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

A Phase 2, Randomized, Open-label, Multicenter Study to Evaluate Efficacy, Pharmacokinetics, Safety, and Tolerability of Treatment With JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog With or Without JNJ-56136379 in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B Virus Infection

The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: JNJ-73763989; Drug: PegIFN-alpha-2a; Drug: Tenofovir disoproxil; Drug: Tenofovir alafenamide; Drug: JNJ-56136379

Detailed Description

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations. The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment 6 of the study.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University Of Calgary
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute (G.I.R.I.)
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Vancouver ID Research and Care Centre Society
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 2C4
      • Toronto General Hospital
• France
  • Clichy, France, 92110
    • Hopital Beaujon
  • Grenoble, France, 38043
    • CHU de Grenoble Hopital Albert Michallon
  • Lyon, France, 69004
    • Hôpital de la Croix Rousse
  • Nantes, France, 44093
    • CHU NANTES - Hôtel Dieu
  • Paris, France, 75012
    • CHU Hôpital Saint Antoine
  • Rennes, France, 35033
    • Chu Rennes Hopital Pontchaillou
  • Vandoeuvre les Nancy, France, 54511
    • CHU Nancy Brabois
• Germany
  • Berlin, Germany, 10439
    • Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany, 60590
    • Universitätsklinikum Johann Wolfgang Goethe- Universität Frankfurt Medizinische Klinik 1
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• Japan
  • Hiroshima shi, Japan, 734 8551
    • Hiroshima University Hospital
  • Kashihara, Japan, 634-8522
    • Nara Medical University Hospital
  • Musashino, Japan, 180-8610
    • Musashino Red Cross Hospital
  • Nagoya, Japan, 467 8602
    • Nagoya City University Hospital
  • Yokohama, Japan, 232 0024
    • Yokohama City University Medical Center
• Russian Federation
  • Irkutsk, Russian Federation, 664003
    • Irkutsk State Medical University
  • Kazan, Russian Federation, 420140
    • Republic Clinical Infectious Hospital n.a. AF Agafonov
  • Saint Petersburg, Russian Federation, 190103
    • St. Petersburg City Center for AIDS and Infectious Diseases Treatment and Prophylaxis
  • Saint-Petersburg, Russian Federation, 195067
    • Clinical Infectious Diseases Hospital n. a. S.P. Botkin
  • Samara, Russian Federation, 443045
    • Medical Company Hepatolog Ltd
  • Smolensk, Russian Federation, 214018
    • Smolensk Regional Clinical Hospital
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical University
• Spain
  • Barcelona, Spain, 8028
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe University Hospital
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34764
    • Ümraniye Training and Research Hospital
  • Izmir, Turkey, 35100
    • Ege University Medical of Faculty, Department of Gastroenterology
  • Kucukcekmece, Turkey, 34303
    • Acibadem Mehmet Ali Aydinlar University
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • NHS Greater Glasgow and Clyde - Gartnavel General Hospital
  • Glasgow, United Kingdom, G31 2ER
    • Glasgow Royal Infirmary
  • London, United Kingdom, E1 1BB
    • Grahame Hayton Unit
  • London, United Kingdom, SE5 9RF
    • Kings College Hospital
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Center for Liver Diseases
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
• Currently not treated chronic hepatitis B virus (HBV) infection with alanine transaminase (ALT) less than (<) 2* upper limit of normal (ULN) at screening and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)
• Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
• Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 9 Kilopascal (kPa) at 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 or symptoms of hepatic decompensation, including but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal varices
• Evidence of liver disease of non-HBV etiology
• Participants with a history of malignancy within 5 years before screening
• Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
• Contraindications to the use of PegIFN-α2a

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Participants Enrolled Prior to Protocol Amendment 5 is in Effect; During the Induction phase, participants will receive JNJ-73763989 subcutaneously along with JNJ-56136379 tablet orally with NA (either tenofovir disoproxil or tenofovir alafenamide tablets orally) treatment. At the start of consolidation phase, participants will be randomized to receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and JNJ-56136379 with NA in arm 1 and arm 2 (without PegIFN-alpha-2a). According to predefined criteria NA treatment may be continued during the follow up (FU) phase.	Drug: JNJ-73763989; JNJ-73763989 injection will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PegIFN-alpha-2a; PegIFN-alpha-2a injection will be administered subcutaneously.; Drug: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.; Drug: Tenofovir alafenamide; Tenofovir alafenamide film-coated tablet will be administered orally.; Drug: JNJ-56136379; JNJ-56136379 will be administered orally.; Other Names: JNJ-6379
