A Phase 1b, Open-label, Single-arm, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Treatment With JNJ-73763989, JNJ-64300535, and Nucleos(t)Ide Analogs in Virologically Suppressed, HBeAg-negative Participants With Chronic Hepatitis B Virus Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 13
- 主要终点
- Percentage of Participants with a Reduction of at Least 2 log10 International Units per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline to Week 36
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of the study intervention based on hepatitis B surface antigen (HBsAg) levels.
详细描述
JNJ-73763989 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. JNJ-64300535 is a DNA vaccine encoding the core protein and the Polymerase (Pol) protein of HBV. The therapeutic vaccine aims at inducing T-cell-specific immunity against HBV antigens in participants with chronic hepatitis B (CHB). Selected nucleos(t)ide analogs (NAs) used in this study are approved treatments of chronic HBV infection. This study is designed to assess efficacy, safety, and tolerability of a 24-week (Day 1 to Week 24) combination treatment with JNJ-73763989 + NA + JNJ-64300535. The study consists of a Screening phase (4 weeks), Treatment period with JNJ-73763989, NA and JNJ-64300535 (187 days), and a follow-up period (FU Week 1 till FO Week 48). Safety will be assessed by adverse events (AEs), clinical safety laboratory assessments, electrocardiograms (ECGs), vital signs and physical examinations. The total duration of the study is up to 88 weeks (including 4 weeks of screening).
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator
- •Participants must have a body mass index (BMI; weight in kilograms [kg] divided by the square of height in meters) between 19.0 and 32.0 kilograms per meter square (kg/m^2), extremes included
- •A woman of childbearing potential must have a negative highly sensitive serum pregnancy test (beta-human chorionic gonadotropin) at screening and a negative urine pregnancy test on Day 1 before the first dose of study intervention
- •Participants must have chronic hepatitis B virus (HBV) infection. HBV infection must be documented by serum hepatitis B surface antigen (HBsAg) positivity at screening. In addition, chronicity must be documented by any of the following, at least 6 months prior to screening: serum HBsAg positivity, hepatitis B e antigen (HBeAg) positivity or HBV deoxyribonucleic acid (DNA) positivity, alanine aminotransferase (ALT) elevation above upper limit of normal (ULN) without another cause than HBV infection, documented transmission event. If none of the above are available, the following ways of documenting chronicity are acceptable at the time of screening: liver biopsy with changes consistent with chronic HBV, or absence of marker for acute HBV infection such as positive immunoglobulin M (IgM) anti- hepatitis B surface protein (HBs) and anti- hepatitis B core protein (HBc) antibodies. Virologically suppressed participants should: a) be HBeAg-negative and anti- hepatitis B e (HBe) positive, b) be on stable HBV treatment, defined as currently receiving nucleos(t)ide analog (NA) treatment for at least 6 months prior to screening and having been on the same NA treatment regimen (at the same dose) as used in this study for at least 3 months at the time of screening, c) have serum HBV deoxyribonucleic acid (DNA) less than (<) 60 International units per milliliter (IU/mL) on 2 sequential measurements at least 6 months apart (one of which is at screening), and d) have documented ALT values <2.0* ULN on 2 sequential measurements at least 6 months apart (one of which is at screening)
- •Participants must have: a) Fibroscan liver stiffness measurement less than or equal to (<=) 9.0 kPa within 6 months prior to screening or at the time of screening, or b) If a Fibroscan result is not available: a liver biopsy result classified as Metavir F0-F2 within 1 year prior to screening
排除标准
- •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 a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which are considered cured with minimal risk of recurrence)
- •Participants with any history of or current clinically significant skin disease requiring regular or periodic treatment
- •Participants with clinically relevant alcohol or drug abuse within 12 months of screening
- •Participants who had major surgery (example, requiring general anesthesia), excluding diagnostic surgery, within 12 weeks before screening; or will not have fully recovered from surgery; or have surgery planned during the time of expected participation in the study
研究组 & 干预措施
JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate [ETV], Tenofovir disoproxil or Tenofovir alafemide [TAF]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.
干预措施: JNJ-73763989 (Drug)
JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate [ETV], Tenofovir disoproxil or Tenofovir alafemide [TAF]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.
干预措施: JNJ-64300535 (Biological)
JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate [ETV], Tenofovir disoproxil or Tenofovir alafemide [TAF]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.
干预措施: ETV monohydrate (Drug)
JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate [ETV], Tenofovir disoproxil or Tenofovir alafemide [TAF]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.
干预措施: Tenofovir disoproxil (Drug)
JNJ-73763989 plus JNJ-64300535 plus Nucleos(t)ide Analogs (NAs)
Participants will receive JNJ-73763989 subcutaneous (SC) injection once every 4 weeks (q4w), NA (either Entecavir monohydrate [ETV], Tenofovir disoproxil or Tenofovir alafemide [TAF]) oral tablets once daily (qd) and JNJ-64300535 intramuscular (IM) injection q4w. From day 187, participants will receive treatment with NA oral tablets qd up to Week 36.
干预措施: TAF (Drug)
结局指标
主要结局
Percentage of Participants with a Reduction of at Least 2 log10 International Units per Milliliter (IU/mL) in Hepatitis B Surface Antigen (HBsAg) Levels from Baseline to Week 36
时间窗: Baseline to Week 36 (end of study intervention)
Percentage of participants with a reduction of at least 2 log10 IU/mL in HBsAg levels from baseline to Week 36 will be reported.
次要结局
- Percentage of Participants Meeting Nucleos(t)ide Analog (NA) Treatment Completion Criteria(Week 38 and Week 40)
- Percentage of Participants with Virological Breakthrough(Up to Week 36)
- Time to Achieve HBsAg Seroclearance(Up to Week 84)
- Percentage of Participants with Viral Flares(From Week 36 to Week 84)
- Percentage of Participants with at Least 3-fold Increase in Hepatitis B Virus (HBV)- Specific T-Cell Response Against Vaccine Antigen HBV Core and/or Pol(From Day 103 up to Week 84)
- Change from Start of Vaccination Over Time in HBsAg Levels(From Day 103 up to Week 84)
- Percentage of Participants with HBsAg, HBV Deoxyribonucleic Acid (DNA) and Alanine Aminotransferase (ALT) Levels Below/Above Different Cut-offs(Up to Week 84)
- Percentage of Participants with HBsAg Seroclearance at Week 60 and Week 84(Weeks 60 and 84)
- Percentage of Participants with Biochemical Flares(From Week 36 to Week 84)
- Percentage of Responders Against Vaccine Antigen HBV Core and/or Pol(Week 28)
- Percentage of Participants with Serious AEs(Up to Week 84)
- Percentage of Participants with Abnormalities in Vital Signs(Up to Week 84)
- Percentage of Participants with Abnormalities in Physical Examinations(Up to Week 84)
- Number of TriGrid Delivery System (TDS)-Intramuscular (IM) version 2.0 Device Fault Conditions by Type(From Day 103 to Day 187)
- Percentage of Participants with Adverse Events (AEs)(Up to Week 84)
- Percentage of Participants with Abnormalities in 12- lead Electrocardiograms (ECGs)(Up to Week 84)
- Percentage of Participants with HBsAg Seroclearance(Up to Week 84)
- Percentage of Participants with HBsAg Seroconversion(Up to Week 84)
- Time to Achieve HBsAg Seroconversion(Up to Week 84)
- Percentage of Participants with HBV DNA <LLOQ at Week 60 and Week 84(Weeks 60 and 84)
- Percentage of Participants with Abnormalities in Clinical Laboratory Tests(Up to Week 84)
- Percentage of Participants with Solicited Local AEs for JNJ-64300535 up to 7 Days Post Each Vaccination(7 days post each vaccination (Up to Day 194))
- Percentage of Participants with Solicited Systematic AEs for JNJ-64300535 up to 7 Days Post Each Vaccination(7 days post each vaccination (Up to Day 194))
- Change from Baseline Over Time in HBsAg Levels(Baseline up to Week 84)