Comparison of the Immunogenicity and Safety of Various Investigational and Licensed Formulations of Hepatitis B Surface Antigen (HBsAg) Vaccines.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 713
- 试验地点
- 15
- 主要终点
- Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells .
研究概览
简要总结
The aim of this Observer-blind study is to compare different Adjuvant Systems with the same, well-known antigen (HBsAg) already used in the GSK marketed vaccines against Hepatitis B (Engerix-BTM and FendrixTM), in order to better understand the immune response induced by each of the Adjuvant System.
This Protocol Posting has been updated following Protocol amendment 6, October 2009. The section impacted is Eligibility Criteria
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects must satisfy the following criteria at study entry :
- •Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
- •A male or female between, and including, 18 and 45 years at the time of the first vaccination.
- •Written informed consent obtained from the subject.
- •Healthy subjects as established by medical history, clinical examination and clinical laboratory assessment before entering into the study.
- •If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
- •Exclusion criteria:
- •The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
- •Previous vaccination against Hepatitis B.
- •Positive for anti-HBs antibodies, antiHBc antibodies, HBsAg, HCV antibodies and/or HIV.
- •Any previous administration of specific adjuvant components.
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the influenza vaccine (pandemic or seasonal) which can be administered > 21 days preceding or > 21 days following each primary vaccine dose (Doses 1 and 2) AND > 7 days preceding or > 7 days following the booster dose.
- •Administration of immunoglobulins and/or any blood products within the last 3 months.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
- •Current serious neurologic or mental disease.
- •Any past or current malignancies and lymphoproliferative disorders.
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal functional abnormality, autoimmune disease or anemia, as determined by physical examination or laboratory screening tests at the discretion of the investigator.
- •Acute disease at the time of enrolment.
- •Pregnant or lactating female.
- •History of chronic alcohol consumption and/or drug abuse.
- •Other conditions that the principal investigator judges may interfere with study findings.
排除标准
- 未提供
研究组 & 干预措施
GSK223192A 1 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 1, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: GSK Biologicals' Hepatitis B vaccines (GSK223192A) (Biological)
GSK223192A 1 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 1, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: HBsAg (Booster injection) (Biological)
GSK223192A 2 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 2, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: GSK Biologicals' Hepatitis B vaccines (GSK223192A) (Biological)
GSK223192A 2 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 2, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: HBsAg (Booster injection) (Biological)
GSK223192A 3 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 3, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: GSK Biologicals' Hepatitis B vaccines (GSK223192A) (Biological)
GSK223192A 3 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 3, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: HBsAg (Booster injection) (Biological)
Fendrix Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Fendrix™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Fendrix™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: Fendrix™ (Biological)
Fendrix Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Fendrix™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Fendrix™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: HBsAg (Booster injection) (Biological)
Engerix-B Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Engerix-B™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Engerix-B™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: Engerix-B™ (Biological)
Engerix-B Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Engerix-B™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Engerix-B™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
干预措施: HBsAg (Booster injection) (Biological)
结局指标
主要结局
Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells .
时间窗: At Day 44
The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD40L), Interleukin (IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs). Results for the Day 44 time point are the primary results among the outcome measure results presented.
次要结局
- Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells(At Days 0, 14, 30 and 60)
- Number of Hepatitis B (HB) - Specific Cluster of Differentiation 8 (CD8+) T Cells.(At Days 0, 14, 30, 44, and 60)
- Number of HB Specific CD4+ T Cells .(At Days 0, 180 and 360)
- Number of HB - Specific CD8+ T Cells.(At Days 0, 180 and 360)
- Number of HB Specific Cluster of Differentiation 4 (CD4+) T Cells Expressing Th1/Th2 Cytokine Profile(At Days 0 and 180)
- Number of HB - Specific CD4+ T Cells.(At Days 0, 360 and 374)
- Number of HB - Specific CD8+ T Cells(At Days 0, 14, 30, 44, 60 and 180)
- Number of HB - Specific CD4+ T Cells(At Days 0, 14, 30, 33, 37, 44 and 60)
- Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells Expressing T Helper Cell Type 1 Response/T Helper Cell Type 2 Response (Th1/Th2) Cytokine Profile(At Days 0, 14, 30, 44 and 60)
- Anti-Hepatitis B (Anti-HB) Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA)(At Days 0, 30, 44, and 60)
- Anti-HB Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA)(At Days 0, 180 and 360)
- Anti-HB Antibody Concentrations in Serum, as Measured by CLIA(At Days 0, 374 and 390)
- Number of HB-specific Memory B Cells(At Days 180 and 360)
- Number of Hepatitis B (HB)-Specific Memory B Cells(At Days 0, 30, 37, 44 and 60.)
- Normalized Levels of C-reactive Protein (CRP)(At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33 and 37.)
- Normalized Levels of WBC and of CPK(At Days 0, 30, 37 and 60.)
- Concentrations of the Interferon-gamma (IFN-g), Interleukin (IL)-1beta, IL-5, IL-6, IL-10, Tumor Necrosis Factor-alpha, IFN-g-inducible Protein-10 and Monocyte Chemotactic Protein-1 Cytokines in Serum(At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30,30+ (Day 30 + 3 to 6 hours), 31, 33 and 37.)
- Normalized Levels of White Blood Cells (WBC) and Creatine Phosphokinases (CPK)(At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60.)
- Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils(At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60.)
- Levels of WBC, NEU, LYM, MON, EOS and BAS(At Days 0, 30, 37 and 60.)
- Number of Subjects With Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase.(At Day 0 and up to Day 60.)
- Normalized Levels of CRP(At Days 0, 30 and 37.)
- Normalized Levels of Red Blood Cells and Platelets(At Days 0, 30, 37 and 60.)
- Number of Subjects Having Normal and Abnormal Levels of WBC, NEU, LYM, MON, EOS, BAS, CRP, and CPK.(At Days 360 and 390.)
- Number of Subjects With Normal and Abnormal Levels of Red Blood Cells, Platelets, Haemoglobin, Alanine Aminotransferase, Aspartate Aminotransferase, Serum Creatinine, Urea and Lactate Dehydrogenase(At Day 0 and up to Day 60.)
- Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Following Primary Vaccination.(Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine.)
- Normalized Levels of Haemoglobin, Alanine Aminotransferase and Aspartate Aminotransferase(At Days 0, 30, 37 and 60.)
- Normalized Levels of Serum Creatinine, Urea and Lactate Dehydrogenase(At Days 0, 30, 37 and 60.)
- Number of Subjects With Normal and Abnormal Levels of WBC, NEU, LYM, MON, EOS, BAS, CRP, and CPK.(At Day 0 and up to Day 60.)
- Number of Subjects Presenting Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase.(Post vaccination (up to Day 360))
- Number of Subjects With Normal and Abnormal Levels of RBC, PLA, HGB, ALT, AST, S-CREA, Urea and LDH(post vaccination (up to Day 360).)
- Number of Subjects Presenting Normal and Abnormal Levels of Red Blood Cells, Platelets, Haemoglobin, Alanine Aminotransferase, Aspartate Aminotransferase, Serum Creatinine, Urea and Lactate Dehydrogenase(At Days 360 and 390.)
- Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms Following Primary Vaccination.(Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccines.)
- Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms Following Booster Vaccination.(Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens)
- Number of Subjects Reporting Any, Grade 3 and/or Related Unsolicited Adverse Events (AEs) Following Primary Vaccination(Within the 31-day (Days 0-30) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine)
- Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Following Booster Vaccination.(Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens)
- Number of Subjects Reporting Any, Grade 3 and/or Related Unsolicited Adverse Events (AEs) Following Booster Vaccination(Within the 31-day (Days 0-30) follow up period following booster vaccination with HBsAg antigens)
- Number of Subjects Reporting Any and Related Adverse Events of Specific Interest (AESIs)(During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2.)
- Number of Subjects Reporting Any Serious Adverse Events (SAEs) and SAEs Related to Study Vaccination(During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2.)
- Levels of Messenger Ribonucleic Acid (mRNA) as Measured by Quantitative Polymerase Chain Reaction (qPCR)(At Days 0, 1, 14, 30, 31, 33 and 37)
- Messenger Ribonucleic Acid (mRNA) Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR)(At Days 0, 1, 14, 30, 31, 33 and 37)
- mRNA Levels as Measured by qPCR(At Days 0, 1, 14, 30, 31, 33 and 37)
- mRNA Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR)(At Days 0, 1, 14, 30, 31, 33 and 37)
- Levels of mRNA as Measured by qPCR(At Days 0, 1, 14, 30, 31, 33 and 37)
- Levels of Messenger Ribonucleic Acid (mRNA) as Measured by qPCR(At Days 0, 1, 14, 30, 31, 33 and 37)
- Levels of mRNA as Measured by Quantitative Polymerase Chain Reaction (qPCR)(At Days 0, 1, 14, 30, 31, 33 and 37)