Experimental: Cohort 2: Participants Enrolled After Protocol Amendment 5 is in Effect; Following implementation of protocol amendment- 5 and 6, all participants will receive JNJ-73763989 subcutaneously along with NA (tenofovir disoproxil tablets orally) for 36 weeks (induction phase). In the consolidation phase, participants will receive PegIFN-alpha-2a subcutaneously in addition to JNJ-73763989 and NA for 12 weeks. According to predefined criteria NA treatment may be continued during the follow up (FU) phase. JNJ-56136379 (JNJ-6379) was discontinued as per amendment 6 of the study.	Drug: JNJ-73763989; JNJ-73763989 injection will be administered subcutaneously.; Other Names: JNJ-3989; Drug: PegIFN-alpha-2a; PegIFN-alpha-2a injection will be administered subcutaneously.; Drug: Tenofovir disoproxil; Tenofovir disoproxil film-coated tablet will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Functional Cure: Hepatitis B Surface Antigen (HBsAg) Seroclearance at 24 Weeks After Stopping All Study Interventions at the End of Consolidation Phase (CP) and Without Restarting Nucleos(t)Ide Analog (NA) Treatment	Percentage of participants with functional cure (defined as percentage of participants with HBsAg seroclearance at 24 weeks after stopping all study interventions at the end of consolidation phase and without restarting NA treatment) were reported. Seroclearance HBsAg was defined as a (quantitative) HBsAg level <lower limit of quantification (LLOQ; <0.05 international units per milliliter [IU/mL]).	At follow-up (FU) phase Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the study intervention. Treatment-emergent AEs are all AEs with an onset on or after the first administration of study treatment or any ongoing event that worsened in severity, intensity or frequency after the first administration of study treatment.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)	Number of participants with TESAEs were reported. was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the study intervention. Treatment-emergent AEs are all AEs with an onset on or after the first administration of study treatment or any ongoing event that worsened in severity, intensity or frequency after the first administration of study treatment. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Number of Participants With Worst (Grade 3 or 4) Treatment-emergent DAIDS Toxicity Grade in Clinical Laboratory Tests	Clinical laboratory test parameters were Hematology: absolute lymphocyte count, absolute neutrophil count (ANC), hemoglobin, Neutrophils Band Form, Neutrophils segmented, white blood cells (WBC) decreased, ; Chemistry: alanine aminotransferase (ALT) & serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase (SGOT), cholesterol (fasting), creatinine Kinase, creatinine, GFR from Creatinine Adjusted for BSA, GFR from Cystatin C Adjusted for BSA, low-density lipoprotein (LDL), triglycerides (fasting); Urinalysis: glycosuria. DAIDS toxicity grades: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). Number of participants with treatment-emergent DAIDS toxicity Grade 3 or 4 were reported in this outcome measure.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Number of Participants With Worst Treatment-emergent Abnormality in Electrocardiogram (ECGs)	Number of participants with worst treatment-emergent abnormality in ECG were reported. Treatment-emergent abnormality was defined as the abnormalities that were worsened as compared to the abnormality at baseline; which also included the shift from abnormally high to abnormally low and vice-versa. ECG parameters included heart rate (HR; abnormally low, HR <45 beats per minute (bpm) and (abnormally high HR>=120 bpm; PR interval abnormally high >220 milliseconds (ms): QRS interval abnormally high >=120 ms; QT corrected (Fridericia QTcF) categories; borderline prolonged QTc interval <450 to <=480 ms), prolonged QTc interval <480 to <=500 ms) and pathologically prolonged QTc interval >500 ms).	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Number of Participants With Worst Treatment-emergent Abnormalities in Vital Signs	Number of participants with worst treatment-emergent abnormalities in vital signs were reported. Treatment-emergent abnormality was defined as the abnormalities that were worsened as compared to the abnormality at baseline; which also included the shift from abnormally high to abnormally low and vice-versa. Abnormalities in vital signs included abnormal pulse rate (PR); abnormally low, <=45 bpm and abnormally high >=120 bpm; diastolic blood pressure (DBP) abnormally low <=50 mmHg, systolic blood pressure (SBP) abnormally low <=90 mmHg. Additionally, abnormal low SBP and DBP were <=50 mmHg and <+90 mmHg. Only those categories in which at least one participant had data were reported.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Number of Participants With Clinically Important Abnormalities in Physical Examination	Number of participants with clinically important treatment-emergent abnormalities in physical examination were reported.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Percentage of Participants Who Reached HBsAg Less Than (<) 10 (International Units Per Milliliter [IU/mL]) at the End of the Induction Phase (EOI)	Percentage of participants who reached HBsAg <10 IU/mL at the end induction phase were reported.	At IP Week 36 and EOI; anytime up to IP Week 52 for Cohort 1; up to IP Week 36 for Cohort 2
