Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04585789




Registration number
NCT04585789
Ethics application status
Date submitted
9/10/2020
Date registered
14/10/2020
Date last updated
21/05/2025

Titles & IDs
Public title
A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection
Scientific title
A Phase 2 Randomized, Open-label, Parallel-group, Multicenter Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Response to Combination Regimens Containing JNJ-73763989 and Nucleos(t)Ide Analog With or Without JNJ-56136379 in Patients With Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
73763989HPB2003
Secondary ID [2] 0 0
CR108790
Universal Trial Number (UTN)
Trial acronym
INSIGHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNJ-73763989
Treatment: Drugs - JNJ-56136379
Treatment: Drugs - Entecavir (ETV)
Treatment: Drugs - Tenofovir disoproxil
Treatment: Drugs - Tenofovir alafenamide (TAF)
Treatment: Drugs - PegIFN-alpha-2a (Optional)

Experimental: Panel 1: JNJ-73763989+ NA - Ongoing and new participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (last injection at Week 44) and nucleos(t)ide analog (NA) treatment (either entecavir \[ETV\], tenofovir disoproxil or tenofovir alafenamide \[TAF\] tablets) once daily up to 48 weeks. Participants may receive optional treatment with pegylated interferon alpha-2a (PegIFN-alpha-2a) after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.

Experimental: Panel 2: JNJ-73763989+ NA - Ongoing and new participants will receive JNJ-73763989 SC injection once every 4 weeks (last injection at Week 44) and NA treatment (ETV, tenofovir disoproxil or TAF tablets) once daily up to 48 weeks. Participants may receive optional treatment with PegIFN-alpha-2a after the Week 40 for a duration of either 12 or 24 weeks at the investigator's discretion. As per amendment-5, JNJ-56136379 is no longer included as part of the study intervention and all participants are counted as single arm in each panel.


Treatment: Drugs: JNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.

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

Treatment: Drugs: Entecavir (ETV)
ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: Tenofovir disoproxil
Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: Tenofovir alafenamide (TAF)
TAF will be administered orally once daily up to 48 weeks as NA treatment.

