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

Janssen Sciences Ireland UC130 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

130

Conditions

Hepatitis B, Chronic

Interventions

JNJ-73763989DRUG

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

JNJ-56136379DRUG

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

Placebo for JNJ-73763989DRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (41)

Outcomes

Primary Outcomes

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.

Time frame: Week 72

Secondary Outcomes

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

An adverse event (AE) was any untoward medical occurrence in a clinical study participant who was administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE was defined as the AEs occurring after first administration of study intervention (or worsened since then).

Time frame: From screening up to Week 102

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

An AE was any untoward medical occurrence in a clinical study participant who was administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE was defined as the AEs occurring after first administration of study intervention (or worsened since then). SAEs included any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the off spring of a study participant.

Time frame: From screening up to 102 weeks

Percentage of Participants With HBsAg Seroclearance at Week 48

Percentage of participants with hepatitis B surface antigen (HBsAg) seroclearance at Week 48 was reported. Seroclearance at Week 48 of the treatment defined as a confirmed loss of HBsAg at Week 48. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

Entecavir (ETV) monohydrateDRUG

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

Tenofovir disoproxil fumarate (TDF)DRUG

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

Tenofovir alafenamide (TAF)DRUG

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

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

...and 31 more locations

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

Percentage of participants with HBV DNA \<LLOQ (20 international units per milliliters \[IU/mL\]) at Week 48 was reported.

Time frame: 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)

Percentage of participants with HBsAg seroclearance at Week 96 (48 weeks after stopping all study interventions at Week 48 without restarting NA treatment) was reported. Seroclearance at Week 96 of the treatment defined as a confirmed loss of HBsAg at Week 96. Loss is defined as a baseline HBsAg with a repeat reactive, confirmed or positive result and a post-baseline assessment with a negative result. Missing values were imputed by last observation carried forward (LOCF).

Time frame: Week 96

Percentage of Participants With (Sustained) Reduction, Suppression, and/or Seroclearance

Percentage of participants with (sustained) reduction, suppression, and/or seroclearance considering single and multiple markers (such as hepatitis B surface antigen \[HBsAg\] and HBV DNA) (HBsAg \>= lower limit of quantification \[LLOQ\] and HBV DNA\<2000 IU/mL; HBsAg \>= LLOQ and LLOQ \<= HBV DNA \< 2000 IU/mL) off-treatment was reported.

Time frame: Baseline (Day 1) up to Week 96

Percentage of Participants With HBsAg Seroconversion at Week 96

Percentage of participants with HBsAg seroconversion were reported. HBsAg seroconversion was defined as HBsAg seroclearance together with appearance of anti-hepatitis B surface (HBs) or anti-hepatitis e (HBe) antibodies, respectively.

Time frame: Week 96

Change From Baseline in HBsAg Values at Weeks 48, 72, and 96

Change from baseline in HBsAg values was reported.

Time frame: Baseline (Day 1), Weeks 48, 72, and 96

Change From Baseline in HBV DNA Values at Weeks 48, 72, and 96

Change from baseline in HBV DNA values was reported. Participants were considered as virologically suppressed if they were on stable HBV treatment (receiving NA treatment \[ETV, TDF, or TAF)\] for at least 24 months prior to screening and were on the same dose of NA treatment regimen for at least 3 months at the time of screening, and had serum HBV DNA less than (\<)60 IU/mL on 2 sequential measurements at least 6 months and had documented alanine aminotransferase values \<2.0\* upper limit of normal on 2 sequential measurements at least 6 months apart.

Time frame: Baseline (Day 1), Weeks 48, 72, and 96

Time to Achieve First HBsAg Seroclearance

Time to achieve first HBsAg seroclearance was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBsAg seroclearance.

Time frame: Baseline (Day 1) up to Week 96

Percentage of Participants With Reduction of More Than (>) 1 log10 IU/mL in HBsAg Levels From Baseline

Percentage of participants with reduction of \>1 log10 in HBsAg Levels IU/mL from baseline was reported.

Time frame: Baseline (Day 1) up to Week 96

Percentage of Participants With HBsAg Levels Less Than (<) 100 IU/mL at Weeks 48, 72, and 96

Percentage of participants with HBsAg Levels \<100 IU/mL at Weeks 48, 72, and 96 was reported.

Time frame: Weeks 48, 72, and 96

Percentage of Participants With HBV DNA Levels Less Than (<) LLOQ From Baseline up to Week 96 (End of Study)

Percentage of Participants with HBV DNA levels \<LLOQ (20 IU/mL) was reported.

Time frame: Baseline (Day 1) up to Week 96

Percentage of Participants With Flares

Percentage of participants with flares (virologic, biochemical and clinical flares) was reported. Biochemical flare was defined as confirmed alanine transaminase flare and/or aspartate aminotransferase flare \>=3\*upper limit of normal and \>=3\*nadir. The start of a confirmed virologic flare was defined as the first date of two consecutive visits with HBV DNA \>200 IU/mL. The end date of the same confirmed virologic flare was defined as the first date when HBV DNA value returns to less than or equal to (\<=)200 IU/mL or the date of NA treatment restart, whichever comes first. Clinical flare was defined as participants with both virologic and biochemical flare.

Time frame: Baseline (Day 1) up to Week 96

Percentage of Participants With Virologic Breakthrough

Percentage of participants with virologic breakthrough defined as confirmed on-treatment HBV DNA increase by more than (\>) 1 log10 IU/mL from nadir level or confirmed on treatment level \>200 IU/mL in participants who had HBV DNA level below \<LLOQ of the HBV DNA assay was reported.

Time frame: Baseline (Day 1) up to Week 48

Percentage of Participants Requiring NA Re-Treatment During Follow-up

Percentage of participants requiring NA re-treatment (either ETV, TDF, or TAF) during follow-up was reported.

Time frame: Baseline (Day 1) up to Week 96

Correlation Coefficient Between On-treatment HBsAg Change From Baseline With On-treatment HBV Blood Markers and Baseline Characteristics

Correlation coefficient between on-treatment HBsAg change from baseline with on-treatment HBV blood markers and baseline characteristics was reported at different timepoints (against age, baseline NA treatment duration, HBsAg value at baseline, HBsAg values at Weeks 24 and 48).

Time frame: Baseline (Day 1) to Week 96

Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763976 (Molecule of JNJ-73763989)

C(predose) was defined as the observed plasma concentration of JNJ-73763976 (a molecule of JNJ-73763989) at predose of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Predose at Weeks 4, 8, 12, and 16

Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989)

Cmax was defined as the maximum observed concentration of JNJ-73763976 (molecule of JNJ-73763989). PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763976 (Molecule of JNJ-73763989)

tmax was defined as the time to reach the maximum observed plasma concentration of JNJ-73763976 (molecule of JNJ-73763989). PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763976 (Molecule of JNJ-73763989)

C(24h) was defined as the observed plasma concentration of JNJ-73763976 (a molecule of JNJ-73763989) at 24 h postdose of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 24 hours postdose at Weeks 4, 8, 12, and 16

Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-73763976 (Molecule of JNJ-73763989)

AUC(0-24h) was defined as the area under the concentration of JNJ-73763976 (a molecule of JNJ-73763989) versus time curve from time 0 to 24 hours of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16

Maximum Observed Analyte Concentration (Cmax) of JNJ-73763976 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])

Cmax(Dose Normalized) was defined as the maximum observed concentration of JNJ-73763976 (a molecule of JNJ-73763989) dose normalized to 1 mg. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

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)

AUC(\[0-24h\], Dose Normalized) was defined as the area under the concentration of JNJ-73763976 (molecule of JNJ-73763989) versus time curve from time 0 to 24 hours of JNJ-73763989 dose normalized to 1 mg. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 0 to 24 hours post-dose at Weeks 4, 8, 12, and 16

Observed Plasma Concentration at Predose (C[Predose]) of JNJ-73763924 (Molecule of JNJ-73763989)

C(predose) was defined as the observed plasma concentration of JNJ-73763924 (a molecule of JNJ-73763989) at predose of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Predose at Weeks 4, 8, 12, and 16

Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989)

Cmax was defined as the maximum concentration of JNJ-73763924 (molecule of JNJ-73763989). PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763924 (Molecule of JNJ-73763989)

tmax was defined as the time to reach the maximum observed plasma concentration of JNJ-73763924 (molecule of JNJ-73763989). PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Observed Plasma Concentration at 24 Hour Postdose (C[24h]) of JNJ-73763924 (Molecule of JNJ-73763989)

C(24h) was defined as the observed plasma concentration of JNJ-73763924 (molecule of JNJ-73763989) at 24 h postdose of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 24 hours postdose at Weeks 4, 8, 12, and 16

Area Under the Analyte Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24h]) of JNJ-73763924 (Molecule of JNJ-73763989)

AUC(0-24h) was defined as the area under the concentration of JNJ-73763924 (molecule of JNJ-73763989) versus time curve from time 0 to 24 hour of JNJ-73763989. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16

Maximum Observed Analyte Concentration (Cmax) of JNJ-73763924 (Molecule of JNJ-73763989) Dose Normalized to 1 mg (Cmax[Dose Normalized])

Cmax(Dose Normalized) was defined as the maximum observed analyte concentration of JNJ-73763924 (molecule of JNJ-73763989) dose normalized to 1 mg. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

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)

AUC(\[0-24h\], Dose Normalized) was defined as the area under the analyte concentration JNJ-73763924 (a molecule of JNJ-73763989) versus time curve from time 0 to 24 hours of JNJ-73763989 dose normalized to 1 mg. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: 0 to 24 hours postdose at Weeks 4, 8, 12, and 16

Observed Plasma Concentration at Predose (C[Predose]) of JNJ-56136379

C(predose) was defined as the observed plasma concentration at predose of JNJ-56136379. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Predose at Weeks 4, 8, 12, and 16

Maximum Observed Analyte Concentration (Cmax) of JNJ-56136379

Cmax was defined as the maximum observed concentration of JNJ-56136379. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-56136379

tmax was defined as the time to reach the maximum observed plasma concentration of JNJ-56136379. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Observed or Predicted Concentration at the End of a Dosing Interval (Ctau) of JNJ-56136379

Ctau was defined as the observed or predicted concentration at the end of a dosing interval of JNJ-56136379. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose

Area Under the Analyte Concentration Versus Time Curve During a Dosing Interval at Steady State (AUCtau) of JNJ-56136379

AUCtau was defined as the area under the analyte concentration versus time curve during a dosing interval at steady state of JNJ-56136379. PK sample collection was done based on the availability of the participants at Weeks 4, 8, 12, or 16 and thus collected data were averaged and reported in this outcome measure.

Time frame: Weeks 4, 8, 12, and 16: at Predose, 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose