A Study of JNJ-73763989, JNJ-64300535, and Nucleos(t)Ide Analogs in Virologically Suppressed, Hepatitis B e Antigen (HBeAg)- Negative Participants With Chronic Hepatitis B Virus Infection

Janssen Research & Development, LLC24 enrolled

Overview

The purpose of this study is to evaluate the efficacy of the study intervention based on hepatitis B surface antigen (HBsAg) levels.

JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-64300535 is a DNA vaccine encoding the core protein and the Polymerase (Pol) protein of HBV. The therapeutic vaccine aims at inducing T-cell-specific immunity against HBV antigens in participants with chronic hepatitis B (CHB). Selected nucleos(t)ide analogs (NAs) used in this study are approved treatments of chronic HBV infection. This study is designed to assess efficacy, safety, and tolerability of a 24-week (Day 1 to Week 24) combination treatment with JNJ-73763989 + NA + JNJ-64300535. The study consists of a Screening phase (4 weeks), Treatment period with JNJ-73763989, NA and JNJ-64300535 (187 days), and a follow-up period (FU Week 1 till FO Week 48). Safety will be assessed by adverse events (AEs), clinical safety laboratory assessments, electrocardiograms (ECGs), vital signs and physical examinations. The total duration of the study is up to 88 weeks (including 4 weeks of screening).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis B, Chronic

Interventions

JNJ-73763989DRUG

JNJ-73763989 injection will be administered subcutaneously.

JNJ-64300535BIOLOGICAL

JNJ-64300535 deoxyribonucleic acid (DNA) vaccine injection will be administered intramuscularly.

ETV monohydrateDRUG

ETV monohydrate film-coated tablets will be administered orally.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator * Participants must have a body mass index (BMI; weight in kilograms \[kg\] divided by the square of height in meters) between 19.0 and 32.0 kilograms per meter square (kg/m\^2), extremes included * A woman of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin) at screening and a negative urine pregnancy test on Day 1 before the first dose of study intervention * Participants must have chronic hepatitis B virus (HBV) infection. HBV infection must be documented by serum hepatitis B surface antigen (HBsAg) positivity at screening. In addition, chronicity must be documented by any of the following, at least 6 months prior to screening: serum HBsAg positivity, hepatitis B e antigen (HBeAg) positivity or HBV deoxyribonucleic acid (DNA) positivity, alanine aminotransferase (ALT) elevation above upper limit of normal (ULN) without another cause than HBV infection, documented transmission event. If none of the above are available, the following ways of documenting chronicity are acceptable at the time of screening: liver biopsy with changes consistent with chronic HBV, or absence of marker for acute HBV infection such as positive immunoglobulin M (IgM) anti- hepatitis B surface protein (HBs) and anti- hepatitis B core protein (HBc) antibodies. Virologically suppressed participants should: a) be HBeAg-negative and anti- hepatitis B e (HBe) positive, b) be on stable HBV treatment, defined as currently receiving nucleos(t)ide analog (NA) treatment for at least 6 months prior to screening and having been on the same NA treatment regimen (at the same dose) as used in this study for at least 3 months at the time of screening, c) have serum HBV deoxyribonucleic acid (DNA) less than (\<) 60 International units per milliliter (IU/mL) on 2 sequential measurements at least 6 months apart (one of which is at screening), and d) have documented ALT values \<2.0\* ULN on 2 sequential measurements at least 6 months apart (one of which is at screening) * Participants must have: a) Fibroscan liver stiffness measurement less than or equal to (\<=) 9.0 kPa within 6 months prior to screening or at the time of screening, or b) If a Fibroscan result is not available: a liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening Exclusion Criteria: * History or evidence of clinical signs or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices * Participants with a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which are considered cured with minimal risk of recurrence) * Participants with any history of or current clinically significant skin disease requiring regular or periodic treatment * Participants with clinically relevant alcohol or drug abuse within 12 months of screening * Participants who had major surgery (example, requiring general anesthesia), excluding diagnostic surgery, within 12 weeks before screening; or will not have fully recovered from surgery; or have surgery planned during the time of expected participation in the study

Locations (13)

UZ Antwerpen

Edegem, Belgium

UZA-SGS

Edegem, Belgium

Hopital Beaujon

Clichy, France

Outcomes

Primary Outcomes

Percentage of Participants with a Reduction of at Least 2 log10 International Units per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline to Week 36

Percentage of participants with a reduction of at least 2 log10 IU/mL in HBsAg levels from baseline to Week 36 will be reported.

Time frame: Baseline to Week 36 (end of study intervention)

Secondary Outcomes

Percentage of Participants with at Least 3-fold Increase in Hepatitis B Virus (HBV)- Specific T-Cell Response Against Vaccine Antigen HBV Core and/or Pol

Percentage of participants with at least 3-fold increase in HBV-specific T-cell response against vaccine antigen HBV core and/or pol as assessed by enzyme-linked immunospot (ELISpot) will be reported.

Time frame: From Day 103 up to Week 84

Percentage of Responders Against Vaccine Antigen HBV Core and/or Pol

Percentage of responders against vaccine antigen HBV core and/or Pol as assessed by ELISpot will be reported. A responder is defined as a participant with at least a 3-fold increase in HBV-specific T-cell response from the start of vaccination against the vaccine antigen core and/or pol, at least at the last timepoint during the vaccination period.

Time frame: Week 28

Percentage of Participants with Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Time frame: Up to Week 84

Percentage of Participants with Serious AEs

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.

Data from ClinicalTrials.gov

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