A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

NCT ID: NCT04129554

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-06
• Study Completion Date: 2022-06-09

Brief Summary

The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).

Detailed Description

Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

JNJ-73763989+ JNJ-56136379+ NA

Participants will receive fixed dose of JNJ-73763989 subcutaneous injection once every 4 weeks along with fixed dose of JNJ-56136379 tablet once daily and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\], or tenofovir alafenamide \[TAF\]) once daily up to 48 weeks.

Group Type: EXPERIMENTAL

JNJ-73763989

Intervention Type: DRUG

JNJ-73763989 injection will be administered subcutaneously once every 4 weeks up to 48 weeks.

JNJ-56136379

Intervention Type: DRUG

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

Entecavir (ETV) monohydrate

Intervention Type: DRUG

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

Tenofovir disoproxil fumarate (TDF)

Intervention Type: DRUG

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

Tenofovir alafenamide (TAF)

Intervention Type: DRUG

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

Placebo for JNJ-73763989+ Placebo for JNJ-56136379+ NA

Participants will receive matching placebo for JNJ-73763989 subcutaneous injection once every 4 weeks with matching placebo for JNJ-56136379 once daily and NA treatment (either ETV, TDF or TAF) once daily up to 48 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo for JNJ-73763989

Intervention Type: DRUG

Matching placebo for JNJ-73763989 will be administered as subcutaneous injection up to 48 weeks.

Placebo for JNJ-56136379

Intervention Type: DRUG

Matching placebo for JNJ-56136379 tablets will be administered orally up to 48 weeks.

Entecavir (ETV) monohydrate

Intervention Type: DRUG

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

Tenofovir disoproxil fumarate (TDF)

Intervention Type: DRUG

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

Tenofovir alafenamide (TAF)

Intervention Type: DRUG

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

Interventions

JNJ-73763989

JNJ-73763989 injection will be administered subcutaneously once every 4 weeks up to 48 weeks.

Intervention Type: DRUG

JNJ-56136379

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

Intervention Type: DRUG

Placebo for JNJ-73763989

Matching placebo for JNJ-73763989 will be administered as subcutaneous injection up to 48 weeks.

Intervention Type: DRUG

Placebo for JNJ-56136379

Matching placebo for JNJ-56136379 tablets will be administered orally up to 48 weeks.

Intervention Type: DRUG

Entecavir (ETV) monohydrate

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

Intervention Type: DRUG

Tenofovir disoproxil fumarate (TDF)

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

Intervention Type: DRUG

Tenofovir alafenamide (TAF)

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
• Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
• Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
• 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 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
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Exclusion Criteria

• 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 or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
• Evidence of liver disease of non-HBV etiology
• History or signs of cirrhosis or portal hypertension (nodules, no smooth liver contour, no normal portal vein, spleen size ≥12 cm) or signs of hepatocellular carcinoma (HCC)
• Significant laboratory abnormalities as defined in the protocol at screening
• Participants with a history of malignancy within 5 years before screening
• Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
• History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
• Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
• History of or current clinically significant skin disease or drug rash
• Known allergies, hypersensitivity, or intolerance to JNJ-73763989 and JNJ-56136379 or their excipients or to placebo content
• Contraindications to the use of entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) per local prescribing information
• Participants who have taken any therapies disallowed per protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

Cliniques Universitaires Saint Luc

Brussels, , Belgium

SGS Belgium NV

Edegem, , Belgium

UZ Antwerpen

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Hopital Beaujon

Clichy, , France

Hopital de La Croix Rousse

Lyon, , France

Hopital Saint Joseph

Marseille, , France

Hopital Cochin

Paris, , France

Chu Rennes Hopital Pontchaillou

Rennes, , France

CHU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Hopital Paul Brousse

Villejuif, , France

Universitatsklinikum Essen

Essen, , Germany

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, , Germany

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

ICH Study Center GmbH & Co. KG

Hamburg, , Germany

University Medical Center

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaetsklinikum Leipzig

Leipzig, , Germany

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, , Germany

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Irccs Ospedale Maggiore Di Milano

Milan, , Italy

Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara

Modena, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma

Rome, , Italy

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, , Poland

Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska

Gdansk, , Poland

ID Clinic

Mysłowice, , Poland

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, , Poland

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. Pta. de Hierro Majadahonda

Madrid, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Gral. Univ. Valencia

Valencia, , Spain

Queen Elizabeth Hospital

Birmingham, , United Kingdom

North Manchester General Hospital

Crumpsall, , United Kingdom

Glasgow Royal Infirmary

Glasgow, , United Kingdom

Grahame Hayton Unit

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

St Georges University of London and St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

Belgium; France; Germany; Italy; Poland; Spain; United Kingdom

References

Agarwal K, Buti M, van Bommel F, Lampertico P, Janczewska E, Bourliere M, Vanwolleghem T, Lenz O, Verbinnen T, Kakuda TN, Mayer C, Jezorwski J, Muenz D, Beumont M, Kalmeijer R, Biermer M, Lonjon-Domanec I. JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analogue-suppressed patients with chronic hepatitis B: REEF-2. J Hepatol. 2024 Sep;81(3):404-414. doi: 10.1016/j.jhep.2024.03.046. Epub 2024 Apr 5.

Reference Type: DERIVED

PMID: 38583491 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

73763989PAHPB2002

Identifier Type: OTHER

Identifier Source: secondary_id

2019-002674-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108679

Identifier Type: -

Identifier Source: org_study_id

NCT04288310

Identifier Type: -

Identifier Source: nct_alias