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

NCT04129554 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR10867973763989PAHPB20022019-002674-31
• Study Type: interventional
• Target: 130
• Locations: 7 countries
• Sites: 41

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).

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 Without Restarting NA Treatment

  Percentage of participants with HBsAg seroclearance at Week 72 (24 weeks after completion of all study interventions at Week 48) without restarting NA treatment was reported. Seroclearance at Week 72 of the treatment defined as a confirmed loss of HBsAg at Week 72. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result.

  Week 72

Secondary Outcomes (36)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  From screening up to Week 102

• Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)

  From screening up to 102 weeks

• Percentage of Participants With HBsAg Seroclearance at Week 48

  Week 48

• Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Less Than (<) Lower Limit of Quantification (LLOQ) at Week 48

  Week 48

• Percentage of Participants With HBsAg Seroclearance at Week 96 (48 Weeks After Stopping All Study Interventions at Week 48 Without Restarting NA Treatment)

  Week 96

Study Arms (2)

JNJ-73763989+ JNJ-56136379+ NA

EXPERIMENTAL

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.

Drug: JNJ-73763989; Drug: JNJ-56136379; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil fumarate (TDF); Drug: Tenofovir alafenamide (TAF)

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

PLACEBO COMPARATOR

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.

Drug: Placebo for JNJ-73763989; Drug: Placebo for JNJ-56136379; Drug: Entecavir (ETV) monohydrate; Drug: Tenofovir disoproxil fumarate (TDF); Drug: Tenofovir alafenamide (TAF)

Interventions

JNJ-73763989 DRUG

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

JNJ-73763989+ JNJ-56136379+ NA

JNJ-56136379 DRUG

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

JNJ-73763989+ JNJ-56136379+ NA

Placebo for JNJ-73763989 DRUG

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

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

Placebo for JNJ-56136379 DRUG

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

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

Entecavir (ETV) monohydrate DRUG

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

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

Tenofovir disoproxil fumarate (TDF) DRUG

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

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

Tenofovir alafenamide (TAF) DRUG

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

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

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 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

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (41)

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

SGS Belgium NV

Edegem, 2650, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Hopital Beaujon

Clichy, 92110, France

Location

Hopital de La Croix Rousse

Lyon, 69004, France

Location

Hopital Saint Joseph

Marseille, 13008, France

Location

Hopital Cochin

Paris, 75014, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Hopital Paul Brousse

Villejuif, 94800, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

ICH Study Center GmbH & Co. KG

Hamburg, 20146, Germany

Location

University Medical Center

Hamburg, D-20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, 55131, Germany

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98124, Italy

Location

Irccs Ospedale Maggiore Di Milano

Milan, 20122, Italy

Location

Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara

Modena, 41126, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56124, Italy

Location

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

Rome, 00161, Italy

Location

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy

Bydgoszcz, 85-030, Poland

Location

Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska

Gdansk, 80-462, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

SP ZOZ Wroclawskie Centrum Zdrowia

Wroclaw, 50-136, Poland

Location

Hosp Clinic de Barcelona

Barcelona, 8028, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. Pta. de Hierro Majadahonda

Madrid, 28222, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Hosp. Gral. Univ. Valencia

Valencia, 46014, Spain

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

North Manchester General Hospital

Crumpsall, M8 5RB, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G31 2ER, United Kingdom

Location

Grahame Hayton Unit

London, E1 1BB, United Kingdom

Location

Kings College Hospital

London, SE5 9RF, United Kingdom

Location

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

London, SW17 0RE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38583491 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

JNJ-56136379; entecavir; Tenofovir; tenofovir alafenamide

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

Results Point of Contact

• Title: Study Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 17, 2019
• Study Start: November 6, 2019
• Primary Completion: July 8, 2021
• Study Completion: June 9, 2022
• Last Updated: February 4, 2025
• Results First Posted: July 31, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (5); DE (8); IT (5); GB (6); FR (7); ES (6); PL (4)