A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection

NCT04585789 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR10879073763989HPB20032019-004475-39
• Study Type: interventional
• Target: 24
• Locations: 9 countries
• Sites: 10

Brief Summary

The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (7)

• Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40

  Absolute change from baseline to on-treatment liver biopsy timepoint (Week 40) in terms of the percentage of HBsAg-positive hepatocytes (at Week 40) were reported.

  Baseline, Week 40

• Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12

  Liver concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 - Molecules of JNJ-73763989 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 12 were reported.

  At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

• Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40

  Liver concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 40 were reported.

  At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

• Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12

  Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 12 were reported.

  At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

• Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40

  Plasma concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 40 were reported.

  At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

• Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12

  Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 12 were reported.

  Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

• Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40

  Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 40 were reported.

  Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Secondary Outcomes (34)

• Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48

  Follow-up Week 48

• Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance

  Follow-up Week 48

• Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance

  Follow-up Week 48

• Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40

  Baseline, Week 40

• Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40

  Baseline, Week 40

Study Arms (2)

Panel 1: JNJ-73763989+ NA

EXPERIMENTAL

Ongoing and new participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil or tenofovir alafenamide \[TAF\] tablets) once daily up to 48 weeks. Participants may receive optional treatment with pegylated interferon alpha-2a (PegIFN-alpha-2a) after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.

Drug: JNJ-73763989; Drug: JNJ-56136379; Drug: Entecavir (ETV); Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF); Drug: PegIFN-alpha-2a (Optional)

Panel 2: JNJ-73763989+ NA

EXPERIMENTAL

Ongoing and new participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) and NA treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks. Participants may receive optional treatment with PegIFN-alpha-2a after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.

Drug: JNJ-73763989; Drug: JNJ-56136379; Drug: Entecavir (ETV); Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF); Drug: PegIFN-alpha-2a (Optional)

Interventions

JNJ-73763989 DRUG

JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

JNJ-56136379 DRUG

JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

Entecavir (ETV) DRUG

ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

Tenofovir disoproxil DRUG

Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

Tenofovir alafenamide (TAF) DRUG

TAF will be administered orally once daily up to 48 weeks as NA treatment.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

PegIFN-alpha-2a (Optional) DRUG

PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.

Panel 1: JNJ-73763989+ NA; Panel 2: JNJ-73763989+ NA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
• Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos\[t\]ide analog \[NA\]) suppressed with HBeAg negative status
• Hepatitis B surface antigen (HBsAg) greater than (\>) 100 International Units per Milliliter (IU/mL) at screening
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m\^2), extremes included
• Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
• Fibroscan liver stiffness measurement less than and equal to (\<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of screening

You may not qualify if:

• Evidence of infection with hepatitis A, C, D or E virus infection or evidence of human immunodeficiency, virus type 1 (HIV-1) or HIV-2 infection at screening
• History or evidence of clinical signs/symptoms of hepatic decompensation including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
• History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening
• Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or equal to (\>=) 1.1\* upper limit of normal (ULN); (b) Partial thromboplastin time \>1.1\*ULN; (c) Any signs of prolonged bleeding (\>10 minutes)
• Presence of hemoglobinopathy (including sickle cell disease, thalassemia)
• Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (10)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Toronto General Hospital

Toronto, Ontario, ON M5G 2C4, Canada

Location

Hopital Beaujon

Clichy, 92110, France

Location

University Medical Center

Hamburg, D-20246, Germany

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

New Zealand Clinical Research

Auckland, 1010, New Zealand

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Grahame Hayton Unit

London, E1 1BB, United Kingdom

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

JNJ-56136379; entecavir; Tenofovir; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: As per protocol amendment-5, JNJ-56136379 has been removed as study intervention and all participants are counted as single arm in each panel.

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: October 14, 2020
• Study Start: March 11, 2021
• Primary Completion: February 8, 2023
• Study Completion: January 9, 2024
• Last Updated: May 21, 2025
• Results First Posted: March 5, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1); BE (1); FR (1); PL (1); IT (1); GB (2); DE (1); NZ (1); CA (1)