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

NCT ID: NCT05123599

Last Updated: 2025-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-06
• Study Completion Date: 2024-06-26

Brief Summary

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

Detailed Description

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).

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)

Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate \[ETV\], Tenofovir disoproxil or Tenofovir alafemide \[TAF\]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 injection will be administered subcutaneously.

JNJ-64300535

Intervention Type: BIOLOGICAL

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

ETV monohydrate

Intervention Type: DRUG

ETV monohydrate film-coated tablets will be administered orally.

Tenofovir disoproxil

Intervention Type: DRUG

Tenofovir disoproxil film-coated tablets will be administered orally.

TAF

Intervention Type: DRUG

TAF film-coated tablets will be administered orally.

Interventions

JNJ-73763989

JNJ-73763989 injection will be administered subcutaneously.

Intervention Type: DRUG

JNJ-64300535

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

Intervention Type: BIOLOGICAL

ETV monohydrate

ETV monohydrate film-coated tablets will be administered orally.

Intervention Type: DRUG

Tenofovir disoproxil

Tenofovir disoproxil film-coated tablets will be administered orally.

Intervention Type: DRUG

TAF

TAF film-coated tablets will be administered orally.

Intervention Type: DRUG

Other Intervention Names

JNJ-3989; JNJ-0535

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

UZ Antwerpen

Edegem, , Belgium

UZA-SGS

Edegem, , Belgium

Hopital Beaujon

Clichy, , France

Hopital de La Croix Rousse

Lyon, , France

Irccs Ospedale Maggiore Di Milano

Milan, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

New Zealand Clinical Research

Auckland, , New Zealand

ID Clinic

Mysłowice, , Poland

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

E-DA Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, , Taiwan

Kings College Hospital

London, , United Kingdom

Countries

Belgium; France; Italy; New Zealand; Poland; Spain; Taiwan; United Kingdom

Other Identifiers

2020-005584-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

73763989PAHPB1006

Identifier Type: OTHER

Identifier Source: secondary_id

CR109042

Identifier Type: -

Identifier Source: org_study_id