Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™
2018年7月18日 更新者：GlaxoSmithKline
An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.
This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.
No new subjects will be recruited during this booster phase of the study.
研究概览
研究类型
介入性
注册 (实际的)
210
阶段
- 第四阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
12年 至 15年 (孩子)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Inclusion Criteria:
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
- A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study
- Written informed consent obtained from the subject.
All subjects must satisfy the following criteria at entry into the challenge dose phase:
- A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
- Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
- Written informed consent obtained from the subject.
- Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
- If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.
Exclusion Criteria:
The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.
- Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
- Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
- History of hepatitis A or hepatitis B infection.
- Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.
The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase:
- Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
- Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
- History of hepatitis A or hepatitis B infection.
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- Acute disease at the time of.
- Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
- Pregnant or lactating female.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Twinrix Adult Group
Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study
|
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
|
|
实验性的：Twinrix Junior Group
Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study
|
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Anti-HAV Antibody Concentrations
大体时间：At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
|
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HAV seropositive subjects.
Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
|
|
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
大体时间：At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
|
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL.
Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL).
The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
|
|
Anti-HBs Antibody Concentrations
大体时间：At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
|
Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA. |
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
|
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Anti-HBs Anamnestic Response.
大体时间：One month after the challenge dose.
|
Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points. |
One month after the challenge dose.
|
|
Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
大体时间：At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
|
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).
|
At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
大体时间：Since the last long-term follow-up visit up to Year 11.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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Since the last long-term follow-up visit up to Year 11.
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
大体时间：Since the last long-term follow-up visit up to Year 12.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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Since the last long-term follow-up visit up to Year 12.
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
大体时间：Since the last long-term follow-up visit up to Year 13.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 13.
|
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Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
大体时间：Since the last long-term follow-up visit up to Year 14.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 14.
|
|
Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
大体时间：Since the last long-term follow-up visit up to Year 15.
|
SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
|
Since the last long-term follow-up visit up to Year 15.
|
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Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
大体时间：Before (PRE) the challenge dose
|
Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL). Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose. |
Before (PRE) the challenge dose
|
|
Anti-HAV Antibody Concentrations
大体时间：Before (PRE) the challenge dose
|
Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HAV seropositive subjects.
Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.
|
Before (PRE) the challenge dose
|
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Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
大体时间：During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
|
Solicited local symptoms assessed were pain, redness and swelling.
Any = occurrence of the symptom regardless of intensity grade.
Grade 3 pain = pain that prevented normal activity.
Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
|
During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
|
|
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
大体时间：Before (PRE) and one month after (POST) the challenge dose
|
Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL
|
Before (PRE) and one month after (POST) the challenge dose
|
|
Anti-HBs Antibody Concentrations
大体时间：Before (PRE) and one month after (POST) the challenge dose
|
Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL.
The analysis was performed on anti-HBs seropositive subjects.
Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.
|
Before (PRE) and one month after (POST) the challenge dose
|
|
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
大体时间：During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
|
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever (axillary temperature).
Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain.
Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination.
Grade 3 symptoms = symptoms that prevented normal activity.
Grade 3 fever = axillary temperature > 39.5°C.
Related = general symptoms which were assessed by the investigator as causally related to vaccination.
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During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
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Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
大体时间：During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
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An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study.
Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Grade 3 = AE that prevented normal activity.
Related = AE assessed by the investigator as causally related to the study vaccination.
|
During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
|
|
Number of Subjects With Serious Adverse Events (SAEs).
大体时间：One month after the administration of the challenge dose (Month 0 to Month 1)
|
Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
|
One month after the administration of the challenge dose (Month 0 to Month 1)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Agrawal A, Kolhapure S, Andani A, Ota MOC, Badur S, Karkada N, Mitra M. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020 Dec;9(4):785-796. doi: 10.1007/s40121-020-00311-8. Epub 2020 Jul 24.
- Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 20.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年5月1日
初级完成 (实际的)
2014年7月1日
研究完成 (实际的)
2014年7月1日
研究注册日期
首次提交
2009年4月2日
首先提交符合 QC 标准的
2009年4月2日
首次发布 (估计)
2009年4月3日
研究记录更新
最后更新发布 (实际的)
2018年8月20日
上次提交的符合 QC 标准的更新
2018年7月18日
最后验证
2018年7月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 110699
- 110700 (其他标识符：GSK)
- 110701 (其他标识符：GSK)
- 110702 (其他标识符：GSK)
- 110703 (其他标识符：GSK)
- 110704 (其他标识符：GSK)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
研究数据/文件
-
研究协议
信息标识符：110699信息评论：For additional information about this study please refer to the GSK Clinical Study Register
-
个人参与者数据集
信息标识符：110699信息评论：For additional information about this study please refer to the GSK Clinical Study Register
-
临床研究报告
信息标识符：110699信息评论：For additional information about this study please refer to the GSK Clinical Study Register
-
数据集规范
信息标识符：110699信息评论：For additional information about this study please refer to the GSK Clinical Study Register
-
知情同意书
信息标识符：110699信息评论：For additional information about this study please refer to the GSK Clinical Study Register
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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