A Phase 2, Multicenter, Randomized, Double-blind, Placebo-Controlled Study With Deferred Active Treatment to Investigate the Efficacy, Safety, and Pharmacokinetics of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 101
- 主要终点
- Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)
研究概览
简要总结
The purpose of the study is to evaluate on-treatment efficacy against hepatitis D virus (HDV) of JNJ-73763989 + nucleos(t)ide analog (NA) regimen compared to NA alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
- •Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
- •For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values >= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (<=) 10000 IU/mL at screening or HDV RNA values at screening are <= 100000 IU/mL
- •Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
- •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
- •Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of >= 140000 per deciliter (dL) for enrollment into Part-2
排除标准
- •Evidence of infection with hepatitis A, C, 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 or any laboratory abnormalities indicating a reduced liver function as defined in the protocol
- •Evidence of liver disease of non-HBV/HDV etiology
- •Signs of hepatocellular carcinoma (HCC)
- •Significant laboratory abnormalities as defined in the protocol at screening
- •Participants with a history of malignancy within 5 years before screening
- •Abnormal sinus rhythm or ECG parameters at screening as defined in the protocol
- •History of or current cardiac arrhythmia or history or clinical evidence of significant or unstable cardiac disease
- •Participants with any current or previous illness for which, in the opinion of the investigator and/or sponsor, participation would not be in the best interest of the participant
- •History of or current clinically significant skin disease or drug rash
- •Participants with known allergies, hypersensitivity, or intolerance to JNJ-3989 or its excipients or excipients of the placebo content
- •Contraindications to the use of entecavir (ETV), tenofovir disoproxil, or tenofovir alafenamide (TAF) per local prescribing information
- •Participants who have taken any therapies disallowed per protocol
- •Female participants who are pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
- •Male participants who plan to father a child while enrolled
- •Participants who had or planned major surgery, (example, requiring general anesthesia) or who have received an organ transplant
- •Vulnerable participants (example, incarcerated individuals, individuals under a legal protection measure)
研究组 & 干预措施
Immediate Active Treatment arm: JNJ-73763989 + NA
Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir [ETV], tenofovir disoproxil, or tenofovir alafenamide [TAF]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.
干预措施: JNJ-73763989 (Drug)
Immediate Active Treatment arm: JNJ-73763989 + NA
Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir [ETV], tenofovir disoproxil, or tenofovir alafenamide [TAF]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.
干预措施: Entecavir (ETV) monohydrate (Drug)
Immediate Active Treatment arm: JNJ-73763989 + NA
Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir [ETV], tenofovir disoproxil, or tenofovir alafenamide [TAF]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.
干预措施: Tenofovir disoproxil (Drug)
Immediate Active Treatment arm: JNJ-73763989 + NA
Participants will receive JNJ-73763989 subcutaneous (SC) injection every 4 weeks (Q4W) along with NA (entecavir [ETV], tenofovir disoproxil, or tenofovir alafenamide [TAF]) once daily for 144 Weeks in Part 1 and for at least 96 weeks in Part 2.
干预措施: Tenofovir alafenamide (TAF) (Drug)
Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
干预措施: JNJ-73763989 (Drug)
Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
干预措施: Entecavir (ETV) monohydrate (Drug)
Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
干预措施: Tenofovir disoproxil (Drug)
Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
干预措施: Tenofovir alafenamide (TAF) (Drug)
Deferred Active Treatment arm: Placebo+NA+JNJ-73763989+NA
Participants will receive matching placebo to JNJ-73763989 SC injection Q4W along with NA (ETV, tenofovir disoproxil, or TAF) once daily for 52 Weeks followed by JNJ-73763989 SC injection Q4W along with NA once daily for 96 weeks in Part 1 and for at least 48 weeks in Part 2.
干预措施: Placebo (Drug)
结局指标
主要结局
Double-blind: Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)
时间窗: At Week 48
Percentage of participants with HDV RNA greater than or equal to (\>=) 2 log10 International Units Per Milliliter (IU/mL) decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. Target not detected (TND) was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT less than (\<) upper limit of normal (ULN) with ULN = 34 units per liter (U/L) for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With ALT at Week 48 (Multiple Imputation Approach)
时间窗: At Week 48
Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
Double-blind: Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT at Week 48 (Multiple Imputation Approach)
时间窗: Week 48
Percentage of participants with HDV RNA \>=2 log10 IU/mL decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT \<ULN with ULN = 34 U/L for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
Double-blind:Part 1: Percentage of Participants With HDV Ribonucleic Acid (RNA) >=2 log10 IU/mL Decline From Baseline or HDV RNA Target Not Detected (TND) in Combination With Normal Alanine Aminotransferase (ALT) at Week 48 (Multiple Imputation Approach)
时间窗: Week 48
Percentage of participants with hepatitis D virus (HDV) RNA greater than or equal to (\>=) 2 log10 international units per milliliter (IU/mL) decline from baseline or HDV RNA TND in combination with normal ALT at Week 48 using multiple imputation approach was reported. TND was defined as no traces of HBV RNA were detected/found. Normal ALT was defined as ALT less than (\<) upper limit of normal (ULN) with ULN = 34 units per liter (U/L) for female and 43 U/L for male. The baseline assessment was defined as the last observed non-missing measurement before the date and time of the first administration of any of study intervention on Day 1. The multiple imputation approach was derived using a longitudinal multiple regression model to impute missing data.
