Clinical trial NCT04129554: 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
Official title: A Randomized, Double Blind, Placebo-controlled Phase 2b Study to Evaluate Efficacy, Pharmacokinetics, and Safety of 48-week Study Intervention With 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Janssen Sciences Ireland UC
Sponsor class: INDUSTRY
First posted: 2019-10-17
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 72 Without Restarting NA Treatment
timeFrame: Week 72
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From screening up to Week 102
measure: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: From screening up to 102 weeks
measure: Percentage of Participants With HBsAg Seroclearance at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Less Than (<) Lower Limit of Quantification (LLOQ) at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Seroclearance at Week 96 (48 Weeks After Stopping All Study Interventions at Week 48 Without Restarting NA Treatment)
timeFrame: Week 96
measure: Percentage of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With HBsAg Seroconversion at Week 96
timeFrame: Week 96
measure: Change From Baseline in HBsAg Values at Weeks 48, 72, and 96
timeFrame: Baseline (Day 1), Weeks 48, 72, and 96
measure: Change From Baseline in HBV DNA Values at Weeks 48, 72, and 96
timeFrame: Baseline (Day 1), Weeks 48, 72, and 96
measure: Time to Achieve First HBsAg Seroclearance
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With Reduction of More Than (>) 1 log10 IU/mL in HBsAg Levels From Baseline
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With HBsAg Levels Less Than (<) 100 IU/mL at Weeks 48, 72, and 96
timeFrame: Weeks 48, 72, and 96
measure: Percentage of Participants With HBV DNA Levels Less Than (<) LLOQ From Baseline up to Week 96 (End of Study)
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With Flares
timeFrame: Baseline (Day 1) up to Week 96
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: Baseline (Day 1) up to Week 48
measure: Percentage of Participants Requiring NA Re-Treatment During Follow-up
timeFrame: Baseline (Day 1) up to Week 96
measure: Correlation Coefficient Between On-treatment HBsAg Change From Baseline With On-treatment HBV Blood Markers and Baseline Characteristics
timeFrame: Baseline (Day 1) to Week 96
measure: Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763976 (Molecule of JNJ-73763989)
timeFrame: Predose at Weeks 4, 8, 12, and 16
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989)
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763976 (Molecule of JNJ-73763989)
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763976 (Molecule of JNJ-73763989)
timeFrame: 24 hours postdose at Weeks 4, 8, 12, and 16
measure: Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-73763976 (Molecule of JNJ-73763989)
timeFrame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours of JNJ-73763976 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (AUC[0-24h], Dose Normalized)
timeFrame: 0 to 24 hours post-dose at Weeks 4, 8, 12, and 16
measure: Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763924 (Molecule of JNJ-73763989)
timeFrame: Predose at Weeks 4, 8, 12, and 16
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989)
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763924 (Molecule of JNJ-73763989)
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763924 (Molecule of JNJ-73763989)
timeFrame: 24 hours postdose at Weeks 4, 8, 12, and 16
measure: Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24h]) of JNJ-73763924 (Molecule of JNJ-73763989)
timeFrame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours of JNJ-73763924 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (AUC[0-24h], Dose Normalized)
timeFrame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16
measure: Observed Plasma Concentration at Predose (C[Predose]) of JNJ-56136379
timeFrame: Predose at Weeks 4, 8, 12, and 16
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-56136379
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-56136379
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Observed or Predicted Concentration at the End of a Dosing Interval (Ctau) of JNJ-56136379
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Area Under the Analyte Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCtau) of JNJ-56136379
timeFrame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: SGS Belgium NV
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Clichy
country: France
facility: Hopital Beaujon
city: Lyon
country: France
facility: Hopital de La Croix Rousse
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Paris
country: France
facility: Hopital Cochin
city: Rennes
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Vandoeuvre les Nancy
country: France
facility: CHU Nancy Brabois
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: ICH Study Center GmbH & Co. KG
city: Hamburg
country: Germany
facility: University Medical Center
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg Universitat Mainz
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Milano
country: Italy
facility: Irccs Ospedale Maggiore Di Milano
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena, Ospedale di Baggiovara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza w Bydgoszczy
city: Gdansk
country: Poland
facility: Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska
city: Myslowice
country: Poland
facility: ID Clinic
city: Wroclaw
country: Poland
facility: SP ZOZ Wroclawskie Centrum Zdrowia
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. Pta. de Hierro Majadahonda
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Hosp. Gral. Univ. Valencia
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Crumpsall
country: United Kingdom
facility: North Manchester General Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: London
country: United Kingdom
facility: Grahame Hayton Unit
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: St Georges University of London and St George's University Hospitals NHS Foundation Trust
Study officials:
affiliation: Janssen Sciences Ireland UC
name: Janssen Sciences Ireland UC Clinical Trial
role: STUDY_DIRECTOR
References: