A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (INSIGHT)

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: JNJ-73763989; Drug: JNJ-56136379; Drug: Entecavir (ETV); Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide (TAF); Drug: PegIFN-alpha-2a (Optional)

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 2C4
      • Toronto General Hospital
• France
  • Clichy, France, 92110
    • Hôpital Beaujon
• Germany
  • Hamburg, Germany, D-20246
    • University Medical Center
• Italy
  • Milano, Italy, 20122
    • Irccs Ospedale Maggiore Di Milano
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research
• Poland
  • Myslowice, Poland, 41-400
    • ID Clinic
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit
  • London, United Kingdom, SE5 9RF
    • Kings College Hospital
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: JNJ-73763989; JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.; Drug: JNJ-56136379; JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.; Drug: Entecavir (ETV); ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir disoproxil; Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir alafenamide (TAF); TAF will be administered orally once daily up to 48 weeks as NA treatment.; Drug: PegIFN-alpha-2a (Optional); PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.
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.	Drug: JNJ-73763989; JNJ-73763989 will be administered subcutaneously once every 4 weeks up to Week 44.; Drug: JNJ-56136379; JNJ-56136379 tablets will be administered orally once daily up to 48 weeks.; Drug: Entecavir (ETV); ETV tablet will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir disoproxil; Tenofovir disoproxil will be administered orally once daily up to 48 weeks as NA treatment.; Drug: Tenofovir alafenamide (TAF); TAF will be administered orally once daily up to 48 weeks as NA treatment.; Drug: PegIFN-alpha-2a (Optional); PegIFN-alpha-2a injection will be administered subcutaneously once weekly after Week 40 for either 12 or 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 40
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.	At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
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.	At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
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.	At Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
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.	At Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
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.	Week 12 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)
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.	Week 40 (at the time of liver biopsy: 24 hours post dose of JNJ-73763989)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Follow-up Week 48
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).	Follow-up Week 48
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.	Follow-up Week 48
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.	Baseline, Week 40
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.	Baseline, Week 40
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.	Baseline, Week 40
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.	Baseline, Week 40
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.	Baseline, Week 40
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.	Baseline, Week 40
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.	At Week 72 (24 weeks after completion of all study drugs at Week 48)
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.	Follow-up Week 48
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.	From follow-up Week 24 up to follow-up Week 48
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.	Follow-up Week 48
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]).	From baseline (Day 1) up to follow-up Week 48
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).	From baseline (Day 1) up to follow-up Week 48
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.	From baseline (Day 1) up to follow-up Week 48
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.	From baseline (Day 1) up to follow-up Week 48
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.	From baseline (Day 1) up to follow-up Week 48
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.	From baseline (Day 1) up to follow-up Week 48
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).	From baseline (Day 1) up to follow-up Week 48
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.	Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
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.	Open-label: Weeks 40, 44, and 48; Follow-up Phase: Follow-up Weeks 2, 12 and 24
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.	Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
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.	Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
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.	Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
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.	Open-label: Day 1 (Week 1) up to Week 48; Follow-up Phase: Follow-up Week 1 up to follow-up Week 48
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.	Week 4 : Pre-dose on Day 29
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.	Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
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.	Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
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	Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
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.	Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
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.	Week 4 (Day 29): Post dose (15 minutes, 30 minutes, 1, 2, 3, 4, 6, and 24 hours)
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.	Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose
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.	Week 4 (Day 29): Pre-dose and 15 minutes, 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2021
• Primary Completion (Actual): February 8, 2023
• Study Completion (Actual): January 9, 2024

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Virus Diseases; Herpesviridae Infections; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; JNJ-56136379; Peginterferon alfa-2a; Entecavir
• Other Study ID Numbers: CR108790; 2019-004475-39 (EudraCT Number); 73763989HPB2003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No