Hepatitis B, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) changes from baseline for the treatment regimens of 24 weeks of JNJ-73763989 + 24 weeks of nucleos(t)ide analog (NA) + 12 or 24 weeks of pegylated interferon alpha-2a (PegIFN-alpha-2a) (with immediate or delayed start of PegIFN-alpha-2a treatment).
Detailed description
JNJ-73763989 (JNJ-3989) is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism. Combination treatment with JNJ-73763989 and NA has the potential to specifically decrease HBV viral antigen levels and inhibit viral replication. Since HBsAg is immune suppressive, the direct reduction of HBsAg levels by JNJ-73763989 is anticipated to contribute to the restoration of the immune response that is impaired in chronic HBV infection. Pegylated interferon (PegIFN) is an approved drug for the treatment of chronic HBV infection and after a finite treatment duration of 48 weeks results in slightly increased HBsAg seroclearance rates. The primary hypothesis of this study is that at least one of the combination regimens of JNJ-73763989+NA+PegIFN-alpha-2a is more efficacious than NA treatment alone (standard of care), as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4 weeks), Treatment Period (24 weeks) and Follow-up (FU) Period (48 weeks), starting at Week 24. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 76 weeks (including screening period).
Interventions
DRUGJNJ-73763989
JNJ-73763989 will be administered subcutaneously once every 4 weeks.
DRUGPegIFN-alpha-2a
PegIFN-alpha-2a will be administered subcutaneously once weekly.
DRUGTenofovir disoproxil
Tenofovir disoproxil film-coated tablet will be administered orally once daily.
DRUGTAF
TAF film-coated tablet will be administered orally once daily.
DRUGETV
ETV film-coated tablet will be administered orally once daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening * Participants must have a body mass index between 18.0 and 35.0 kilograms per meter square (kg/m\^2) inclusive * Participants with chronic hepatitis B who should: a) be chronic hepatitis B e antigen (HBeAg) -negative; b) be anti-HBe antibody-positive; c) be currently receiving nucleos(t)ide analog (NA) treatment for at least 2 years prior to screening; d) have serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than (\<) 60 international unit/milliliter (IU/mL) on 2 sequential measurements at least 6 months apart; e) have alanine aminotransferase (ALT) values \< 2.0x upper limit of normal (ULN) on 2 sequential measurements at least 6 months apart * Hepatitis B surface antigen (HBsAg) greater than (\>) 5 IU/mL at screening * Fibroscan liver stiffness measurement less than or equal to (\<=) 9.0 kilopascal (kPa) within 6 months prior to screening
Exclusion criteria
* History or signs of cirrhosis or portal hypertension * Evidence of hepatitis A, C, D, E virus infection, or human immunodeficiency virus (HIV) infection * Liver disease of non-HBV etiology * Clinically relevant alcohol or drug abuse within 12 months of screening * Participants who meet any of the additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Reduction of at Least 2log10 International Units Per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline at Week 24 (End of Study Intervention [EOSI]) | Week 24 | Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serious Adverse Events (SAEs) | Up to 1 month 26 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. |
| Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Up to 1 month 26 days | Percentage of participants with abnormalities in clinical laboratory tests including hematology, blood coagulation, blood biochemistry, urinalysis, urine chemistry, renal biomarkers, were reported. |
| Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs) | Up to 1 month 26 days | Percentage of participants with abnormalities in 12-Lead ECGs were reported. |
| Percentage of Participants With Abnormalities in Vital Signs | Up to 1 month 26 days | Percentage of participants with abnormalities in vital signs were reported. |
| Percentage of Participants With Abnormalities in Ophthalmologic Examination | Weeks 8 and 20 | Percentage of participants with abnormalities in ophthalmologic examination were planned to be reported. |
| Percentage of Participants With Abnormalities in Physical Examination | Week 24 | Percentage of participants with abnormalities in physical examination were planned to be reported. |
| Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria Based on the Week 24 (EOSI) or Follow-up Week 2 Visits | Week 24 (EOSI) and follow-up Week 2 | Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or follow-up Week 2 visits was planned to be reported. NA treatment completion criteria were as follows: (a) participant had alanine transaminase (ALT) \<3\*upper limits of normal (ULN); (b) participant had Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) \<20 international units per milliliter (IU/mL); (c) participant was Hepatitis B e antigen (HBeAg)-negative; (d) participant had Hepatitis B surface antigen (HBsAg\<10 IU/mL. |
| Percentage of Participants With HBsAg Seroclearance at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment | Follow-up Weeks 24 and 48 | Percentage of participants with HBsAg seroclearance at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<lower limit of quantitation (LLOQ). LLOQ is 0.05 International Units per milliliter (IU/mL). |
| Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < (Less Than) LLOQ at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment | Follow-up Weeks 24 and 48 | Percentage of participants with HBV DNA \<LLOQ at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. LLOQ is 0.05 IU/mL. |
