Hepatitis B
Conditions
Brief summary
The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.
Detailed description
The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.
Interventions
DRUGJNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.
DRUGJNJ-56136379
JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.
DRUGEntecavir (ETV)
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.
DRUGTenofovir disoproxil
Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.
TAF will be administered orally once daily up to 48 weeks as NA treatment.
DRUGPegIFN-alpha-2a (Optional)
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
As per protocol amendment-5, JNJ-56136379 has been removed as study intervention and all participants are counted as single arm in each panel.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening * Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos\[t\]ide analog \[NA\]) suppressed with HBeAg negative status * Hepatitis B surface antigen (HBsAg) greater than (\>) 100 International Units per Milliliter (IU/mL) at screening * Body mass index (BMI) between 18.0 and 35.0 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 * Fibroscan liver stiffness measurement less than and equal to (\<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of 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 * History or signs of cirrhosis or portal hypertension, signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities on an abdominal ultrasound performed within 6 months prior to screening or at the time of screening * Presence of coagulopathy or bleeding disorder as indicated by: (a) International normalized ratio (INR) greater than or equal to (\>=) 1.1\* upper limit of normal (ULN); (b) Partial thromboplastin time \>1.1\*ULN; (c) Any signs of prolonged bleeding (\>10 minutes) * Presence of hemoglobinopathy (including sickle cell disease, thalassemia) * Liver biopsy performed prior to screening that led to complications and that in the opinion of the investigator would prohibit another liver biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 | Baseline, Week 40 | Absolute change from baseline to on-treatment liver biopsy timepoint (Week 40) in terms of the percentage of HBsAg-positive hepatocytes (at Week 40) were reported. |
| Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12 | At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Liver concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 - Molecules of JNJ-73763989 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 12 were reported. |
| Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40 | At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Liver concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 40 were reported. |
| Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12 | At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 12 were reported. |
| Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40 | At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Plasma concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 40 were reported. |
| Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 | Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 12 were reported. |
| Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 | Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989) | Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 40 were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48 | Follow-up Week 48 | Percentage of participants with sustained (reduction) serum HBsAg response per Definition 2 at follow-up Week 48 were reported. Sustained serum 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 log HBsAg at 2 of 3 last visit and 1 of 3 last visit is \<0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is \<0.2. |
| Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance | Follow-up Week 48 | Percentage of Participants who achieved HBsAg Seroclearance were reported. HBsAg seroclearance was defined as quantitative HBsAg \<LLOQ (\<0.05 IU/mL). |
| Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance | Follow-up Week 48 | Percentage of Participants who achieved HBeAg Seroclearance were reported. HBeAg seroclearance was defined as (quantitative\] HBeAg \<LLOQ (\<0.11 IU/mL); with HBeAg positive status at baseline and became HBeAg negative post-baseline. |
| Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40 | Baseline, Week 40 | Change from baseline in percentage of intrahepatic viral parameter: HBcAg positive hepatocytes at Week 40 were reported. The percentage of HBcAg positive hepatocytes were derived as number of HBcAg positive hepatocytes\*100 per total number of evaluated hepatocytes. |
| Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40 | Baseline, Week 40 | Change from baseline in percentage of intrahepatic viral parameter: cccDNA positive hepatocytes were reported. The percentage of cccDNA-positive hepatocytes, were derived as number of cccDNA positive hepatocytes\*100 per total number of evaluated hepatocytes. |
| Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40 | Baseline, Week 40 | Change from baseline in percentage of intrahepatic viral parameter: HBsAg positive hepatocytes at Week 40 were reported. The percentage of HBsAg positive hepatocytes were derived as number of HBsAg positive hepatocytes \* 100 per total number of evaluated hepatocytes. |
| Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40 | Baseline, Week 40 | Change from baseline in percentage of intrahepatic viral Parameter: pgRNA positive hepatocytes at Week 40 were reported. The percentage of pgRNA-positive hepatocytes, were derived as number of pgRNA positive hepatocytes\*100 per total number of evaluated hepatocytes. |
| Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40 | Baseline, Week 40 | Change from baseline in transcriptional activity (ratio of pgRNA/cccDNA) at Week 40 were reported. |
| Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40 | Baseline, Week 40 | Change from baseline in percentage of intrahepatic viral parameter: silent infected hepatocytes (that is infected hepatocytes without HBV transcription; cccDNA-positive/HBV RNA-negative hepatocytes) at Week 40 were reported. The percentage of silent infected hepatocytes (SIH), were derived as number of silent infected hepatocytes\*100 per total number of evaluated hepatocytes. |
| Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment | At Week 72 (24 weeks after completion of all study drugs at Week 48) | Percentage of participants with HBsAg seroclearance (defined as HBsAg \< LLOQ: 0.05 IU/mL) at Week 72 without restarting NA treatment were reported. |
| Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48 | Follow-up Week 48 | Percentage of participants with sustained (reduction) serum HBsAg response per Definition 1 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 1 was defined as: for participants with data for last follow-up visit (Follow-up Week 48 for participants who did not receive PegIFN-alpha2a or received PegIFN-alpha2a and did not meet NA completion criteria, and last Follow-up visit for participants who received PegIFN-alpha2a and stopped NA during Follow-up): participants who had a \>1 log decline in HBsAg response at last scheduled follow-up visit and had an HBsAg \<1000 IU/mL at last scheduled follow-up visit, or for participants without data at last follow-up visit: HBsAg values had a \>2 log decline at second most recent visit or \>1.5 log decline at latest visit (most recent value used) compared to baseline and had an HBsAg \<1000 IU/mL at last available timepoint. |
| Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48 | From follow-up Week 24 up to follow-up Week 48 | Percentage of participants with sustained (reduction) serum HBsAg response per Definition 3 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 3 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 log HBsAg at 2 of 3 last visit and 1 of 3 last visit is \<0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is \<0.2 and have an HBsAg \<1000 IU/mL at the last available timepoint. |
| Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Follow-up Week 48 | Percentage of participants with sustained (reduction) serum HBsAg response per definition 4 follow-up Week 48 were reported. Sustained serum HBsAg response per definition 4 were classified into 3 categories with respect to the difference between HBsAg level at the last Follow-up timepoint and end of treatment: Increase: \>+0.2 log10 IU/mL , stable: within plus or minus (+/-) 0.2 log10 IU/mL, and decrease: \>-0.2 log10 IU/mL. |
| Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion | From baseline (Day 1) up to follow-up Week 48 | 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 \[\>=5 mIU/mL\]). |
| Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion | From baseline (Day 1) up to follow-up Week 48 | Percentage of participants who achieved HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as \[quantitative\] HBeAg \<LLOQ \[\<0.11 IU/mL\]; with HBeAg positive status at baseline and became HBeAg negative post-baseline) 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). |
| Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | From baseline (Day 1) up to follow-up Week 48 | Virologic flare (VF) per derivation 1 was defined only for participants who were off-treatment (period after stopping all study drugs, including NA) and who had HBV DNA\<LLOQ (\<20 IU/mL) at last observed point on-treatment \[OT\]); start date of confirmed VF was first date of 2 consecutive visits with HBV DNA \>200 IU/mL. End date of same confirmed VF was first date when HBV DNA value returns to \<=200 IU/mL or date of NA restart, whichever comes first. Each virologic flare were categorized based on confirmed (that is, 2 consecutive values) peak HBV DNA above any of 3 thresholds within the start and end date of that flare as followed: 20,000 IU/mL, 2,000 IU/mL, and 200 IU/mL. Participants were counted only once for any given flare, regardless of the number of times they actually experienced the flare. |
| Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | From baseline (Day 1) up to follow-up Week 48 | Off-treatment (time period after stopping all study drugs \[including NA\]) biochemical flare was defined as first date of 2 consecutive visits with ALT and/or AST \>=3\*ULN and \>=3\*nadir (lowest value observed up to start of flare) while participant received no study drugs. End date of same off-treatment biochemical flare was defined as first date with 50 percentage (%) reduction from peak ALT and/or AST level & \<3\*ULN. On-treatment (time period during which the participant received any of study drugs) biochemical flare was defined as first date of 2 consecutive visits with ALT and/or AST \>=3\*ULN and \>=3\*nadir (lowest value observed up to start of flare) while participant was on-treatment. End date of same on-treatment biochemical flare was defined as first date with a 50% reduction from the peak ALT and/or AST level and \<3\*ULN, regardless of stopping study drugs. Participants were counted only once for any given flare, regardless of the number of times they actually experienced flare. |
| Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | From baseline (Day 1) up to follow-up Week 48 | Percentage of participants with off-treatment clinical flares were reported. Clinical flares occurred either when a virologic flare and biochemical flare overlapped in time or when a biochemical flare started within 4 weeks following the end of a virologic flare. Off-treatment was defined as the time period after stopping all study drugs (including NA). The start date of a clinical flare was the minimum start date of the virologic flare and biochemical flare. The end date of a clinical flare was the maximum end date of the virologic flare and biochemical flare, that is, the later date between HBV DNA returned to \<=200 IU/mL (or \<=1 log10) and 50 %reduction from the peak ALT and/or AST level and \<3\*ULN reached during the biochemical flare. Participants were counted only once for any given flare, regardless of the number of times they actually experienced the flare. |
| Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance | From baseline (Day 1) up to follow-up Week 48 | Time to first occurrence of HBsAg seroclearance (defined as quantitative HBsAg \<LLOQ \[\<0.05 IU/mL\]) were reported. Time to first occurrence of 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 the HBsAg seroclearance. Participants who withdrew early from the study before achieving HBsAg seroclearance or who did not achieve HBsAg seroclearance were censored at the last available HBsAg assessment. Kaplan-Meier method was used for the estimation. |
| Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough | From baseline (Day 1) up to follow-up Week 48 | Percentage of participants with virologic breakthrough on treatment were reported. Virological breakthrough was defined as having a 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 (\<20 IU/mL) of the HBV DNA assay. Confirmed HBV DNA increase/level means that the criterion should be fulfilled at 2 or more consecutive time points or at the last observed on-treatment time point. On treatment was defined as the time period in which the participant received any of the study interventions (JNJ-3989 and/or JNJ 6379 and/or NA and/or PegIFN-alpha2a). |
| Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48 | Percentage of participants with TEAES (including serious and non-serious) and TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. 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. |
| Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open-label: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24 | Number of participants with HBV-specific peripheral blood T-cell responses were reported. HBV-specific T-cells were characterized in peripheral blood mononuclear cell immune analysis by binding assays (multimer staining) combined with downstream T-cell responses and transcriptome profiling. |
| Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48 | Clinical laboratory test parameters were Hematology : absolute neutrophil count (ANC); Chemistry : alanine aminotransferase (ALT) and serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase(AST) or serum glutamic oxaloacetic transaminase (SGOT), amylase (pancreatic and total), creatinine Kinase, creatinine, low-density lipoprotein (LDL), lipase, estimated glomerular filtration rate (eGFR) on serum creatinine (Cr). DAIDS toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). Percentage of participants with treatment-emergent DAIDS toxicity Grade 3 or 4 were reported in this outcome measure. For toxicity grades, treatment-emergent was concluded if the postbaseline grade was worse than the baseline grade. Only those abnormality categories in which at least one participant had data were reported. |
| Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48 | ECG parameters included ECG mean heart rate (HR)(beats per minute\[bpm\]), Pulse rate (PR) interval (milliseconds \[ms\]), QRS duration (ms) and QTc Corrected (Fridericia's formula QTcF). Abnormalities were graded as follows: ECG mean heart rate (abnormally low HR \<45 bpm) and (abnormally high HR\>=120 bpm); PR interval (abnormally high \>220 ms) and QPRS (abnormally high \>=120 ms); OT interval corrected for heart rate according to Fridericia (QTcF); borderline prolonged (BRD Pr )QTc (\>=450 to \<=480 ms), prolonged QTc (\>=480 to \<=500 ms)and pathologically prolonged QTc (\>500 ms). For worst abnormality, treatment-emergent was concluded if the abnormality worsened as compared to the abnormality at baseline: abnormally high to abnormally low and vice-versa. Only those abnormality categories in which at least one participant had data were reported. |
| Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48 | Percentage of participants with worst treatment-emergent DAIDS toxicity grade in vital signs were reported. Abnormality grades were: pulse rate (abnormally low \<=45 bpm) and (abnormally high \>=120 bpm). An assessment was treatment-emergent if abnormality worsened as compared to the abnormality at baseline: from abnormally high to abnormally low and vice-versa. Only the category (pulse rate) in which at least one participant had data were reported. |
| Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48 | Number of participants with clinically significant treatment-emergent abnormalities in physical examination were reported. Physical examination included head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological examinations. |
| Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 : Pre-dose on Day 29 | Plasma trough concentration (C\[0hour\]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. C0h was the pre-dose plasma concentration of the JNJ-73763989 (JNJ-73763976, JNJ-73763924). Non-compartmental analysis were conducted to analyze plasma concentration of JNJ-73763989 and its molecules. |
| Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Maximum observed plasma concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules. |
| Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Maximum observed plasma concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules. |
| Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Minimum observed plasma concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmin of JNJ-73763989 and its molecules |
| Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) | Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours) | Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules. |
| Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours) | Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules. |
| Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze AUC0 to 24h of JNJ-73763989 and its molecules. |
| Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose | Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze AUC0 to 24h of JNJ-73763989 and its molecules. |
Countries
Belgium, Canada, France, Germany, Italy, New Zealand, Poland, United Kingdom, United States
Participant flow
Recruitment details
Study consisted of 3 Panels (1, 2 and 3). Panel 1: participants with hepatitis B (HB) e antigen (HBeAg) positive and not treated. Panel 2: participants with HBeAg negative and virologically suppressed by entecavir (ETV), tenofovir disoproxil (TD), or tenofovir alafenamide (TAF) treatment. Panel 3: participants with HBeAg positive or negative who were either not treated or virologically suppressed by ETV or TD treatment.
Pre-assignment details
As per protocol amendment (PA) 5 (dated 01 October 2021), all participants stopped JNJ-56136379 (JNJ-6379) treatment and continued treatment with JNJ-73763989 (JNJ-3989) plus nucleos(t)ide analog (NA; ETV, TD, or TAF) plus optional pegylated interferon alpha-2a (PegIFN-alpha2a). The study consisted of 3 phases: screening phase, open-label (OL) intervention phase and follow-up (FU) phase.
Participants by arm
| Arm | Count |
|---|---|
| Panel 1 Prior to PA 5, participants received either JNJ-3989 200 milligrams (mg) subcutaneous(SC) injection every 4 weeks(Q4W) from Day 1 (Week 1) to Week 44+JNJ-6379 250 mg once daily(QD)+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48 or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44+NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, participants stopped JNJ-6379 and continued JNJ-3989+NA. With separate consent, participants received optional treatment:PegIFN-alpha-2a 180 micrograms(mcg) SC injection once weekly(QW) post Week 40 liver biopsy for either 12/24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all participants entered FU phase; stopped JNJ-3989/JNJ-6379 and NA ( if NA completion criteria \[NAcc:alanine aminotransferase {ALT} less than {\<}3\*upper limit of normal{ULN}, HB virus deoxyribonucleic acid {HBV DNA} \<lower limit of quantification {LLOQ}:20 International Units per milliliter {IU/mL}\], HBeAg negative & HB surface antigen {HBsAg} \<10 IU/mL\] was met as per Week 44 laboratory tests). If NAcc were not met, NA was continued till FU end (study Week 96). Participants on PegIN-alpha2a and who had not met NAcc at Week 48 were assessed at PegIN-alpha2a treatment end and stopped NA, if NAcc was met; then entered FU. If NA-retreatment criteria (HBV DNA \>20,000 IU/mL, HBV DNA \>2,000 IU/mL but \<20,000 IU/mL & ALT \>5\*ULN) was met in FU, NA was re-started. | 10 |
| Panel 2 Prior to PA 5, participants received either JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + JNJ-6379 250 mg QD and NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48, or JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. After PA 5, participants discontinued JNJ-6379 and continued JNJ-3989 + NA. With separate consent, participants received optional treatment with PegIFN-alpha-2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all participants entered FU phase and stopped JNJ-3989/JNJ-6379 and NA (if NA treatment completion criteria \[ALT \<3\*ULN, HBV DNA \<LLOQ; 20 IU/mL, HBeAg negative and HBsAg \<10 IU/mL\] was met as per Week 44 laboratory tests). If NA completion criteria were not met, NA was continued till FU phase end (study Week 96). Participants on PegIN-alpha2a and who had not met NA completion criteria at Week 48 were assessed at end of PegIN-alpha2a treatment and stopped NA, if completion criteria met and then entered FU phase. If NA-retreatment criteria (HBV DNA \>20,000 IU/mL, HBV DNA \>2,000 IU/mL but \<20,000 IU/mL and ALT \>5\*ULN) were met in FU phase, NA retreatment was started. | 10 |
| Panel 3 After PA 5, participants received JNJ-3989 200 mg SC injection Q4W from Day 1 (Week 1) to Week 44 + NA treatment (ETV 0.5 mg/TD 245 mg/TAF 25 mg) QD from Day 1 (Week 1) to Week 48. With separate consent, participants received optional treatment with PegIFN-alpha-2a 180 mcg SC injection QW after Week 40 liver biopsy for either 12 or 24 weeks (anytime between study Week 40 to 72) at investigator's discretion. At end of treatment Week 48, all participants entered follow-up and stopped JNJ-3989 and NA (if NA treatment completion criteria \[ALT \<3\*ULN, HBV DNA \<LLOQ; 20 IU/mL, HBeAg negative and HBsAg \<10 IU/mL\] was met based on Week 44 laboratory tests). If NA completion criteria were not met, NA was continued till FU phase end (study Week 96). Participants on PegIN-alpha2a and who had not met NA completion criteria at Week 48 were assessed at end of PegIN-alpha2a treatment and stopped NA, if completion criteria met and then entered FU phase. If NA-retreatment criteria (HBV DNA \>20,000 IU/mL, HBV DNA \>2,000 IU/mL but \<20,000 IU/mL and ALT \>5\*ULN) were met in FU phase, NA retreatment was started. | 4 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| FU Phase: Week 48 to Week 96 | Lost to Follow-up | 1 | 0 | 0 |
| FU Phase: Week 48 to Week 96 | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Panel 1 | Panel 2 | Panel 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 14.73 | 43.4 years STANDARD_DEVIATION 12.63 | 42 years STANDARD_DEVIATION 12.73 | 39 years STANDARD_DEVIATION 13.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 9 Participants | 4 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 3 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 4 Participants | 1 Participants | 5 Participants |
| Region of Enrollment BELGIUM | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment CANADA | 5 Participants | 0 Participants | 0 Participants | 5 Participants |
| Region of Enrollment FRANCE | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Region of Enrollment GERMANY | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment ITALY | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Region of Enrollment NEW ZEALAND | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Region of Enrollment POLAND | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment UNITED KINGDOM | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment UNITED STATES | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 10 | 0 / 10 | 0 / 4 |
| other Total, other adverse events | 9 / 10 | 10 / 10 | 3 / 4 | 5 / 10 | 6 / 10 | 3 / 4 |
| serious Total, serious adverse events | 1 / 10 | 0 / 10 | 0 / 4 | 0 / 10 | 0 / 10 | 0 / 4 |
Outcome results
Primary
Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40
Absolute change from baseline to on-treatment liver biopsy timepoint (Week 40) in terms of the percentage of HBsAg-positive hepatocytes (at Week 40) were reported.
Time frame: Baseline, Week 40
Population: Intent-to-treat (ITT) population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for Panels 1 and 2 alone.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Panel 1 | Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 | -78.46 percentage of HBsAg hepatocytes |
| Panel 2 | Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40 | -5.68 percentage of HBsAg hepatocytes |
Primary
Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12
Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 12 were reported.
Time frame: Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 | JNJ-73763976 (liver to plasma concentration) | 14.51 ratio | Standard Deviation 4.725 |
| Panel 1 | Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 | JNJ-73763924 (liver to plasma concentration) | 2844.26 ratio | Standard Deviation 1265.202 |
| Panel 1 | Panel 3: Correlation of Liver Concentration to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 12 | M65 to JNJ-73763976 (liver to liver concentration) | 19.47 ratio | Standard Deviation 3.267 |
Primary
Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40
Correlation of liver concentration to plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and liver concentration of JNJ-87719164 (M65: Deaminated metabolite of JNJ-73763976) to liver concentration JNJ-73763976 at Week 40 were reported.
Time frame: Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 | M65 to JNJ-73763976 (liver to liver concentration) | 22.65 ratio | Standard Deviation 1.407 |
| Panel 1 | Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 | JNJ-73763976 (liver to plasma concentration) | 12.67 ratio | Standard Deviation 7.269 |
| Panel 1 | Panel 3: Correlation of Liver to Plasma Concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) and Liver Concentration of JNJ-87719164 (M65: Deaminated Metabolite of JNJ-73763976) to Liver Concentration JNJ-73763976 at Week 40 | JNJ-73763924 (liver to plasma concentration) | 2847.66 ratio | Standard Deviation 1034.033 |
Primary
Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40
Liver concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 40 were reported.
Time frame: At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40 | JNJ-73763976 | 5883.33 ng/g | Standard Deviation 2147.145 |
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40 | JNJ-73763924 | 208666.67 ng/g | Standard Deviation 66860.551 |
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40 | M65 | 133800.00 ng/g | Standard Deviation 50615.413 |
Primary
Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12
Liver concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 - Molecules of JNJ-73763989 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 12 were reported.
Time frame: At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12 | JNJ-73763924 | 87300.00 nanograms per gram (ng/g) | Standard Deviation 31712.668 |
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12 | M65 | 66175.00 nanograms per gram (ng/g) | Standard Deviation 26000.817 |
| Panel 1 | Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12 | JNJ-73763976 | 3550.00 nanograms per gram (ng/g) | Standard Deviation 1674.714 |
Primary
Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12
Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 12 were reported.
Time frame: At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12 | JNJ-73763976 | 254.70 nanograms per milliliters (ng/mL) | Standard Deviation 123.841 |
| Panel 1 | Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12 | JNJ-73763924 | 36.18 nanograms per milliliters (ng/mL) | Standard Deviation 22.667 |
Primary
Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40
Plasma concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 40 were reported.
Time frame: At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Data for this outcome measure (OM) was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40 | JNJ-73763976 | 530.97 ng/mL | Standard Deviation 176.408 |
| Panel 1 | Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40 | JNJ-73763924 | 74.87 ng/mL | Standard Deviation 12.788 |
Secondary
Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination
Number of participants with clinically significant treatment-emergent abnormalities in physical examination were reported. Physical examination included head/neck/thyroid, eyes/ears/nose/throat, respiratory, cardiovascular, lymph nodes, abdomen, skin, musculoskeletal, and neurological examinations.
Time frame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 4 Participants |
| Panel 2 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 0 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 0 Participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 0 Participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 0 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination | 0 Participants |
Secondary
Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses
Number of participants with HBV-specific peripheral blood T-cell responses were reported. HBV-specific T-cells were characterized in peripheral blood mononuclear cell immune analysis by binding assays (multimer staining) combined with downstream T-cell responses and transcriptome profiling.
Time frame: Open-label: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24
Population: ITT population were analyzed. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure and n(number analyzed) signifies number of participants analyzed at specified categories. Here, n=0, signifies that no participants were available for the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 40 | 6 Participants |
| Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 44 | 0 Participants |
| Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 48 | 1 Participants |
| Panel 2 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 40 | 6 Participants |
| Panel 2 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 44 | 1 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Open Label: Week 40 | 0 Participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 24 | 5 Participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 2 | 4 Participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 12 | 1 Participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 2 | 10 Participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 12 | 5 Participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 24 | 9 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 2 | 3 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 24 | 4 Participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses | Follow-up Week 12 | 2 Participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance
Percentage of Participants who achieved HBeAg Seroclearance were reported. HBeAg seroclearance was defined as (quantitative\] HBeAg \<LLOQ (\<0.11 IU/mL); with HBeAg positive status at baseline and became HBeAg negative post-baseline.
Time frame: Follow-up Week 48
Population: ITT population: participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. N(Number of participants analyzed) = number of participants evaluable for this outcome measure. Data was not collected for Panel 2 participants as they were HBeAg negative at enrollment and thus did not fulfill planned analysis criteria (HBeAg positive status).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance | 37.5 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance | 50.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion
Percentage of participants who achieved HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as \[quantitative\] HBeAg \<LLOQ \[\<0.11 IU/mL\]; with HBeAg positive status at baseline and became HBeAg negative post-baseline) 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).
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population: participants randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. N' (number of participants analyzed) = participants evaluable for this outcome measure. Data was not collected for Panel 2 participants as they were HBeAg negative at enrollment and thus did not fulfill planned analysis criteria (HBeAg positive status).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion | 28.6 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion | 50.0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance
Percentage of Participants who achieved HBsAg Seroclearance were reported. HBsAg seroclearance was defined as quantitative HBsAg \<LLOQ (\<0.05 IU/mL).
Time frame: Follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance | 25.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance | 20.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance | 0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion
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 \[\>=5 mIU/mL\]).
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion | 28.6 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion | 11.1 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion | 0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment
Percentage of participants with HBsAg seroclearance (defined as HBsAg \< LLOQ: 0.05 IU/mL) at Week 72 without restarting NA treatment were reported.
Time frame: At Week 72 (24 weeks after completion of all study drugs at Week 48)
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment | 0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment | 1 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment | 0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares
Off-treatment (time period after stopping all study drugs \[including NA\]) biochemical flare was defined as first date of 2 consecutive visits with ALT and/or AST \>=3\*ULN and \>=3\*nadir (lowest value observed up to start of flare) while participant received no study drugs. End date of same off-treatment biochemical flare was defined as first date with 50 percentage (%) reduction from peak ALT and/or AST level & \<3\*ULN. On-treatment (time period during which the participant received any of study drugs) biochemical flare was defined as first date of 2 consecutive visits with ALT and/or AST \>=3\*ULN and \>=3\*nadir (lowest value observed up to start of flare) while participant was on-treatment. End date of same on-treatment biochemical flare was defined as first date with a 50% reduction from the peak ALT and/or AST level and \<3\*ULN, regardless of stopping study drugs. Participants were counted only once for any given flare, regardless of the number of times they actually experienced flare.
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here, n(number analyzed) signifies number of participants analyzed at specified categories and n=0 signifies that no participant was available for the analysis at the specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | On-treatment biochemical flare | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | Off-treatment biochemical flare | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | On-treatment biochemical flare | 10.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | Off-treatment biochemical flare | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares | On-treatment biochemical flare | 25.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares
Percentage of participants with off-treatment clinical flares were reported. Clinical flares occurred either when a virologic flare and biochemical flare overlapped in time or when a biochemical flare started within 4 weeks following the end of a virologic flare. Off-treatment was defined as the time period after stopping all study drugs (including NA). The start date of a clinical flare was the minimum start date of the virologic flare and biochemical flare. The end date of a clinical flare was the maximum end date of the virologic flare and biochemical flare, that is, the later date between HBV DNA returned to \<=200 IU/mL (or \<=1 log10) and 50 %reduction from the peak ALT and/or AST level and \<3\*ULN reached during the biochemical flare. Participants were counted only once for any given flare, regardless of the number of times they actually experienced the flare.
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population: participants randomly assigned/enrolled to an intervention arm and received at least 1 dose of drug. Participants were analyzed according to study drug randomly assigned/enrolled. N (Number of participants analyzed) = participants evaluable for this outcome measure. Data was not collected for Panel 1, as no participants met off-treatment criteria (set duration between last dose and last study visit) at final analysis and thus were not considered eligible for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >200 IU/mL | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >2,000 IU/mL | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >20,000 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >200 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >2,000 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares | HBV DNA >20,000 IU/mL | 50.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1
Virologic flare (VF) per derivation 1 was defined only for participants who were off-treatment (period after stopping all study drugs, including NA) and who had HBV DNA\<LLOQ (\<20 IU/mL) at last observed point on-treatment \[OT\]); start date of confirmed VF was first date of 2 consecutive visits with HBV DNA \>200 IU/mL. End date of same confirmed VF was first date when HBV DNA value returns to \<=200 IU/mL or date of NA restart, whichever comes first. Each virologic flare were categorized based on confirmed (that is, 2 consecutive values) peak HBV DNA above any of 3 thresholds within the start and end date of that flare as followed: 20,000 IU/mL, 2,000 IU/mL, and 200 IU/mL. Participants were counted only once for any given flare, regardless of the number of times they actually experienced the flare.
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population: participants randomly assigned or enrolled to an intervention arm and received at least 1 dose of drug. Participants were analyzed according to study drug randomly assigned/enrolled. N (Number of participants analyzed) = participants evaluable for this outcome measure. Data was not collected for Panel 1, as no participants met off-treatment criteria (set duration between last dose and last study visit) at final analysis and thus were not considered eligible for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 2,000 IU/mL | 33.3 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 20,000 IU/mL | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 200 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 200 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 2,000 IU/mL | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1 | HBV DNA > 20,000 IU/mL | 50.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48
Percentage of participants with sustained (reduction) serum HBsAg response per Definition 1 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 1 was defined as: for participants with data for last follow-up visit (Follow-up Week 48 for participants who did not receive PegIFN-alpha2a or received PegIFN-alpha2a and did not meet NA completion criteria, and last Follow-up visit for participants who received PegIFN-alpha2a and stopped NA during Follow-up): participants who had a \>1 log decline in HBsAg response at last scheduled follow-up visit and had an HBsAg \<1000 IU/mL at last scheduled follow-up visit, or for participants without data at last follow-up visit: HBsAg values had a \>2 log decline at second most recent visit or \>1.5 log decline at latest visit (most recent value used) compared to baseline and had an HBsAg \<1000 IU/mL at last available timepoint.
Time frame: Follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48 | 50.0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48 | 70.0 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48 | 50.0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48
Percentage of participants with sustained (reduction) serum HBsAg response per Definition 2 at follow-up Week 48 were reported. Sustained serum 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 log HBsAg at 2 of 3 last visit and 1 of 3 last visit is \<0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is \<0.2.
Time frame: Follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48 | 50.0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48 | 42.9 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48 | 50.0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48
Percentage of participants with sustained (reduction) serum HBsAg response per Definition 3 at follow-up Week 48 were reported. Sustained serum HBsAg response per definition 3 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 log HBsAg at 2 of 3 last visit and 1 of 3 last visit is \<0.2, and the difference between log HBsAg at 3 of 3 last visit and 1 of 3 last visit is \<0.2 and have an HBsAg \<1000 IU/mL at the last available timepoint.
Time frame: From follow-up Week 24 up to follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48 | 25.0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48 | 42.9 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48 | 50.0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48
Percentage of participants with sustained (reduction) serum HBsAg response per definition 4 follow-up Week 48 were reported. Sustained serum HBsAg response per definition 4 were classified into 3 categories with respect to the difference between HBsAg level at the last Follow-up timepoint and end of treatment: Increase: \>+0.2 log10 IU/mL , stable: within plus or minus (+/-) 0.2 log10 IU/mL, and decrease: \>-0.2 log10 IU/mL.
Time frame: Follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Decrease: > -0.2 log10 IU/mL | 22.2 Percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Stable: Within +/-0.2 log10 | 11.1 Percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Increase: > +0.2 log10 IU/mL | 66.7 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Decrease: > -0.2 log10 IU/mL | 30.0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Stable: Within +/-0.2 log10 | 0 Percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Increase: > +0.2 log10 IU/mL | 70.0 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Stable: Within +/-0.2 log10 | 0 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Increase: > +0.2 log10 IU/mL | 75.0 Percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48 | Decrease: > -0.2 log10 IU/mL | 25.0 Percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Percentage of participants with TEAES (including serious and non-serious) and TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Any AE occurring at or after the initial administration of study intervention was considered to be treatment emergent. 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.
Time frame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 10.0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 90.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 100.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 75.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 50.0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 60.0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 75.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough
Percentage of participants with virologic breakthrough on treatment were reported. Virological breakthrough was defined as having a 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 (\<20 IU/mL) of the HBV DNA assay. Confirmed HBV DNA increase/level means that the criterion should be fulfilled at 2 or more consecutive time points or at the last observed on-treatment time point. On treatment was defined as the time period in which the participant received any of the study interventions (JNJ-3989 and/or JNJ 6379 and/or NA and/or PegIFN-alpha2a).
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough | 0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)
ECG parameters included ECG mean heart rate (HR)(beats per minute\[bpm\]), Pulse rate (PR) interval (milliseconds \[ms\]), QRS duration (ms) and QTc Corrected (Fridericia's formula QTcF). Abnormalities were graded as follows: ECG mean heart rate (abnormally low HR \<45 bpm) and (abnormally high HR\>=120 bpm); PR interval (abnormally high \>220 ms) and QPRS (abnormally high \>=120 ms); OT interval corrected for heart rate according to Fridericia (QTcF); borderline prolonged (BRD Pr )QTc (\>=450 to \<=480 ms), prolonged QTc (\>=480 to \<=500 ms)and pathologically prolonged QTc (\>500 ms). For worst abnormality, treatment-emergent was concluded if the abnormality worsened as compared to the abnormality at baseline: abnormally high to abnormally low and vice-versa. Only those abnormality categories in which at least one participant had data were reported.
Time frame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 11.1 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 20.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 10.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 11.1 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 20.0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 10.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | QTcF Interval: Aggregate: borderline prolonged QT (>=450to<=480 ms) | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | ECG Mean HR: low (<45 bpm) | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG) | PR Interval: Aggregate: Abnormally high (>220 ms) | 0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs
Percentage of participants with worst treatment-emergent DAIDS toxicity grade in vital signs were reported. Abnormality grades were: pulse rate (abnormally low \<=45 bpm) and (abnormally high \>=120 bpm). An assessment was treatment-emergent if abnormality worsened as compared to the abnormality at baseline: from abnormally high to abnormally low and vice-versa. Only the category (pulse rate) in which at least one participant had data were reported.
Time frame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here N (Number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 10.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs | 0 percentage of participants |
Secondary
Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests
Clinical laboratory test parameters were Hematology : absolute neutrophil count (ANC); Chemistry : alanine aminotransferase (ALT) and serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase(AST) or serum glutamic oxaloacetic transaminase (SGOT), amylase (pancreatic and total), creatinine Kinase, creatinine, low-density lipoprotein (LDL), lipase, estimated glomerular filtration rate (eGFR) on serum creatinine (Cr). DAIDS toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). Percentage of participants with treatment-emergent DAIDS toxicity Grade 3 or 4 were reported in this outcome measure. For toxicity grades, treatment-emergent was concluded if the postbaseline grade was worse than the baseline grade. Only those abnormality categories in which at least one participant had data were reported.
Time frame: Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here n (number analyzed) signifies number of participants analyzed at specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 11.1 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 11.1 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 25.0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 0 percentage of participants |
| Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 10.0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 0 percentage of participants |
| Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 10.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 25.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 25.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 25.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 10.0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 1 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 10.0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 10.0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 2 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 4 | 25.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: ALT or SGPT: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: LDL (Fasting): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: eGFR Cr: Low: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Hematology: Absolute Neutrophil Count: Low: Grade 3 | 25.0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Creatinine Kinase : High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Lipase: High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Pancreatic): High: Grade 4 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: Amylase (Total): High: Grade 3 | 0 percentage of participants |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Percentage of Participants With Worst (Grade 3 and 4) Treatment-emergent Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity Grade in Clinical Laboratory Tests | Chemistry: AST/SGOT: High: Grade 3 | 25.0 percentage of participants |
Secondary
Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance
Time to first occurrence of HBsAg seroclearance (defined as quantitative HBsAg \<LLOQ \[\<0.05 IU/mL\]) were reported. Time to first occurrence of 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 the HBsAg seroclearance. Participants who withdrew early from the study before achieving HBsAg seroclearance or who did not achieve HBsAg seroclearance were censored at the last available HBsAg assessment. Kaplan-Meier method was used for the estimation.
Time frame: From baseline (Day 1) up to follow-up Week 48
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance | NA weeks |
| Panel 2 | Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance | NA weeks |
| FU Phase: Panel 3 | Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance | NA weeks |
Secondary
Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40
Change from baseline in percentage of intrahepatic viral parameter: silent infected hepatocytes (that is infected hepatocytes without HBV transcription; cccDNA-positive/HBV RNA-negative hepatocytes) at Week 40 were reported. The percentage of silent infected hepatocytes (SIH), were derived as number of silent infected hepatocytes\*100 per total number of evaluated hepatocytes.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40 | 25.06 percent change in SIH |
| Panel 2 | Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40 | 2.88 percent change in SIH |
Secondary
Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40
Change from baseline in percentage of intrahepatic viral parameter: cccDNA positive hepatocytes were reported. The percentage of cccDNA-positive hepatocytes, were derived as number of cccDNA positive hepatocytes\*100 per total number of evaluated hepatocytes.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40 | -4.50 percent change in cccDNA+ hepatocytes |
| Panel 2 | Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40 | -2.40 percent change in cccDNA+ hepatocytes |
Secondary
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40
Change from baseline in percentage of intrahepatic viral parameter: HBsAg positive hepatocytes at Week 40 were reported. The percentage of HBsAg positive hepatocytes were derived as number of HBsAg positive hepatocytes \* 100 per total number of evaluated hepatocytes.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm andreceived at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40 | -92.38 percent change in HBsAg+ hepatocytes |
| Panel 2 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40 | -14.19 percent change in HBsAg+ hepatocytes |
Secondary
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40
Change from baseline in percentage of intrahepatic viral parameter: HBcAg positive hepatocytes at Week 40 were reported. The percentage of HBcAg positive hepatocytes were derived as number of HBcAg positive hepatocytes\*100 per total number of evaluated hepatocytes.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this OM was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40 | -54.49 percent change in HBcAg+ Hepatocytes |
| Panel 2 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40 | 0.03 percent change in HBcAg+ Hepatocytes |
Secondary
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40
Change from baseline in percentage of intrahepatic viral Parameter: pgRNA positive hepatocytes at Week 40 were reported. The percentage of pgRNA-positive hepatocytes, were derived as number of pgRNA positive hepatocytes\*100 per total number of evaluated hepatocytes.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this OM was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40 | -81.23 percent change in pgRNA+ hepatocytes |
| Panel 2 | Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40 | -6.74 percent change in pgRNA+ hepatocytes |
Secondary
Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40
Change from baseline in transcriptional activity (ratio of pgRNA/cccDNA) at Week 40 were reported.