次要结局
- Part 1: Change From Baseline in ALT(Baseline (Day 1), Week 48, FU Week 24)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Vital Signs(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144)
- Part 1: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Parts 1 and 2: Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA < Lower Limits of Quantification (LLOQ) at Week 48(Week 48)
- Parts 1 and 2: Percentage of Participants With Normal ALT at Week 48(Week 48)
- Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance at Week 48(Week 48)
- Parts 1 and 2: Percentage of Participants With >=2 Kilopascal (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE) (FibroScan) at Week 48(Week 48)
- Part 2: Percentage of Participants With Normal ALT(FU Week 24)
- Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND in Combination With Normal ALT(Week 48, FU Week 24)
- Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT(Week 48 and FU Week 24)
- Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline in Combination With Normal ALT(Week 48 and FU Week 24)
- Part 1: Percentage of Participants With HDV RNA TND in Combination With Normal ALT(Week 48 and FU Week 24)
- Part 2: Percentage of Participants With HDV RNA TND in Combination With Normal ALT(Week 48 and FU Week 24)
- Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND(Week 48 and FU Week 24)
- Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND(Week 48 and FU Week 24)
- Parts 1 and 2: Time to Reach HDV RNA >=2 log10 IU/mL Decline From Baseline or HDV RNA TND(Placebo + NA: From Day 1 up to Week 196; JNJ-3989 + NA: From Day 1 up to Week 192)
- Part 1: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline(Week 48 and FU Week 24)
- Part 2: Percentage of Participants With HDV RNA >=2 log10 IU/mL Decline From Baseline(Week 48 and FU Week 24)
- Part 1: Percentage of Participants With HDV RNA TND(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HDV RNA TND(Week 48, FU Week 24)
- Part 1: Percentage of Participants With Normal ALT(FU Week 24)
- Part 1: Change From Baseline in HDV RNA(Baseline (Day 1), Week 48)
- Part 2: Change From Baseline in HDV RNA(Baseline (Day 1), Week 48)
- Part 2: Change From Baseline in ALT(Baseline (Day 1), Week 48, FU Week 44)
- Parts 1 and 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Chemistry(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Hematology(Placebo + NA: DB Phase: Week 0 up to Week 52; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urinalysis(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Urine Chemistry(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in Clinical Laboratory Tests: Renal Biomarkers(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Worst Treatment-emergent Abnormalities in 12-Lead Electrocardiogram(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Clinically Significant Abnormalities in Physical Examination(Placebo + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 148, FUP Phase: Week 148 up to Week 196; JNJ-3989 + NA: DB Phase: Week 0 up to Week 52, OL Phase: Week 52 up to Week 144; FUP Phase: Week 144 up to Week 192)
- Parts 1 and 2: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroclearance(Week 48, FU Week 24)
- Part 1: Change From Baseline Over Time in HBsAg(Baseline (Day 1), Week 48, FU Week 24)
- Part 2: Change From Baseline Over Time in HBsAg(Baseline (Day 1), Week 48, FU Week 24)
- Part 1: Change From Baseline Over Time in Hepatitis B Virus e Antigen (HBeAg)(Baseline (Day 1), Week 48, FU Week 24)
- Part 2: Change From Baseline Over Time in HBeAg(Baseline (Day 1), Week 48, FU Week 24)
- Part 1: Change From Baseline Over Time in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA)(Baseline (Day 1), Weeks 48 , 136, EOS (FU Week 48))
- Part 2: Change From Baseline Over Time in HBV DNA(Baseline (Day 1), Weeks 48, 112, EOS (FU Week 48))
- Part 1: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HBsAg Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Part 1: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HBeAg Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HBV DNA Levels Below/Above Different Cut-offs(Week 48, FU Week 24)
- Part 1: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate(Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192)
- Part 2: Time to Reach HBsAg <1 IU/mL Based on Kaplan-Meier Estimate(Placebo + NA: From baseline up to Week 196; JNJ-3989 + NA: From baseline up to Week 192)
- Part 1: Percentage of Participants With HBV DNA Virologic Breakthrough(Week 48, FU Week 24)
- Part 2: Percentage of Participants With HBV DNA Virologic Breakthrough(Week 48, FU Week 24)
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3976(Weeks 4, 8, and 16)
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of JNJ-3924(Weeks 4, 8, and 16)
- Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3976(Predose up to 24 hours post dose on Weeks 4, 8, and 16)
- Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[0-24h]) of JNJ-3924(Predose up to 24 hours post dose on Weeks 4, 8, and 16)
- Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3976(Weeks 4, 8, and 16)
- Parts 1 and 2: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Time (AUC[0-last]) of JNJ-3924(Weeks 4, 8, and 16)
- Part 1: Percentage of Participants With >=2 Kilopascals (kPa) Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by Vibration-controlled Transient Elastography (VCTE; FibroScan)(Baseline, EOS (FU Week 48))
- Part 2: Percentage of Participants With >=2 kPa Reduction From Baseline in Liver Stiffness Measurement (LSM) Assessed by VCTE (FibroScan)(Baseline, EOS (FU Week 48))
- Part 1: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan)(Baseline, Week 48, FU Week 24)
- Part 2: Change From Baseline in LSM Over Time Assessed by VCTE (FibroScan)(Baseline, Week 48, FU Week 24)
- Part 1: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Part 2: Percentage of Participants With Sustained HDV Response Off-treatment Post End of JNJ-3989 Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Part 1: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Part 2: Percentage of Participants With HDV Relapse Post End of JNJ-3989 Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Parts 1 and 2: Percentage of Participants With Sustained HBV Response Off-treatment Post End of JNJ-3989 Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Part 1: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)
- Part 2: Percentage of Participants With HBV Flare (Virologic, Biochemical, and Clinical) Post End of Treatment(JNJ-73763989 (JNJ-3989) + Nucleos(t)Ide Analog (NA): Post end of treatment (Week 144) up to FU Week 48; Placebo + NA: Post end of treatment (Week 148) up to FU Week 48)