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

• Register: ClinicalTrials.gov
• Last refreshed on: 7 September 2021
• Main ID: NCT03361956
• Date of registration: 29/11/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen Sciences Ireland UC
• Public title: An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection
• Scientific 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
• Date of first enrolment: February 13, 2018
• Target sample size: 232
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03361956
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belgium, Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Janssen Sciences Ireland UC Clinical Trial
• Affiliation: Janssen Sciences Ireland UC

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hepatitis B

Intervention(s)

Drug: JNJ-56136379

Drug: NA (ETV or TDF)

Drug: Placebo

Primary Outcome(s)

Main Study: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels at Week 24 [Time Frame: Baseline and Week 24]

Secondary Outcome(s)

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)]

Main Study: Number of Participants With Serious Adverse Events (SAEs) [Time Frame: Up to Follow Up (maximum up to Week 96)]

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]

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]

Main Study: Change From Baseline in Hepatitis B E Antigen (HBeAg) Levels [Time Frame: Baseline up to follow up (maximum up to Week 96)]

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]

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]

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]

Main Study: Percentage of Participants With Virological Breakthrough [Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, and 24]

Main Study: Plasma Concentrations of NA (Entecavir [ETV] or Tenofovir Disoproxil Fumarate [TDF]) [Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26 and 28]

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]

Main Study: Plasma Concentrations of JnJ-56136379 [Time Frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 26 and 28]

Main Study: Change from Baseline in Hepatitis B Surface Antigen (HBsAg) Levels [Time Frame: Baseline up to follow up (maximum up to Week 96)]

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)]

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]

Main Study: Number of Participants With Adverse Events (AEs) [Time Frame: Up to Follow Up (maximum up to Week 96)]

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]

Secondary ID(s)

2017-001110-29

56136379HPB2001

CR108410

Source(s) of Monetary Support

Please refer to primary and secondary sponsors