Time to Achieve First Occurrence of HBsAg <10 IU/mL	Time to achieve first occurrence of HBsAg <10 IU/mL were reported. Time to HBsAg <10 IU/mL was defined as the number of days between the date of first study treatment intake and the date of the first occurrence of HBsAg <10 IU/mL. Kaplan-Meier method was used for the estimation.	From Baseline (Day 1 of IP) up to Follow-up phase Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Percentage of Participants Who Met Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at the End of Consolidation Phase	Percentage of participants meeting the protocol-defined NA treatment completion criteria at end of consolidation were reported. NA treatment completion criteria at CP Week 12 was defined as HBsAg <10 IU/mL; HBeAg-negative; HBV DNA <20 IU/mL, (that is, LLOQ); alanine aminotransferase(ALT) <3*ULN.	At CP Week 12 (for Cohort 1 and 2)
FU Phase: Percentage of Participants With HBsAg Seroclearance 48 Weeks After Stopping All Study Interventions of the Consolidation Phase and Without Restarting NA Treatment During Follow up Phase	Percentage of participants with HBsAg seroclearance 48 weeks after stopping all study interventions at the consolidation phase and without restarting NA treatment during follow up phase were reported. HBsAg seroclearance was defined as (quantitative) HBsAg < LLOQ (HBsAg 0.05 IU/mL).	FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <LLOQ 48 Weeks After Stopping All Study Interventions of the Consolidation Phase and Without Restarting NA Treatment During Follow up Phase	Percentage of participants with HBV DNA <LLOQ (<20 IU/mL) 48 weeks after stopping all study interventions of the consolidation phase and without restarting NA treatment during follow up phase were reported.	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Number of Participants With Off-treatment Virologic HBV Flares During Follow up Phase	Number of participants with off-treatment virologic HBV flares were reported. Virologic flare was defined as confirmed HBV DNA >peak threshold (lowest peak to qualify as virologic flare was HBV DNA >200 IU/mL) in participants who were off-treatment and had HBV DNA <LLOQ (<20 IU/mL) at the last observed time point on all study treatments. The 3 thresholds of virologic flare was 20,000 IU/mL, 2,000 IU/mL and 200 IU/mL. Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. Off-treatment was defined as the time period after stopping all study treatments (including NA).	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Number of Participants With Off-treatment Biochemical HBV Flares During Follow-up Phase	Number of participants with off-treatment biochemical HBV flares were reported. Biochemical flare was defined as first date of 2 consecutive visits with confirmed ALT and/or AST >=3*ULN and >=3*nadir (lowest value observed up to start of flare). Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. Off-treatment was defined as the time period after stopping all study treatments (including NA).	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Number of Participants With On-treatment Biochemical Flares During Follow-up Phase	Number of participants with on-treatment biochemical HBV flares were reported. Biochemical flare was defined as first date of 2 consecutive visits with confirmed ALT and/or AST >=3*ULN and >=3*nadir (lowest value observed up to start of flare). Confirmed means that the criteria was fulfilled at 2 or more consecutive time points or at the last observed time point. On-treatment was defined as the time period during which the participant received any of the study drugs.	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Number of Participants With Off-treatment Clinical Flares During Follow-up Phase	Clinical flares occurred either when a virologic flare (confirmed HBV DNA >peak threshold) & biochemical flare (ALT and/or AST >=3*ULN & >=3*nadir [lowest value observed during off-treatment period up to time point of meeting the flare criteria]) overlapped in time or when a biochemical flare started within 4 weeks following the end of a virologic flare. The HBV DNA thresholds were: 20,000 IU/mL, 2,000 IU/mL and 200 IU/mL. Confirmed means that criteria was fulfilled at 2 or more consecutive time points or at last observed time point. Off-treatment was defined as time period after stopping all study drugs (including NA). The start date of a clinical flare was minimum start date of virologic flare and biochemical flare.	FU phase: FU Week 1 up to FU Week 48(up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Percentage of Participants Who Required NA Re-treatment During Follow-Up Phase	Percentage of participants who required NA re-treatment during follow-up phase were reported. A responder was defined as a participant who met the criteria for NA re-treatment at any time during follow-up, for those participants who met the NA treatment completion criteria at any time during the study and actually stopped NA treatment.	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
FU Phase: Percentage of Participants Who Achieved Reduction (Sustained) in HBsAg Response (Per Definition 1) at Follow-up Week 48	Percentage of participants with sustained (reduction) HBsAg response (per Definition 1) were reported. Sustained HBsAg response (definition 1) was defined as: For participants with FU Week 48 data: participants who had a >1 log10 decline from baseline in HBsAg and HBsAg <000 IU/mL at FU Week 48. For participants without FU Week 48 data: participants who had a HBsAg decline from baseline of >2 log10 at FU Week 24 or >1.5 log10 at FU Week 36 (most recent value used) and had HBsAg <1000 IU/mL at the last available timepoint.	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants Who Achieved Reduction (Sustained) in HBsAg Response (Per Definition 2) at Follow-up Week 48	Percentage of participants with sustained (reduction) HBsAg response (per Definition 2) were reported. Sustained HBsAg response (per Definition 2) was defined as: for participants with a >1 log decline in HBsAg from baseline at last follow-up visit: Among the most recent three visits, the difference between log10 HBsAg at 2 of 3 last visit and 1 of 3 last visit was <0.2, and the difference between log10 HBsAg at 3 of 3 last visit and 1 of 3 last visit was <0.2.	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants Who Achieved Reduction (Sustained) in HBsAg Response (Per Definition 3) at Follow-up Week 48	Percentage of participants with sustained (reduction) HBsAg response (per definition 3) were reported. Sustained HBsAg response (per Definition 3) was defined as: for participants with a >1 log decline in HBsAg from baseline at last follow-up visit: Among the most recent three visits, the difference between log10 HBsAg at 2 of 3 last visit and 1 of 3 last visit was <0.2, and the difference between log10 HBsAg at 3 of 3 last visit and 1 of 3 last visit was <0.2 and had an HBsAg <1000 IU/mL at the last available timepoint.	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants Who Achieved Reduction (Sustained) in HBsAg Response (Per Definition 4) at Follow-up Week 48	Percentage of participants with sustained (reduction) HBsAg response per Definition 4 were reported. Sustained HBsAg response (per Definition 4) was defined as stable level, decreasing level, and increasing level. Stable level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was within 0.2 log10. Decreasing level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was less than -0.2 log10. Increasing level: when HBsAg change from consolidation week 12 to last available follow-up timepoint was more than 0.2 log10.	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With HBsAg Seroclearance at Follow-up Week 48	Percentage of Participants with HBsAg Seroclearance were reported. HBsAg seroclearance was defined as (quantitative) HBsAg level <LLOQ (<0.05 IU/mL).	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With HBeAg Seroclearance at Follow-up Week 48	Percentage of participants with HBeAg seroclearance were reported. HBeAg seroclearance was defined as (quantitative) HBeAg levels <LLOQ (<0.11 IU/mL).	At FU Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With 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]).	IP Week 24; CP: Week 12, FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With HBeAg Seroconversion	Percentage of participants with HBeAg seroconversion were reported. Seroconversion of HBeAg was defined as having achieved HBeAg seroclearance (defined as [quantitative] HBeAg <LLOQ [<0.11 IU/mL]) together with appearance of anti-HBe antibodies (defined as a baseline anti-HBe antibodies [qualitative] with a "negative" result and a post-baseline assessment with "positive" result).	CP: Week 12; FU phase: FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Change From Baseline Over Time in HBsAg Levels	Change from baseline over time in HBsAg levels at specified timepoints were reported	Baseline (Day 1 of IP), IP: Week 36; CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Change From Baseline Over Time in HBeAg Levels	Change from baseline over time in HBsAg levels at specified timepoints were reported.	Baseline (Day 1 of IP), IP: Week 36; CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Change From Baseline Over Time in HBV DNA Levels	Change from baseline over time in HBV DNA Levels at Specified Timepoints were reported.	Baseline (Day 1 of IP), IP: Week 36; CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Time to Achieve First HBsAg Seroclearance	Time to achieve first HBsAg seroclearance (defined as quantitative HBsAg <LLOQ; HBsAg <0.05 IU/mL) were reported. Time to HBsAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance. Kaplan-Meier method was used for the estimation.	From Baseline (Day 1 of IP) to Follow-up Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Time to Achieve First HBeAg Seroclearance	Time to achieve first occurrence of HBeAg seroclearance (HBeAg <LLOQ [<0.11 IU/mL]) were reported. Time to first occurrence of the HBeAg seroclearance was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBeAg seroclearance.	