV] or Tenofovir Disoproxil Fumarate [TDF]) [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 20, 24, 26 and 28 ]
    Plasma concentrations of NA (entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) administered as monotherapy or co-administered with JNJ-56136379, will be determined.

  16. Main Study: Plasma Concentrations of JnJ-56136379 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 20, 24, 26 and 28 ]
    Plasma concentrations of JNJ-56136379 administered as monotherapy or when co-administered with NA (ETV or TDF), will be determined.

  17. Main Study: Percentage of Participants With Treatment-Associated Mutations [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 26, 28, 36 and 48 ]
    Viral genome sequence analysis will be performed to evaluate emergence of mutations associated with JNJ-56136379 and/or ETV or TDF treatment.


Other Outcome Measures:
  1. Substudy: Change from Baseline in Intrahepatic Hepatitis B Virus (HBV) Covalently Closed Circular Deoxyribo Nucleic Acid (cccDNA) Levels at Week 24 and 48 [ Time Frame: Baseline, Week 24 and Week 48 ]
    Change from baseline in intrahepatic HBV cccDNA levels at Week 24 and 48 will be assessed.

  2. Substudy: Change from Baseline in HBV cccDNA Transcriptional Activity at Week 24 and 48 [ Time Frame: Baseline, Week 24 and Week 48 ]
    Change from baseline in HBV cccDNA transcriptional activity at Week 24 and 48 will be assessed. cccDNA and intracellular viral RNA levels will be used to estimate transcriptional activity of cccDNA.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03361956


Contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

  Show 84 Study Locations
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC

Additional Information:
Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT03361956     History of Changes
Other Study ID Numbers: CR108410
2017-001110-29 ( EudraCT Number )
56136379HPB2001 ( Other Identifier: Janssen Sciences Ireland UC )
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: December 28, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections