A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection

Percentage of participants meeting the NA treatment completion criteria at Week 48 were reported. A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (<) 3*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) < lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) <10 international units per milliliter (IU/mL). Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.

An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

An AE was any untoward medical occurrence in a clinical study participants administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs were defined as AEs with onset or worsening on or after date of first dose of study treatment.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.

An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that at any dose may result in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, and was medically important.

Percentage of participants with abnormalities in clinical laboratory tests (hematology: Abnormally low [AL] and Abnormally high [AH] basophils, eosinophils, erthrocytes mean corpuscular hemoglobin concentration, erthrocytes mean corpuscular heamoglobin, erthrocytes mean corpuscular volume, erthrocytes, hematocrit, lymphocytes atypical, metamyelocytes, monocytes, myelocytes, neutrophils, segmented, reticulocytes) were reported. Abnormality was determined at the investigator's discretion. Here, M.C: Mean corpuscular. Participants with abnormally low or high values were reported.

Percentage of participants with abnormalities in clinical laboratory tests (Chemistry: abnormally high and serum alpha fetoprotein, serum chloride, Serum gamma glutamyl tranferase [GGT], Serum high density cholesterol [HDL] Cholesterol, Indirect Bilirubin, Lactate Dehydrogenase, Serum Protein, Urea Nitrogen) were reported. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.

Percentage of participants with abnormalities in clinical laboratory tests(Urinalysis: abnormally high and low urine granular casts, urine hyaline casts, Urine Leukocytes,Urine Specific Gravity,Urine Squamous Epithelial cell, Urine T.E Cells, Urine Transitinoal erythrocyte count [E.C],Urine Tubular erthrocyte count ) were reported. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.

Percentage of participants with abnormalities in ECG parameters (heart rate, PR interval, QRS duration, and QTcF interval) were reported. Abnormality criteria: Heart rate abnormally low (AL): <45 beats per minute (bpm); PR interval AH:>220 msec; QRS duration AH:>120 msec; QTcF borderline prolonged (BP) QT: 450 msec to <=480 msec. Participants with abnormally low or high values were reported.

Percentage of participants with abnormalities in vital signs parameters (pulse rate, diastolic and systolic blood pressure) were reported. Abnormality criteria: Pulse rate AL:<=45 bpm; Systolic blood pressure (SBP) AL: <=90 millimeters of mercury (mmHg), mild:>140 mmHg to <160 mmHg; moderate:>=160 mmHg to <180 mmHg; Diastolic blood pressure (DBP): AL: <=150 mmHg; mild:>90 mmHg to <100 mmHg; moderate: >=100 mmHg to <110 mmHg; severe:>=110 mmHg. Abnormality was determined at the investigator's discretion. Participants with abnormally low or high values were reported.

Percentage of participants with HBsAg seroclearance 24 weeks after completion of all study intervention at Week 48 were reported. HBsAg seroclearance was defined as HBsAg (less than [<] lower limit of quantification LLOQ [0.05 IU/mL]). Responder was defined as a participant who achieved functional cure at Week 72. A participant was defined as having achieved functional cure at Week 72 if he/she: had met the criteria for stopping NA treatment at Week 48 and stopped treatment; had HBsAg seroclearance at Week 72 (that is, 24 weeks after stopping all study interventions); did not require NA re-treatment between Weeks 48 and 72. Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.

Percentage of participants with HBsAg seroclearance 48 weeks after completion of all study intervention at Week 48 were reported. HBsAg Seroclearance was defined as HBsAg <LLOQ (0.05 IU/mL). A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96. Multiple Imputation using a longitudinal multiple regression model was applied to impute missing data.

Percentage of participants with HBV DNA <LLOQ at 24 and 48 weeks after completion of all study intervention at Week 48 were reported. A responder was defined as a participant who achieved HBV DNA <LLOQ 24 and 48 weeks after stopping all study treatments at any time during the study and without restarting NA treatment thereafter.

Percentage of participants meeting the NA treatment completion criteria during follow-up were reported. A participant was defined as a responder in meeting the NA treatment completion criteria at Week 48, if the following criteria were met based on the clinical laboratory tests performed at Week 44: participants had alanine transaminase (ALT) less than (<) 3*upper limit of normal range (ULN); had hepatitis B virus deoxyribonucleic acid (HBV DNA) < lower limit of quantification (LLOQ); was hepatitis B e antigen (HBeAg)-negative; had hepatitis B surface antigen (HBsAg) <10 international units per milliliter (IU/mL). A responder was defined as a participant who stopped NA at Week 48 and met the NA treatment completion criteria at any time during the follow-up phase, regardless of the treatment duration.

