A Study of JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog (NA) With or Without JNJ-56136379 in Treatment-naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection

Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the study intervention. Treatment-emergent AEs are all AEs with an onset on or after the first administration of study treatment or any ongoing event that worsened in severity, intensity or frequency after the first administration of study treatment.

Number of participants with TESAEs were reported. was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the study intervention. Treatment-emergent AEs are all AEs with an onset on or after the first administration of study treatment or any ongoing event that worsened in severity, intensity or frequency after the first administration of study treatment. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Clinical laboratory test parameters were Hematology: absolute lymphocyte count, absolute neutrophil count (ANC), hemoglobin, Neutrophils Band Form, Neutrophils segmented, white blood cells (WBC) decreased, ; Chemistry: alanine aminotransferase (ALT) \& serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase (SGOT), cholesterol (fasting), creatinine Kinase, creatinine, GFR from Creatinine Adjusted for BSA, GFR from Cystatin C Adjusted for BSA, low-density lipoprotein (LDL), triglycerides (fasting); Urinalysis: glycosuria. DAIDS toxicity grades: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). Number of participants with treatment-emergent DAIDS toxicity Grade 3 or 4 were reported in this outcome measure.

Number of participants with worst treatment-emergent abnormality in ECG were reported. Treatment-emergent abnormality was defined as the abnormalities that were worsened as compared to the abnormality at baseline; which also included the shift from abnormally high to abnormally low and vice-versa. ECG parameters included heart rate (HR; abnormally low, HR <45 beats per minute (bpm) and (abnormally high HR>=120 bpm; PR interval abnormally high >220 milliseconds (ms): QRS interval abnormally high >=120 ms; QT corrected (Fridericia QTcF) categories; borderline prolonged QTc interval <450 to <=480 ms), prolonged QTc interval <480 to <=500 ms) and pathologically prolonged QTc interval >500 ms).

Number of participants with worst treatment-emergent abnormalities in vital signs were reported. Treatment-emergent abnormality was defined as the abnormalities that were worsened as compared to the abnormality at baseline; which also included the shift from abnormally high to abnormally low and vice-versa. Abnormalities in vital signs included abnormal pulse rate (PR); abnormally low, <=45 bpm and abnormally high >=120 bpm; diastolic blood pressure (DBP) abnormally low <=50 mmHg, systolic blood pressure (SBP) abnormally low <=90 mmHg. Additionally, abnormal low SBP and DBP were <=50 mmHg and <+90 mmHg. Only those categories in which at least one participant had data were reported.

Number of participants with clinically important treatment-emergent abnormalities in physical examination were reported.

Percentage of participants who reached HBsAg <10 IU/mL at the end induction phase were reported.

Time to achieve first occurrence of HBsAg <10 IU/mL were reported. Time to HBsAg <10 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 <10 IU/mL. Kaplan-Meier method was used for the estimation.

Percentage of participants meeting the protocol-defined NA treatment completion criteria at end of consolidation were reported. NA treatment completion criteria at CP Week 12 was defined as HBsAg <10 IU/mL; HBeAg-negative; HBV DNA <20 IU/mL, (that is, LLOQ); alanine aminotransferase(ALT) <3*ULN.

Percentage of participants with HBsAg seroclearance 48 weeks after stopping all study interventions at the consolidation phase and without restarting NA treatment during follow up phase were reported. HBsAg seroclearance was defined as (quantitative) HBsAg < LLOQ (HBsAg 0.05 IU/mL).

Percentage of participants with HBV DNA <LLOQ (<20 IU/mL) 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment during follow up phase were reported.

Number of participants with off-treatment virologic HBV flares were reported. Virologic flare was defined as confirmed HBV DNA >peak threshold (lowest peak to qualify as virologic flare was HBV DNA >200 IU/mL) in participants who were off-treatment and had HBV DNA <LLOQ (<20 IU/mL) at the last observed time point on all study treatments. The 3 thresholds of virologic flare was 20,000 IU/mL, 2,000 IU/mL and 200 IU/mL. Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. Off-treatment was defined as the time period after stopping all study treatments (including NA).

Number of participants with off-treatment biochemical HBV flares were reported. Biochemical flare was defined as first date of 2 consecutive visits with confirmed ALT and/or AST >=3*ULN and >=3*nadir (lowest value observed up to start of flare). Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. Off-treatment was defined as the time period after stopping all study treatments (including NA).

Number of participants with on-treatment biochemical HBV flares were reported. Biochemical flare was defined as first date of 2 consecutive visits with confirmed ALT and/or AST >=3*ULN and >=3*nadir (lowest value observed up to start of flare). Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. On-treatment was defined as the time period during which the participant received any of the study drugs.

Clinical flares occurred either when a virologic flare (confirmed HBV DNA >peak threshold) \& biochemical flare (ALT and/or AST >=3*ULN \& >=3*nadir [lowest value observed during off-treatment period up to time point of meeting the flare criteria]) overlapped in time or when a biochemical flare started within 4 weeks following the end of a virologic flare. The HBV DNA thresholds were: 20,000 IU/mL, 2,000 IU/mL and 200 IU/mL. Confirmed means that criteria was fulfilled at 2 or more consecutive time points or at last observed time point. Off-treatment was defined as time period after stopping all study drugs (including NA). The start date of a clinical flare was minimum start date of virologic flare and biochemical flare.

