A Phase 2, Open-label, Single-arm, Multicenter Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of Treatment With JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 11
- 主要终点
- Percentage of Participants With a Reduction of at Least 2 log10 International Unit/Millilitres (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline to Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) levels of the study intervention (that is, JNJ-73763989 + JNJ-56136379 + nucleos[t]ide analog [NA] and pegylated interferon alpha-2a [PegIFN-alpha2a]).
详细描述
This study is an intervention specific appendix to the Hepatitis B wings platform trial (PLATFORMPAHPB2001). The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but has been removed as part of amendment 3 of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Chronic hepatitis B virus (HBV) infection, hepatitis B e Antigen (HBeAg) positive or negative with suppressed viral replication under nucleos(t)ide analogue treatment for at least 6 months prior to screening
- •Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
- •Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
- •Must have serum HBsAg greater than (>) 100 international units per milliliter (IU/mL) at screening, as assessed by quantitative HBsAg assay
- •Must have a fibroscan stiffness measurement less than or equal to (<=) 9.0 Kilopascal (kPa) at screening
排除标准
- •Evidence of hepatitis A, C, D or E virus infection or human immunodeficiency, virus type 1 (HIV) 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
- •Contraindications to the use of pegylated interferon alpha-2a
研究组 & 干预措施
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2.
干预措施: JNJ-73763989 (Drug)
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2.
干预措施: Tenofovir disoproxil (Drug)
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2.
干预措施: Tenofovir alafenamide (TAF) (Drug)
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2.
干预措施: Entecavir (ETV) monohydrate (Drug)
Treatment Period (TP) 1 (JNJ-73763989 + Nucleos(t)ide Analog)+ TP 2 (TP 1+PegIFN-alpha2a)
Participants will receive combination treatment with JNJ-73763989+ nucleos(t)ide analog (NA) for 12 weeks during Treatment Period 1 and the participants who meet the eligibility criteria for PegIFN-alpha2a at Week 12 will receive combination treatment with JNJ-73763989 + NA plus PegIFN-α2a for 12 weeks during Treatment Period 2.
干预措施: PegIFN-alpha2a (Drug)
结局指标
主要结局
Percentage of Participants With a Reduction of at Least 2 log10 International Unit/Millilitres (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels From Baseline to Week 24
时间窗: From Baseline (Day 1) to Week 24
Percentage of participants with a reduction of at least 2 log10IU/mL in HBsAg levels from baseline to Week 24 were reported. A responder was defined as a participant with reduction of at least 2 log10 IU/mL in HBsAg levels from baseline at Week 24.
次要结局
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs) as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to Week 28)
- Percentage of Participants With HBsAg Levels Below Different Cut-offs(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Number of Participants With Clinically Significant Abnormalities in Physical Examination as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24)
- Number of Participants With Clinically Significant Abnormalities in Vital Signs as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Number of Participants With Clinically Significant Abnormalities in Laboratory Findings as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With Hepatitis B e Antigen (HBeAg) Levels Below Different Cut-offs(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Number of Participants With Abnormalities in Ophthalmic Examination as a Measure of Safety and Tolerability(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24)
- Percentage of Participants Meeting the Protocol-defined Nucleos(t)Ide Analog (NA) Treatment Completion Criteria at End of Study Intervention (EOSI)(At Week 24 (EOSI))
- Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Below Different Cut-offs(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With ALT Levels Greater Than or Equal to (>=) 3*ULN(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With HBeAg Seroconversion(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With HBsAg Seroconversion(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Change From Baseline Over Time in HBsAg Levels(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Change From Baseline Over Time in HBeAg Levels(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Change From Baseline Over Time in HBV DNA Levels(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Baseline (Day 1) up to Week 24; Follow-Up: From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Time to First Occurrence of HBsAg Seroclearance(From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Time to First Occurrence of HBeAg Seroclearance(From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Time to First Occurrence of HBV DNA < LLOQ(From Baseline (Day 1) up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With Virologic Breakthrough(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With HBsAg Seroclearance at Week 48 Without Re-starting NA Treatment(At Week 48 (24 weeks after completion of all study interventions at Week 24))
- Percentage of Participants With HBV DNA < LLOQ at Week 48 Without Re-starting NA Treatment(At Week 48 (24 weeks after completion of all study interventions at Week 24))
- Percentage of Participants With Biochemical Flares(Treatment Period 1: From Baseline (Day 1) up to Week 12; Treatment Period 2: From Week 12 up to Week 24; Follow-Up: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Percentage of Participants With Virologic Flares(Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Number of Participants Requiring NA Re-treatment(Follow-Up Period: From Week 24 up to follow-up Week 48 (with window period of +/- 4 days, that is Week 72.4))
- Maximum Observed Plasma Concentration (Cmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)(Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12)
- Plasma Concentration 24 Hours After Administration (C24h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)(Treatment Period 1: Day 1 Week 1; Treatment Period 2: Day 1, Week 12)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)(Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12)
- Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hour (AUC[0-24]h) of JNJ-73763989 (JNJ-73763976 and JNJ-73763924)(Treatment Period 1: Day 1, Week 1; Treatment Period 2: Day 1, Week 12)