A First-In-Human, Double-Blind, Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Reactogenicity, and Immunogenicity of JNJ-64300535, a DNA Vaccine, Administered by Electroporation-Mediated Intramuscular Injection, in Participants With Chronic Hepatitis B Who Are on Stable Nucleos(T)Ide Therapy and Virologically Suppressed
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 14
- 主要终点
- Number of Participants with Adverse Events (AEs) by Severity and Relationship to Study Treatment and Dose Level
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and reactogenicity of escalating doses of JNJ-64300535 delivered via electroporation-mediated intramuscular injection in nucleos(t)ide analogs (NA)-treated chronic hepatitis B (CHB) participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Has chronic hepatitis B virus envelope antigen (HBeAg) negative hepatitis B virus (HBV) infection documented by a positive hepatitis B virus surface antigen (HBsAg) test and/or detectable HBV deoxyribonucleic acid (DNA) at least 6 months prior to the screening visit
- •Is on a stable treatment with one of the approved oral nucleos(t)ide analogs (NA) polymerase inhibitors tenofovir alafenamide, tenofovir disoproxil fumarate, or entecavir for greater than or equal to (>=)12 months prior to screening. A history of switching between the above treatments is acceptable as long as it was not triggered by virologic failure
- •Must demonstrate HBV DNA levels less than (<)60 international unit/milliliter (IU/mL) on 2 occasions separated by greater than (>)6 months (of which one can be the screening assessment).
- •Has HBsAg levels at screening between 100 IU/mL and 10,000 IU/mL
- •Has normal alanine aminotransferase (ALT) levels for at least 6 months prior to baseline with no documented measurement exceeding 1.25 times upper limit of normal [ULN]). Minimal requirement is documentation of two ALT results within the year prior to baseline of which one can be the screening assessment.
排除标准
- •Presence of advanced hepatic fibrosis or cirrhosis in 1 of the assessments below done less than or equal to (<=)6 month prior to baseline: a. Metavir score 3 or 4 in a liver biopsy OR b. Fibroscan result of >9 kilopascal (kPa) OR c. Acoustic Radiation Force Impulse (ARFI) result of >=1.55 meter/second (m/s)
- •Clinical signs or history of liver cirrhosis or hepatic decompensation:
- •Metavir score 4 in a historical biopsy OR
- •ascites, esophageal varices, or hepatic encephalopathy OR
- •documentation of one of the following laboratory abnormality within 12 months of screening:
- •i. direct (conjugated) bilirubin >1.2 times upper limit of normal (ULN) OR ii. prothrombin time (PT) >1.2 times ULN OR iii. serum albumin <3.5 gram per deciliter (g/dL)
- •Positive serology test at screening for any of the following:
- •anti-hepatitis B surface (ant-HBs) antibodies
- •anti-human immunodeficiency virus (HIV)-1 or anti-HIV-2 antibodies
- •anti-hepatitis A virus (HAV) immunoglobulin M (IgM) antibodies
- •anti-hepatitis C virus (ant-HCV) antibodies
- •anti-hepatitis D virus (anti-HDV) antibodies
- •Participants with any evidence of liver disease of non-HBV etiology. This includes but is not limited to hepatitis A, C, or D virus infections (as above), drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cirrhosis, primary sclerosing cholangitis, non-alcoholic steatohepatitis or any other non-HBV liver disease considered clinically significant by the investigator
- •Has a history of persistent or recurrent hyperbilirubinemia unless explained by known Gilbert's Disease
- •History of blood disorders (bleeding problems or a blood clot, thalassemia major or sickle cell anemia).
- •History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions.
研究组 & 干预措施
Placebo + Nucleos(t)ide Analogs (NA)
Participants will receive placebo intramuscular (IM) injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
干预措施: Placebo (Biological)
Placebo + Nucleos(t)ide Analogs (NA)
Participants will receive placebo intramuscular (IM) injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
干预措施: Nucleos(t)ide Analogs (NA) (Drug)
JNJ-64300535 + NA
Participants will receive JNJ-64300535 IM injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
干预措施: JNJ-64300535 (Biological)
JNJ-64300535 + NA
Participants will receive JNJ-64300535 IM injection on Day 1, Week 4, and Week 12, along with standard of care NA treatment.
干预措施: Nucleos(t)ide Analogs (NA) (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs) by Severity and Relationship to Study Treatment and Dose Level
时间窗: Up to Week 16
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as follows: Mild = Grade 1, Moderate = Grade 2, Severe = Grade 3, Potentially life-threatening = Grade 4.
Number of Participants With Injection Site Reactions After Vaccination on Week 4
时间窗: Up to 7 days post-vaccination on Week 4
Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post-vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
Number of Participants With Injection Site Reactions After Vaccination on Week 12
时间窗: Up to 7 days post-vaccination on Week 12
Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post- vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
Number of Participants With Clinically Significant Changes in Physical Examination (Palpation of Lymph Nodes, Height, Body Weight, and Skin Examination) Findings
时间窗: Up to Week 16
Number of participants with clinically significant changes in physical examination parameters will be reported. Full physical examination (including palpation of lymph nodes, height, body weight, and skin examination) and symptom-directed physical examination will be performed.
Number of Participants With Laboratory Abnormalities
时间窗: Up to Week 16
Number of participants with laboratory abnormalities related to hematology, serum chemistry, coagulation, liver function tests and urinalysis will be reported. Laboratory abnormalities will be graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as follows: Mild = Grade 1, Moderate = Grade 2, Severe = Grade 3, Potentially life-threatening = Grade 4.
Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: Up to Week 16
Number of participants with clinically significant changes in the vital signs including blood pressure, pulse/heart rate, and body temperature will be reported.
Number of Participants With Acute Injection Site Reactions on Day 1
时间窗: From 0 to 2 hours post-vaccination on Day 1
Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
Number of Participants With Acute Injection Site Reactions at Week 4
时间窗: From 0 to 2 hours post-vaccination at Week 4
Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
Number of Participants With Acute Injection Site Reactions at Week 12
时间窗: From 0 to 2 hours post-vaccination at Week 12
Participants will be assessed for the acute injection site reactions. Acute reactions means the reactions which occur within 0 to 2 hours post-vaccination. Acute reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
Number of Participants With Injection Site Reactions After Vaccination on Day 1
时间窗: Up to 7 days post-vaccination on Day 1
Participants will be assessed for the Reactogenicity. Reactogenicity means injection site reactions which occur after 7 days post- vaccination. Severity of reactions will be graded as follows: Grade 0 = Normal, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life Threatening.
次要结局
- Percentage of Participants With a Positive Hepatitis B Virus (HBV) Specific T Cells Response(Day 1, Week 2, 6, 14, 24, 48, and 60)
- Time to Detection of HBV Specific T-Cell Responses(Day 1 up to Week 60)
- Percentage of CD4+ and CD8+ T-Cell Responses(Day 1, Week 2, 6, 14, 24, 48, and 60)
- Hepatitis B Antigen-Specific Cellular Immune Response(Day 1, Week 2, 6, 14, 24, 48, and 60)
- Number of TriGrid Delivery System (TDS)-Intramuscular (IM) v2.0 Device Fault Conditions by Type(Day 1, Week 4 and 12)