From Baseline (Day 1 of IP) to Follow-up Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Time to Achieve First HBV DNA <LLOQ	Time to achieve first occurrence of HBV DNA < LLOQ (<20 IU/mL) were reported. Time to first occurrence of the HBV DNA < LLOQ was defined as the number of days between the date of first study intervention intake and the date of the first occurrence of the HBV DNA < LLOQ.	From Baseline (Day 1 of IP) to Follow-up Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Percentage of Participants With HBeAg Levels Below Different Cut-offs	Percentage of participants with HBeAg levels below different cut-offs were reported. The cut-offs for HBeAg levels were : <LLOQ (<0.11 IU/mL), < 1 IU/mL, < 10 IU/mL, <100 IU/mL	IP: Week 36, CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With HBsAg Levels Below Different Cut-offs	Percentage of participants with HBsAg levels below different cut-offs were reported. The cut-offs for HBsAg level were: <LLOQ (<0.05 IU/mL), <1 IU/mL, <10 IU/mL, <100 IU/mL, <1000 IU/mL.	IP: Week 36, CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With HBV DNA Levels Below Different Cut-offs	Percentage of participants with HBV DNA levels below cut-offs were reported. The cut-offs for HBV DNA were as follows: <LLOQ (<20 IU/mL) for target detected and not detected, < LLOQ for target not detected , and < LLOQ for target detected, <60 IU/mL, <100 IU/mL, <200 IU/mL, <1000 IU/mL, <2000 IU/mL, <20000 IU/mL.	IP: Week 36; CP: Week 12; FU phase: Week 48 (Week 112 [Cohort 1]; Week 96 [Cohort 2])
Percentage of Participants With Virologic Breakthrough	Percentage of participants with virologic breakthrough on treatment were reported. Virological breakthrough was defined as confirmed on-treatment HBV DNA increase by >1 log10 IU/mL from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level < LLOQ (<20 IU/mL) or confirmed on-treatment HBV DNA level >200 IU/mL in participants who had on-treatment HBV DNA level <LLOQ of the HBV DNA assay. Confirmed HBV DNA increase/level means that the criterion was fulfilled at 2 or more consecutive time points or at the last observed on-treatment time point.	IP: From Day 1 up to end of IP (up to Week 52 for Cohort 1; up to Week 36 for Cohort 2); CP: CP Week 1 up to CP Week 12 (for Cohort 1 and 2); FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Percentage of Participants Who Reached HBV DNA Undetectability After Re-start of NA Treatment During Follow-up	Percentage of participants who reached HBV DNA undetectability after re-start of NA treatment during follow-up were reported. Undetectability of HBV DNA was defined as HBV DNA<LLOQ that is <20 IU/mL.	FU phase: FU Week 1 up to FU Week 48 (up to Week 112 [Cohort 1]; up to Week 96 [Cohort 2])
Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (Molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924])	Cmax of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Noncompartmental analysis were conducted to analyze Cmax JNJ-73763989 and its molecules	IP : Predose (0 hour), post dose on 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 hours on IP Week 24; CP: Predose (0 hour), post dose on 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 hours on CP Week 8
Time to Reach the Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (Molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924])	Time to reach the maximum observed plasma concentration (tmax) of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted to analyze tmax of JNJ-73763989 and its molecules.	IP : Predose (0 hour), post dose on 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 hours on IP Week 24; CP: Predose (0 hour), post dose on 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 24 hours on CP Week 8
Plasma Concentration 24 Hours After Administration (C24h) of JNJ-73763989 (Molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924])	Plasma concentration 24 hours after administration (C24h) of JNJ-73763989 (molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted to analyze C24h of JNJ-73763989 and its molecules.	IP: 24 hours post dose on Week 24 visit; CP: 24 hours post dose on Week 8 visit
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours [AUC (0- 24 Hours)] of JNJ-73763989 (Molecules: JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924])	Area under the plasma concentration-time curve from time zero to 24hours (AUC0 to 24h) of JNJ-73763989 (molecules:JNJ-73763976 [JNJ3976], JNJ-73763924 [JNJ-3924]) were reported. Non-compartmental analysis were conducted toanalyze AUC0 to 24h of JNJ-73763989 and its molecules.	IP: 24 hours post dose on Week 24 visit; CP: 24 hours post dose on Week 8 visit

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): September 14, 2020
• Primary Completion (Actual): August 29, 2023
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 23, 2025
• Last Verified: June 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; Virus Diseases; 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; 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
• Other Study ID Numbers: CR108815; 73763989PAHPB2005 (Other Identifier: Janssen Research & Development, LLC); 2019-004978-26 (EudraCT Number)

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 and 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
• product manufactured in and exported from the U.S.: No