Percentage of participants with HBsAg seroclearance after completion of NA treatment at Weeks 60, 84, and 96 were reported. Seroclearance of HBsAg was defined as HBsAg level <LLOQ (0.05 IU/mL). For Week 60: a responder was defined as a participant who achieved HBsAg seroclearance 12 weeks off treatment if the subject achieved HBsAg seroclearance 12 weeks after stopping; for Week 84:A responder was defined as a participant who achieved HBsAg seroclearance 36 weeks off-treatment if the participant achieved HBsAg seroclearance 36 weeks after stopping all study treatments; for Week 96:A responder was defined as a participant who achieved HBsAg seroclearance at Week 96 if the participant completed 48 weeks of treatment, met the criteria for stopping NA treatment at Week 48, did not require NA re-treatment between Week 48 and Week 96, and had HBsAg seroclearance at Week 96.

Percentage of participants who required NA re-treatment during follow-up were reported. Responder was defined as a participant who met the criteria for NA re-treatment at any time during follow-up, for those participants who met the NA treatment completion criteria at any time during the study and actually stopped NA treatment. NA re-treatment criteria: (1) Re-start NA treatment immediately with signs of decreasing liver function based on laboratory findings (eg, International Normalized Ratio [INR], direct bilirubin) or clinical assessment (eg, ascites, hepatic encephalopathy). (2) Immediately with an HBV DNA value of >100,000 IU/mL (irrespective of confirmation and/or ALT increase). (3) With confirmed post-treatment HBeAg seroreversion (HBeAg positive after it was negative at NA completion) (4) With confirmed* post-treatment increases in HBV DNA >2,000 IU/mL and ALT >5x ULN (5) With confirmed* post-treatment increases in HBV DNA >20,000 IU/mL.

Percentage of participants with flares (virologic, biochemical, and clinical) were reported. Virologic flare: confirmed HBV DNA >peak threshold ( 20,000 IU/mL 2,000 IU/mL and 200 IU/mL); biochemical Flare: confirmed ALT and/or AST increase of 3*ULN and 3*nadir; clinical flare: confirmed HBV DNA >peak threshold and confirmed ALT and/or AST increase of 3*ULN and 3*nadir. Virologic and clinical flare was assessed only for those participants who were off-treatment and had HBV DNA<LLOQ at the last observed time point on all study treatments and biochemical flares was identified on treatment and off treatment, respectively. Each virologic flare was categorized based on the confirmed (i.e., two consecutive values) peak HBV DNA above any of the three thresholds within the start and end date of that flare as follows: 20,000 IU/mL 2,000 IU/mL and 200 IU/mL. A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.

Number of participants with (sustained) reduction considering multiple markers were reported. HBV DNA results <LLOQ were reported as: (a) target detected, that is, traces of HBV DNA were detected/found but were too low to be quantified, or (b) target not detected, that is, no traces of HBV DNA were detected/found. LLOQ value for HBV DNA was 20 IU/mL.

HBsAg seroconversion was defined as achieving HBsAg seroclearance (HBsAg [quantitative] <LLOQ [0.05 IU/mL]) together with an appearance of anti-HBs antibodies (baseline anti-HBs antibodies [quantitative] <LLOQ and a post-baseline assessment greater than or equal to [>=] LLOQ).

HBeAg seroconversion was defined as achieving HBeAg seroclearance (HBeAg [quantitative] <LLOQ) together with an appearance of anti-HBe antibodies (baseline anti-HBe antibodies [qualitative] with a "negative" result and a post-baseline assessment with "positive" result.

Change from baseline in HBsAg levels was reported.

Change from baseline in HBeAg levels was reported.

Change from baseline in HBV DNA levels were reported.

Time to HBsAg seroclearance (defined as HBsAg level <LLOQ [0.05 IU/mL]) 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 to HBeAg seroclearance (defined as HBeAg level <LLOQ [0.11 IU/mL]) was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBeAg seroclearance.

Percentage of participants with HBsAg levels <100 IU/mL was reported.

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

Percentage of HBeAg-positive participants with HBeAg levels <LLOQ were reported.

Percentage of HBeAg-positive partcipants with HBeAg levels >1 log10 IU/mL were reported.

Percentage of participants with HBV DNA levels <LLOQ (20 IU/mL) were reported.

Mean change from baseline in ALT at EOT (Week 48) in participants with elevated ALT at baseline were reported.

Percentage of participants with ALT normalization was reported. A participant with ALT elevation at baseline was considered to achieve ALT normalization if his/her ALT value was <ULN at any given postbaseline analysis time point. A participant was defined as on treatment failure if he/she never met the criteria for stopping NA treatment during the study. A participant was defined as off-treatment failure if he/she required NA re-treatment after stopping all study interventions.

Virologic breakthrough was defined as having a confirmed on-treatment HBV DNA increase by >1 log10 from nadir (that is, lowest value during treatment) or a confirmed HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ (20 IU/mL). On-treatment was defined as the time period in which the participant received any of the study intervention.

Percentage of participants with undetectable HBV DNA levels after re-start of NA treatment during follow-up was reported.