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

NCT05123599 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1090422020-005584-3073763989PAHPB1006
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 13

Brief Summary

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

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 36 (end of study intervention)

Secondary Outcomes (24)

• 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

  From Day 103 up to Week 84

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

  Week 28

• Percentage of Participants with Adverse Events (AEs)

  Up to Week 84

• Percentage of Participants with Serious AEs

  Up to Week 84

• Percentage of Participants with Abnormalities in Clinical Laboratory Tests

  Up to Week 84

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: JNJ-73763989; Biological: JNJ-64300535; Drug: ETV monohydrate; Drug: Tenofovir disoproxil; Drug: TAF

Interventions

JNJ-73763989 DRUG

JNJ-73763989 injection will be administered subcutaneously.

Also known as: JNJ-3989

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

JNJ-64300535 BIOLOGICAL

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

Also known as: JNJ-0535

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

ETV monohydrate DRUG

ETV monohydrate film-coated tablets will be administered orally.

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

Tenofovir disoproxil DRUG

Tenofovir disoproxil film-coated tablets will be administered orally.

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

TAF DRUG

TAF film-coated tablets will be administered orally.

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (13)

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZA-SGS

Edegem, 2650, Belgium

Location

Hopital Beaujon

Clichy, 92110, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

New Zealand Clinical Research

Auckland, 1010, New Zealand

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

E-DA Hospital

Kaohsiung City, 82445, Taiwan

Location

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, 333, Taiwan

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 17, 2021
• Study Start: December 6, 2021
• Primary Completion: July 31, 2023
• Study Completion: June 26, 2024
• Last Updated: May 26, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

NZ (1); TW (2); GB (1); ES (2); BE (2); PL (1); IT (2); FR (2)