A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 26
- 主要终点
- Percentage of Participants Who Achieved Hepatitis B Surface Antigen (HBsAg) Seroclearance at Follow-up (FU) Week 24
研究概览
简要总结
The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.
详细描述
JNJ-73763989 (JNJ-3989) is a small interfering ribonucleic acid (siRNA) targeting all hepatitis B virus (HBV) messenger ribonucleic acid (mRNAs). The programmed cell death protein receptor-1 (PD-1) inhibitor aims at preventing the interaction of PD-1 with its ligands. The purpose of this study to determine whether at least one of the combination regimens of JNJ-3989 + PD-1 inhibitor + Nucleos(t)ide analog (NA) is more efficacious than JNJ-3989 + NA treatment. This study will be conducted in 3 periods: screening period, treatment period and follow-up (FU) period. Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Total duration of individual participation will be up to 78 weeks (including screening period).
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have chronic hepatitis B virus (HBV) infection
- •Participants must have fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kilopascal (kPa) or a liver biopsy result classified as metavir F0-F2
排除标准
- •Participants with evidence of hepatitis A virus infection (hepatitis A antibody immunoglobulin IgM), hepatitis C virus (HCV) infection (HCV antibody), hepatitis D virus (HDV) infection (HDV antibody), hepatitis E virus (HEV) infection (hepatitis E antibody IgM), or human immunodeficiency virus type 1 (HIV-1) or human immunodeficiency virus type 2 (HIV-2) infection (laboratory confirmed) 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
- •Participants with history or signs of cirrhosis or portal hypertension or signs of hepatocellular carcinoma (HCC) or clinically relevant renal abnormalities
- •Participants with personal/familial history/indicative of immune-mediated disease risk
研究组 & 干预措施
Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)
Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).
干预措施: JNJ-73763989 (Drug)
Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)
Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).
干预措施: PD-1 inhibitor (Drug)
Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)
Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).
干预措施: Tenofovir Disoproxil (Drug)
Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)
Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).
干预措施: Tenofovir Alafenamide (Drug)
Arm 1: JNJ-73763989 + PD-1 Inhibitor + Nucleos(t)ide analog (NA)
Participants will receive JNJ-73763989 subcutaneous (SC) injections and single dose of programmed cell death protein receptor-1 (PD-1) inhibitor as intravenous (IV) infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, tenofovir alafenamide [TAF] or entecavir [ETV]).
干预措施: Entecavir (Drug)
Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA
Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
干预措施: JNJ-73763989 (Drug)
Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA
Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
干预措施: PD-1 inhibitor (Drug)
Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA
Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
干预措施: Tenofovir Disoproxil (Drug)
Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA
Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
干预措施: Tenofovir Alafenamide (Drug)
Arm 2: JNJ-73763989 + PD-1 Inhibitor + NA
Participants will receive JNJ-73763989 SC injections and multiple doses of PD-1 inhibitor as IV infusion. Participants will also receive background treatment with NA (either tenofovir disoproxil, TAF or ETV).
干预措施: Entecavir (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Hepatitis B Surface Antigen (HBsAg) Seroclearance at Follow-up (FU) Week 24
时间窗: At FU Week 24
Percentage of participants who achieved HBsAg seroclearance at FU Week 24 were reported. Seroclearance of HBsAg was defined as a (quantitative) HBsAg level less than (\<) lower limit of quantification (LLOQ) (0.05 international unit per milliliters \[IU/mL\]).
次要结局
- Number of Participants With Abnormalities in Vital Signs(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) of Special Interest(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With Abnormalities in Physical Examinations(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With Abnormalities in Clinical Laboratory Parameters: Urinalysis(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Percentage of Participants With HBsAg Seroconversion(IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With TEAEs by Severity(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With Immune Related TEAEs(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With Abnormalities in 12-lead Electrocardiogram (ECGs)(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Percentage of Participants With Abnormalities in Clinical Laboratory Parameters: Hematology(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Number of Participants With Abnormalities in Clinical Laboratory Parameters: Clinical Chemistry(IP: Week 0 up to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Time to Achieve HBsAg Seroconversion(Week 0 up to FU Week 48 (up to Week 72))
- Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels(IP: Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, and End of Study Intervention (EOSI; Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48))
- Percentage of Participants With Change in HBsAg Levels Below/Above Different Cut-offs Over Time(IP: Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48))
- Percentage of Participants With HBsAg Seroclearance(IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48)
- Time to Achieve HBsAg Seroclearance(Week 0 up to FU Week 48 (up to Week 72))
- Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels Over Time(IP: Baseline, Weeks 2, 4, 8, 12, 16, 20 and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48))
- Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Level Below/Above Different Cut-offs Over Time(IP: Baseline, Weeks 2, 4, 8, 12, 16, 20, and EOSI (Week 24); FU Phase: FU Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48))
- Percentage of Participants With Hepatitis B e Antigen (HBeAg) Level Below/Above Different Cut-offs Over Time(IP: Baseline, Weeks 2, 4, 8, 12, 20, and EOSI (Week 24); FU Phase: FU Weeks 12, 16, 20, 24, 32, 40, 48, and EOS (last visit at FU Week 48))
- Percentage of Participants With Virologic Breakthrough(IP: Week 0 to Week 24; FU Phase: FU Week 1 up to FU Week 48)