| Percentage of Participants With Virologic Flares | Up to 1 month 26 days | Percentage of participants with virologic flares were reported. The start of a confirmed virologic flare is defined as the first date of two consecutive visits with HBV DNA \>200 IU/mL. The end date of the same confirmed virologic flare is defined as the first date when HBV DNA value returns to less than or equal to (\<=)200 IU/mL or the date of NA treatment restart, whichever comes first. |
| Percentage of Participants With Biochemical Flares | Up to 1 month 26 days | Percentage of participants with biochemical flares were reported. The start date of a confirmed off-treatment biochemical flare: the first date of two consecutive visits with ALT and/or AST\>=3x ULN and \>=3x off-treatment/on-treatment nadir (that is, lowest value observed during off-treatment period up to the time point of meeting the biochemical flare criteria) while the participant does not receive any of the study interventions. The end date of the same off-treatment/on-treatment biochemical flare: the first date when there is a 50% reduction from the peak ALT and/or AST level & \<3x ULN. |
| Percentage of Participants With Adverse Events (AEs) | Up to 1 month 26 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Percentage of Participants With HBsAg, Hepatitis B e Antigen (HBeAg), HBV DNA, and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs | Up to 72 weeks | Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs were planned to be reported. |
| Percentage of Participants With HBsAg Seroconversion | Up to 72 weeks | Percentage of participants with HBsAg seroconversion were planned to be reported. Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL. |
| Change From Baseline in HBsAg Over Time | Baseline up to Week 72 | Change from baseline in HBsAg over time were planned to be reported. |
| Time to Achieve HBsAg Seroclearance | Up to 72 weeks | Time to achieve HBsAg seroclearance were planned to be reported. Time to achieve HBsAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance (that is, the date of the first HBsAg seroclearance - the date of first study intervention intake + 1). Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<LLOQ. LLOQ is 0.05 IU/mL. |
| Time to Achieve HBsAg Seroconversion | Up to 72 weeks | Time to achieve HBsAg seroconversion were planned to be reported. Time to achieve HBsAg seroconversion is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance and appearance of anti-HBs antibodies (that is, the date of the first HBsAg seroclearance and anti-HBs antibodies - the date of first study intervention intake + 1). Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL. |
| Time to Achieve HBV DNA <Lower Limit of Quantitation (LLOQ) | Up to 72 weeks | Time to achieve HBV DNA \<LLOQ were planned to be reported. Time to achieve HBV DNA \<LLOQ is defined as the number of days between HBV DNA \>LLOQ for participants who re-treated with NA and the date of the first occurrence of HBV DNA \< LLOQ after NA re-treatment (that is, the date of the HBV DNA \< LLOQ after being re-treated with NA - the date of first occurrence of HBV DNA\>LLOQ + 1). LLOQ is 0.05 IU/mL. |
| Percentage of Participants With Virologic Breakthrough | Up to Week 24 | Percentage of participants with virologic breakthrough were planned to be reported. HBV virological breakthrough is defined as having a confirmed on-treatment HBV DNA increase by \>1 log10 from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level below the LLOQ or a confirmed on-treatment HBV DNA level \>200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ. LLOQ is 0.05 IU/mL. |
| Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) | Up to 72 weeks | Serum concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) were planned to be reported. |
| Serum Concentration of Nucleos(t)Ide Analog (NA) (Entecavir [ETV]) | Up to 72 weeks | Serum concentration of NA (ETV) was planned to be reported. |
| Serum Concentration of PegIFN-alpha-2a | Up to 72 weeks | Serum concentration of PegIFN-alpha-2a was planned to be reported. |
| Percentage of Participants Requiring Nucleos(t)Ide Analog (NA) Re-treatment | Up to 72 weeks | Percentage of participants requiring NA re-treatment were planned to be reported. |
Countries
Canada, Japan, Poland, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Only 1 participant was enrolled in the study in Arm 1: JNJ-73763989 + nucleos(t)ide analog (NA) + pegylated interferon alpha-2a (PegIFN-alpha-2a) but did not complete the study. Participants were also planned to be enrolled in Arms 2 and 3 but were not enrolled as the study terminated prematurely based on a strategic decision and not for safety reasons.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a Participants received JNJ-73763989 200 milligrams (mg) subcutaneous (SC) injection on Day 1 plus NA treatment (entecavir \[ETV\] 0.5 mg tablet) orally once daily from Day 1 to Day 16 plus pegylated interferon alpha-2a (PegIFN-alpha-2a) 180 micrograms (mcg) SC injection on Days 1, 8, and 15. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Premature termination of study | 1 |
Baseline characteristics
| Characteristic | Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 46 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Percentage of Participants With a Reduction of at Least 2log10 International Units Per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline at Week 24 (End of Study Intervention [EOSI])
Percentage of participants with a reduction of at least 2log10 IU/mL in HBsAg levels from baseline at Week 24 (EOSI) were planned to be reported.
Time frame: Week 24
Population: Full analysis set (FAS) included all participants who were randomly assigned to an intervention arm in the intervention-specific appendix (ISA) and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Change From Baseline in HBsAg Over Time
Change from baseline in HBsAg over time were planned to be reported.
Time frame: Baseline up to Week 72
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria Based on the Week 24 (EOSI) or Follow-up Week 2 Visits
Percentage of participants meeting the protocol-defined NA treatment completion criteria based on the Week 24 (EOSI) or follow-up Week 2 visits was planned to be reported. NA treatment completion criteria were as follows: (a) participant had alanine transaminase (ALT) \<3\*upper limits of normal (ULN); (b) participant had Hepatitis B Virus (HBV) Deoxyribonucleic acid (DNA) \<20 international units per milliliter (IU/mL); (c) participant was Hepatitis B e antigen (HBeAg)-negative; (d) participant had Hepatitis B surface antigen (HBsAg\<10 IU/mL.
Time frame: Week 24 (EOSI) and follow-up Week 2
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants Requiring Nucleos(t)Ide Analog (NA) Re-treatment
Percentage of participants requiring NA re-treatment were planned to be reported.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs)
Percentage of participants with abnormalities in 12-Lead ECGs were reported.
Time frame: Up to 1 month 26 days
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in 12-Lead Electrocardiograms (ECGs) | 0 Percentage of participants |
Secondary
Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Percentage of participants with abnormalities in clinical laboratory tests including hematology, blood coagulation, blood biochemistry, urinalysis, urine chemistry, renal biomarkers, were reported.
Time frame: Up to 1 month 26 days
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Hematology | 0 Percentage of participants |
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Blood coagulation | 0 Percentage of participants |
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Blood biochemistry | 0 Percentage of participants |
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Urinalysis | 0 Percentage of participants |
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Urine chemistry | 0 Percentage of participants |
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Clinical Laboratory Tests | Renal biomarker | 0 Percentage of participants |
Secondary
Percentage of Participants With Abnormalities in Ophthalmologic Examination
Percentage of participants with abnormalities in ophthalmologic examination were planned to be reported.
Time frame: Weeks 8 and 20
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Abnormalities in Physical Examination
Percentage of participants with abnormalities in physical examination were planned to be reported.
Time frame: Week 24
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Abnormalities in Vital Signs
Percentage of participants with abnormalities in vital signs were reported.
Time frame: Up to 1 month 26 days
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Abnormalities in Vital Signs | 0 Percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Up to 1 month 26 days
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Adverse Events (AEs) | 0 Percentage of participants |
Secondary
Percentage of Participants With Biochemical Flares
Percentage of participants with biochemical flares were reported. The start date of a confirmed off-treatment biochemical flare: the first date of two consecutive visits with ALT and/or AST\>=3x ULN and \>=3x off-treatment/on-treatment nadir (that is, lowest value observed during off-treatment period up to the time point of meeting the biochemical flare criteria) while the participant does not receive any of the study interventions. The end date of the same off-treatment/on-treatment biochemical flare: the first date when there is a 50% reduction from the peak ALT and/or AST level & \<3x ULN.
Time frame: Up to 1 month 26 days
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Biochemical Flares | 0 Percentage of participants |
Secondary
Percentage of Participants With HBsAg, Hepatitis B e Antigen (HBeAg), HBV DNA, and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs
Percentage of participants with HBsAg, HBeAg, HBV DNA, and ALT levels below/above different cut-offs were planned to be reported.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With HBsAg Seroclearance at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment
Percentage of participants with HBsAg seroclearance at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<lower limit of quantitation (LLOQ). LLOQ is 0.05 International Units per milliliter (IU/mL).
Time frame: Follow-up Weeks 24 and 48
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With HBsAg Seroconversion
Percentage of participants with HBsAg seroconversion were planned to be reported. Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < (Less Than) LLOQ at Follow-up Weeks 24 and 48 Without Re-starting NA Treatment
Percentage of participants with HBV DNA \<LLOQ at follow-up Weeks 24 and 48 without re-starting NA treatment were planned to be reported. LLOQ is 0.05 IU/mL.
Time frame: Follow-up Weeks 24 and 48
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Up to 1 month 26 days
Population: Safety analysis set included all participants who received at least 1 dose of study intervention within the ISA.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Serious Adverse Events (SAEs) | 0 Percentage of participants |
Secondary
Percentage of Participants With Virologic Breakthrough
Percentage of participants with virologic breakthrough were planned to be reported. HBV virological breakthrough is defined as having a confirmed on-treatment HBV DNA increase by \>1 log10 from nadir level (lowest level reached during treatment) in participants who did not have on-treatment HBV DNA level below the LLOQ or a confirmed on-treatment HBV DNA level \>200 IU/mL in participants who had on-treatment HBV DNA level below the LLOQ. LLOQ is 0.05 IU/mL.
Time frame: Up to Week 24
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Percentage of Participants With Virologic Flares
Percentage of participants with virologic flares were reported. The start of a confirmed virologic flare is defined as the first date of two consecutive visits with HBV DNA \>200 IU/mL. The end date of the same confirmed virologic flare is defined as the first date when HBV DNA value returns to less than or equal to (\<=)200 IU/mL or the date of NA treatment restart, whichever comes first.
Time frame: Up to 1 month 26 days
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: JNJ-73763989+Nucleos(t)Ide Analog (NA)+PegIFN-alpha-2a | Percentage of Participants With Virologic Flares | 0 Percentage of participants |
Secondary
Serum Concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976)
Serum concentration of JNJ-73763989 (JNJ-73763924 and JNJ-73763976) were planned to be reported.
Time frame: Up to 72 weeks
Population: Pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Serum Concentration of Nucleos(t)Ide Analog (NA) (Entecavir [ETV])
Serum concentration of NA (ETV) was planned to be reported.
Time frame: Up to 72 weeks
Population: PK analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Serum Concentration of PegIFN-alpha-2a
Serum concentration of PegIFN-alpha-2a was planned to be reported.
Time frame: Up to 72 weeks
Population: PK analysis set included all participants who received at least 1 dose of study intervention and have at least 1 valid blood sample drawn for PK analysis. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Time to Achieve HBsAg Seroclearance
Time to achieve HBsAg seroclearance were planned to be reported. Time to achieve HBsAg seroclearance is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance (that is, the date of the first HBsAg seroclearance - the date of first study intervention intake + 1). Seroclearance of HBsAg is defined as a (quantitative) HBsAg level \<LLOQ. LLOQ is 0.05 IU/mL.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Time to Achieve HBsAg Seroconversion
Time to achieve HBsAg seroconversion were planned to be reported. Time to achieve HBsAg seroconversion is defined as the number of days between the date of first study intervention intake and the date of the first occurrence of HBsAg seroclearance and appearance of anti-HBs antibodies (that is, the date of the first HBsAg seroclearance and anti-HBs antibodies - the date of first study intervention intake + 1). Seroconversion of HBsAg is defined as having achieved HBsAg seroclearance (quantitative HBsAg level \<LLOQ) and appearance of anti-HBs antibodies. LLOQ is 0.05 IU/mL.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.
Secondary
Time to Achieve HBV DNA <Lower Limit of Quantitation (LLOQ)
Time to achieve HBV DNA \<LLOQ were planned to be reported. Time to achieve HBV DNA \<LLOQ is defined as the number of days between HBV DNA \>LLOQ for participants who re-treated with NA and the date of the first occurrence of HBV DNA \< LLOQ after NA re-treatment (that is, the date of the HBV DNA \< LLOQ after being re-treated with NA - the date of first occurrence of HBV DNA\>LLOQ + 1). LLOQ is 0.05 IU/mL.
Time frame: Up to 72 weeks
Population: FAS included all participants who were randomly assigned to an intervention arm in the ISA and received at least 1 dose of study intervention. The data was not collected and analyzed for this outcome measure due to premature termination of the study.