Treatment: Drugs: PegIFN-alpha-2a (Optional)
PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Panel 1 and 2: Absolute Change From Baseline in the Percentage of Hepatitis B Surface Antigen (HBsAg) Hepatocytes at Week 40
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 40
Primary outcome [2] 0 0
Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 12
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Primary outcome [3] 0 0
Panel 3: Liver Concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 [M65; Deaminated Metabolite of JNJ-73763976]) at Week 40
Assessment method [3] 0 0
Liver concentrations of JNJ-73763989 (JNJ-73763976, and JNJ-73763924 and JNJ-87719164 \[M65; deaminated metabolite of JNJ-73763976\]) at Week 40 were reported.
Timepoint [3] 0 0
At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Primary outcome [4] 0 0
Panel 3: Plasma Concentration of JNJ-73763989 (JNJ-73763976, and JNJ-73763924) at Week 12
Assessment method [4] 0 0
Plasma concentration of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 12 were reported.
Timepoint [4] 0 0
At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Primary outcome [5] 0 0
Panel 3: Plasma Concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924) at Week 40
Assessment method [5] 0 0
Plasma concentrations of JNJ-73763989 (JNJ-73763976 and JNJ-73763924-molecules of JNJ-73763989) at Week 40 were reported.
Timepoint [5] 0 0
At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Primary outcome [6] 0 0
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
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Primary outcome [7] 0 0
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
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
Secondary outcome [1] 0 0
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 2 at Follow-up Week 48
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Follow-up Week 48
Secondary outcome [2] 0 0
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroclearance
Assessment method [2] 0 0
Percentage of Participants who achieved HBsAg Seroclearance were reported. HBsAg seroclearance was defined as quantitative HBsAg \
Timepoint [2] 0 0
Follow-up Week 48
Secondary outcome [3] 0 0
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroclearance
Assessment method [3] 0 0
Percentage of Participants who achieved HBeAg Seroclearance were reported. HBeAg seroclearance was defined as (quantitative\] HBeAg \
Timepoint [3] 0 0
Follow-up Week 48
Secondary outcome [4] 0 0
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Hepatitis B Core Antigen Positive (HBcAg+) Hepatocytes at Week 40
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Week 40
Secondary outcome [5] 0 0
Panel 1,and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Covalently Closed Circular Deoxyribonucleic Acid Positive (cccDNA+) Hepatocytes at Week 40
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Baseline, Week 40
Secondary outcome [6] 0 0
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: HBsAg Positive (HBsAg+) Hepatocytes at Week 40
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Baseline, Week 40
Secondary outcome [7] 0 0
Panel 1 and 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Pre-genomic Ribonucleic Acid Positive (pgRNA+) Hepatocytes at Week 40
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Baseline, Week 40
Secondary outcome [8] 0 0
Panel 1 and 2: Change From Baseline in Transcriptional Activity (Ratio of pg RNA/cccDNA) at Week 40
Assessment method [8] 0 0
Change from baseline in transcriptional activity (ratio of pgRNA/cccDNA) at Week 40 were reported.
Timepoint [8] 0 0
Baseline, Week 40
Secondary outcome [9] 0 0
Panel 1, 2: Change From Baseline in Percentage of Intrahepatic Viral Parameter: Silent Infected Hepatocytes at Week 40
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
Baseline, Week 40
Secondary outcome [10] 0 0
Panel 1, 2 and 3: Percentage of Participants With HBsAg Seroclearance at Week 72 Without Restarting Nucleos(t)Ide Analog (NA) Treatment
Assessment method [10] 0 0
Percentage of participants with HBsAg seroclearance (defined as HBsAg \< LLOQ: 0.05 IU/mL) at Week 72 without restarting NA treatment were reported.
Timepoint [10] 0 0
At Week 72 (24 weeks after completion of all study drugs at Week 48)
Secondary outcome [11] 0 0
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 1 at Follow-up Week 48
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Follow-up Week 48
Secondary outcome [12] 0 0
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 3 at Follow-up Week 48
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
From follow-up Week 24 up to follow-up Week 48
Secondary outcome [13] 0 0
Panel 1, 2 and 3: Percentage of Participants With Sustained (Reduction) Serum HBsAg Response Per Definition 4 at Follow-up Week 48
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
Follow-up Week 48
Secondary outcome [14] 0 0
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBsAg Seroconversion
Assessment method [14] 0 0
Seroconversion of HBsAg was defined as having achieved HBsAg seroclearance (defined as quantitative HBsAg \=LLOQ \[\>=5 mIU/mL\]).
Timepoint [14] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [15] 0 0
Panel 1, 2 and 3: Percentage of Participants Who Achieved HBeAg Seroconversion
Assessment method [15] 0 0
Percentage of participants who achieved HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as \[quantitative\] HBeAg \
Timepoint [15] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [16] 0 0
Panel 1, 2 and 3: Percentage of Participants With Off-treatment Virologic Flares Per Derivation 1
Assessment method [16] 0 0
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\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.
Timepoint [16] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [17] 0 0
Panel 1, 2 and 3: Percentage of Participants With Off-treatment and On-treatment Biochemical Flares
Assessment method [17] 0 0
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.
Timepoint [17] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [18] 0 0
Panel 1, 2 and 3: Percentage of Participants With Off-treatment Clinical Flares
Assessment method [18] 0 0
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.
Timepoint [18] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [19] 0 0
Panel 1, 2 and 3: Time to First Occurence of HBsAg Seroclearance
Assessment method [19] 0 0
Time to first occurrence of HBsAg seroclearance (defined as quantitative HBsAg \
Timepoint [19] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [20] 0 0
Panel 1, 2 and 3: Percentage of Participants With Virologic Breakthrough
Assessment method [20] 0 0
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 \
Timepoint [20] 0 0
From baseline (Day 1) up to follow-up Week 48
Secondary outcome [21] 0 0
Panel 1, 2 and 3: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Assessment method [21] 0 0
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.
Timepoint [21] 0 0
Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Secondary outcome [22] 0 0
Panel 1, 2 and 3: Number of Participants With HBV-Specific Peripheral Blood T-cell Responses
Assessment method [22] 0 0
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.
Timepoint [22] 0 0
Open-label: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24
Secondary outcome [23] 0 0
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
Assessment method [23] 0 0
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.
Timepoint [23] 0 0
Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Secondary outcome [24] 0 0
Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High)Treatment-emergent DAIDS Toxicity Grade in Electrocardiogram (ECG)
Assessment method [24] 0 0
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.
Timepoint [24] 0 0
Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Secondary outcome [25] 0 0
Panel 1, 2 and 3: Percentage of Participants With Worst (Abnormally Low/High) Treatment-emergent DAIDS Toxicity Grade in Vital Signs
Assessment method [25] 0 0
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.
Timepoint [25] 0 0
Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Secondary outcome [26] 0 0
Panel 1, 2 and 3: Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Physical Examination
Assessment method [26] 0 0
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.
Timepoint [26] 0 0
Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
Secondary outcome [27] 0 0
Panel 2 and 3: Plasma Trough Concentration (C[0hour]) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [27] 0 0
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.
Timepoint [27] 0 0
Week 4 : Pre-dose on Day 29
Secondary outcome [28] 0 0
Panel 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [28] 0 0
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.
Timepoint [28] 0 0
Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Secondary outcome [29] 0 0
Panel 3: Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [29] 0 0
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.
Timepoint [29] 0 0
Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Secondary outcome [30] 0 0
Panel 2 and 3: Minimum Observed Plasma Concentration (Cmin) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [30] 0 0
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
Timepoint [30] 0 0
Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Secondary outcome [31] 0 0
Panel 2: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976,JNJ-73763924)
Assessment method [31] 0 0
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.
Timepoint [31] 0 0
Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
Secondary outcome [32] 0 0
Panel 3:Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [32] 0 0
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.
Timepoint [32] 0 0
Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
Secondary outcome [33] 0 0
Panel 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [33] 0 0
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.
Timepoint [33] 0 0
Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
Secondary outcome [34] 0 0
Panel 3: Area Under the Plasma Concentration-time Curve From Time Zero to 24hours (AUC0 to 24h) of JNJ-73763989 (JNJ-73763976, JNJ-73763924)
Assessment method [34] 0 0
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.
Timepoint [34] 0 0
Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/01/2024
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
Belgium
State/province [2] 0 0
Edegem
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
France
State/province [4] 0 0
Clichy
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Italy
State/province [6] 0 0
Milano
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
Poland
State/province [8] 0 0
Myslowice
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04585789