Percentage of participants who required NA re-treatment during follow-up phase were reported. A 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.

Percentage of participants with sustained (reduction) HBsAg response (per Definition 1) were reported. Sustained HBsAg response (definition 1) was defined as: For participants with FU Week 48 data: participants who had a >1 log10 decline from baseline in HBsAg and HBsAg <000 IU/mL at FU Week 48. For participants without FU Week 48 data: participants who had a HBsAg decline from baseline of >2 log10 at FU Week 24 or >1.5 log10 at FU Week 36 (most recent value used) and had HBsAg <1000 IU/mL at the last available timepoint.

Percentage of participants with sustained (reduction) HBsAg response (per Definition 2) were reported. Sustained HBsAg response (per Definition 2) was defined as: for participants with a >1 log decline in HBsAg from baseline at last follow-up visit: Among the most recent three visits, the difference between log10 HBsAg at 2 of 3 last visit and 1 of 3 last visit was <0.2, and the difference between log10 HBsAg at 3 of 3 last visit and 1 of 3 last visit was <0.2.

Percentage of participants with sustained (reduction) HBsAg response (per definition 3) were reported. Sustained HBsAg response (per Definition 3) was defined as: for participants with a >1 log decline in HBsAg from baseline at last follow-up visit: Among the most recent three visits, the difference between log10 HBsAg at 2 of 3 last visit and 1 of 3 last visit was <0.2, and the difference between log10 HBsAg at 3 of 3 last visit and 1 of 3 last visit was <0.2 and had an HBsAg <1000 IU/mL at the last available timepoint.

Percentage of participants with sustained (reduction) HBsAg response per Definition 4 were reported. Sustained HBsAg response (per Definition 4) was defined as stable level, decreasing level, and increasing level. Stable level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was within 0.2 log10. Decreasing level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was less than -0.2 log10. Increasing level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was more than 0.2 log10.

Percentage of Participants with HBsAg Seroclearance were reported. HBsAg seroclearance was defined as (quantitative) HBsAg level <LLOQ (<0.05 IU/mL).

Percentage of participants with HBeAg seroclearance were reported. HBeAg seroclearance was defined as (quantitative) HBeAg levels <LLOQ (<0.11 IU/mL).

Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance (defined as quantitative HBsAg <LLOQ [<0.05 IU/mL]) and appearance of anti-HBs antibodies (defined as a baseline anti-HBs antibodies [quantitative] <LLOQ [<5 milli-international units per milliliter (mIU/mL)] and a post-baseline assessment >=LLOQ [>=5 mIU/mL]).

Percentage of participants with HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as [quantitative] HBeAg <LLOQ [<0.11 IU/mL]) together with appearance of anti-HBe antibodies (defined as a baseline anti-HBe antibodies [qualitative] with a "negative" result and a post-baseline assessment with "positive" result).

Change from baseline over time in HBsAg levels at specified timepoints were reported

Change from baseline over time in HBsAg levels at specified timepoints were reported.

Change from baseline over time in HBV DNA Levels at Specified Timepoints were reported.

Time to achieve first HBsAg seroclearance (defined as quantitative HBsAg <LLOQ; HBsAg <0.05 IU/mL) were reported. Time to HBsAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance. Kaplan-Meier method was used for the estimation.

Time to achieve first occurrence of HBeAg seroclearance (HBeAg <LLOQ [<0.11 IU/mL]) were reported. Time to first occurrence of the HBeAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBeAg seroclearance.

Time to achieve first occurrence of HBV DNA < LLOQ (<20 IU/mL) were reported. Time to first occurrence of the HBV DNA < LLOQ was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBV DNA < LLOQ.

Percentage of participants with HBeAg levels below different cut-offs were reported. The cut-offs for HBeAg levels were : <LLOQ (<0.11 IU/mL), < 1 IU/mL, < 10 IU/mL, <100 IU/mL

Percentage of participants with HBsAg levels below different cut-offs were reported. The cut-offs for HBsAg level were: <LLOQ (<0.05 IU/mL), <1 IU/mL, <10 IU/mL, <100 IU/mL, <1000 IU/mL.

Percentage of participants with HBV DNA levels below cut-offs were reported. The cut-offs for HBV DNA were as follows: <LLOQ (<20 IU/mL) for target detected and not detected, < LLOQ for target not detected , and < LLOQ for target detected, <60 IU/mL, <100 IU/mL, <200 IU/mL, <1000 IU/mL, <2000 IU/mL, <20000 IU/mL.

Percentage of participants with virologic breakthrough on treatment were reported. Virological breakthrough was defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level < LLOQ (<20 IU/mL) or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level <LLOQ of the HBV DNA assay. Confirmed HBV DNA increase/level means that the criterion was fulfilled at 2 or more consecutive time points or at the last observed on-treatment time point.

Percentage of participants who reached HBV DNA undetectability after re-start of NA treatment during follow-up were reported. Undetectability of HBV DNA was defined as HBV DNA<LLOQ that is <20 IU/mL.

Cmax of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Noncompartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules

Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules.

Plasma concentration 24 hours after administration (C24h) of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted to analyze C24h of JNJ-73763989 and its molecules.

Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (molecules:JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted toanalyze AUC0 to 24h of JNJ-73763989 and its molecules.