Time frame: Baseline, Week 40
Population: ITT population included participants who were randomly assigned or enrolled to an intervention arm and received at least 1 dose of intervention. Participants were analyzed according to study intervention they were randomly assigned or enrolled. Here N (Number of participants analyzed) signifies the number of participants that were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Panel 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel 1 | Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40 | 50.00 ratio |
| Panel 2 | Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40 | 8.86 ratio |
Secondary
Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Minimum observed plasma concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmin of JNJ-73763989 and its molecules
Time frame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: A pharmacokinetics (PK) analysis which included participants of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Data for this outcome measure was planned to be collected and analyzed for Panel 2 and 3 alone.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Panel 1 | Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | NA nanograms per milliliter (ng/mL) |
| Panel 1 | Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | NA nanograms per milliliter (ng/mL) |
| Panel 2 | Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | NA nanograms per milliliter (ng/mL) |
| Panel 2 | Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | NA nanograms per milliliter (ng/mL) |
Secondary
Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Plasma trough concentration (C\[0hour\]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. C0h was the pre-dose plasma concentration of the JNJ-73763989 (JNJ-73763976, JNJ-73763924). Non-compartmental analysis were conducted to analyze plasma concentration of JNJ-73763989 and its molecules.
Time frame: Week 4 : Pre-dose on Day 29
Population: A pharmacokinetics (PK) analysis which included participants of Panel 2 and Panel 3 who had consented to participate in the intensive PK subgroup were analyzed. Data for this outcome measure was planned to be collected and analyzed for Panel 2 and 3 alone.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Panel 1 | Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | NA nanograms per milliliter (ng/mL) |
| Panel 1 | Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | NA nanograms per milliliter (ng/mL) |
| Panel 2 | Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | NA nanograms per milliliter (ng/mL) |
| Panel 2 | Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | NA nanograms per milliliter (ng/mL) |
Secondary
Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze AUC0 to 24h of JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: Pharmacokinetics (PK) analysis included Panel 2 participants who had consented to participate in intensive PK subgroup. N (Number of participants analyzed) = participants who were evaluable for this outcome measure. n(number analyzed) = number of participants analyzed at specified categories. As planned, summary analysis was performed when overall number of participants analyzed were \>=3 and thus participant wise data were reported for Panel 2 alone in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 - Participant 1 | 27744 nanograms*hour per milliliters (ng*h/mL) |
| Panel 1 | Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 - Participant 2 | 13820 nanograms*hour per milliliters (ng*h/mL) |
| Panel 1 | Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 - Participant 1 | 5388 nanograms*hour per milliliters (ng*h/mL) |
| Panel 1 | Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 - Participant 2 | 2649 nanograms*hour per milliliters (ng*h/mL) |
Secondary
Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Maximum observed plasma concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: Pharmacokinetics (PK) analysis included Panel 2 participants who had consented to participate in intensive PK subgroup. N (Number of participants analyzed) = participants who were evaluable for this outcome measure. n(number analyzed) = number of participants analyzed at specified categories. As planned, summary analysis was performed when overall number of participants analyzed were \>=3 and thus participant wise data were reported for Panel 2 alone in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 - Participant 1 | 2757 nanograms per milliliter (ng/mL) |
| Panel 1 | Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 - Participant 2 | 1062 nanograms per milliliter (ng/mL) |
| Panel 1 | Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 - Participant 1 | 595 nanograms per milliliter (ng/mL) |
| Panel 1 | Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 - Participant 2 | 205 nanograms per milliliter (ng/mL) |
Secondary
Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924)
Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
Population: Pharmacokinetics (PK) analysis included Panel 2 participants who had consented to participate in intensive PK subgroup. N (Number of participants analyzed) = participants who were evaluable for this outcome measure. n(number analyzed) = number of participants analyzed at specified categories. As planned, summary analysis was performed when overall number of participants analyzed were \>=3 and thus participant wise data were reported for Panel 2 alone in this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panel 1 | Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) | JNJ-73763976 - Participant 1 | 6.00 hours |
| Panel 1 | Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) | JNJ-73763976 - Participant 2 | 10.00 hours |
| Panel 1 | Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) | JNJ-73763924 - Participant 1 | 6.00 hours |
| Panel 1 | Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924) | JNJ-73763924 - Participant 2 | 10.00 hours |
Secondary
Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze AUC0 to 24h of JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: A pharmacokinetics (PK) analysis which included participants of Panel 3 who had consented to participate in the intensive PK subgroup. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Panel 1 | Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | 13,256 nanograms*hour per milliliters (ng*h/mL) |
| Panel 1 | Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | 2,394 nanograms*hour per milliliters (ng*h/mL) |
Secondary
Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Maximum observed plasma concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Population: Pharmacokinetics (PK) analysis which included Panel 3 participants who had consented to participate in the intensive PK subgroup. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel 1 | Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | 924 nanograms per milliliter (ng/mL) | Standard Deviation 428 |
| Panel 1 | Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | 178 nanograms per milliliter (ng/mL) | Standard Deviation 73.1 |
Secondary
Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules.
Time frame: Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
Population: Pharmacokinetics (PK) analysis which included Panel 3 participants who had consented to participate in the intensive PK subgroup. Data for this outcome measure was planned to be collected and analyzed for Panel 3 alone.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Panel 1 | Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763976 | 6.00 hours |
| Panel 1 | Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924) | JNJ-73763924 | 5.04 hours |