Persistence Study of GSK Biologicals' Tdap Vaccine (776423), 1, 3, 5 and 9 Years Following Administration as a Single Dose in NCT00346073 Study and to Evaluate the Immunogenicity and Safety of Boostrix as a Second Dose of Tdap, When Administered at Year 9
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,954
- 试验地点
- 38
- 主要终点
- Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Greater Than or Equal to (≥) Protocol Specified Cut-off
研究概览
简要总结
The purpose of this study is to evaluate the persistence of antibodies against all the vaccine antigens 1, 3, 5 and 9 years after an initial vaccination with Tdap, and also to assess immunogenicity and safety of another dose of Boostrix, administered in this study.
This protocol posting deals with objectives and outcome measures of the extension phase. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00346073).
详细描述
Subjects were previously vaccinated with either Boostrix or a control Tdap vaccine (Sanofi Pasteurs' Adacel) in study NCT00346073. Only subjects who were part of the primary study will be invited to participate in this study. All subjects will receive a single dose of Boostrix at Visit 6 (Day 0) and subjects will be observed till Visit 7 (Day 30) for safety in terms of solicited adverse events (during 4 days post vaccination), unsolicited adverse events (during 31 days post vaccination) and serious adverse event (during the trial period). A blood sample will be collected from all subjects before vaccination (Visit 6) and one month after vaccination (Visit 7) for antibodies estimation.
This summary has been updated following Protocol amendment 1 dated 09 November 2010, amendment 2 dated 18 February 2014, and amendment 3 dated 10 December 2014. The protocol was amended first due to the following reasons:
- The maximum window period allowed for the return of subjects for the Year 5 and Year 10 follow-up visits (Visit 5 and Visit 6) was extended from ± 5 weeks to ± 8 weeks.
- The contact details for reporting of SAEs were clarified.
- Text pertaining to the reporting of spontaneous abortion was removed from the protocol.
- The number of attempts to contact subjects who did not return for scheduled persistence visits was clarified.
The main purpose of protocol amendment 2 is to evaluate the immunogenicity and safety of Boostrix as a second dose of Tdap vaccine when administered 8 years after an initial dose of Tdap. The Year 10 time point for evaluation of persistence has been cancelled because it is no longer feasible to conduct after a second dose of Tdap vaccine has been administered at Year 8.
The purpose of amendment 3 is to add co-primary objective to demonstrate that the immune response elicited by a second dose of Tdap vaccine, Boostrix (Boostrix group and Adacel group) is non-inferior to the immune response elicited by a first dose of Tdap vaccine (Control group), with respect to booster response against diphtheria, tetanus and pertussis (PT, FHA and PRN) antigens, one month following vaccination according to CBER's input. Accordingly, the study start has been pushed to Year 9 and this is reflected throughout the document.
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
- None
入排标准
- 年龄范围
- 28 Years 至 73 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Persistence follow-up phase up to Year 9 time point:
- •The following criteria are applicable to subjects who refuse vaccination at Year 8 time point:
- •All subjects who received study vaccination (Boostrix or Adacel) in study NCT00346073 will be considered eligible to participate in this study.
- •Written informed consent must be obtained from the subject prior to each study time point.
- •Vaccination phase at Year 9 applicable for subjects in Boostrix and Adacel groups only:
- •The following criterion is applicable to subjects willing to consent to vaccination at Year 9 time point in the Boostrix and Adacel groups:
- •All subjects who received study vaccination (Boostrix or Adacel) in study NCT00346073 will be considered eligible to participate in this study.
- •Vaccination phase at Year 9 applicable for subjects in the Control group only:
- •The following criterion is applicable to subjects willing to consent to vaccination at Year 9 time point in the Control group only:
- •Subjects within the age range of 28-73 years will be considered eligible to participate in this study in the Control group.
- •Vaccination phase at Year 9 applicable for ALL subjects (Control, Boostrix and Adacel groups):
- •The following criteria are applicable to subjects willing to consent to vaccination at Year 9 time point in the Boostrix, Adacel and Control groups:
- •All subjects must satisfy the following criteria at study entry at Year 9 time point:
- •Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
- •Written informed consent obtained from the subject for vaccination at Year 9 time point.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Female subjects of non-childbearing potential may be enrolled in the study.
- •Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
- •Female subjects of child bearing potential may be enrolled in the study, if the subject
- •has practiced adequate contraception for 30 days prior to vaccination, and
- •has a negative pregnancy test on the day of vaccination, and
- •has agreed to continue adequate contraception for 1 month after completion of the vaccine dose
排除标准
- •The following criteria should be checked at the time of Year 9 vaccination time point. If any criteria is applicable, the subject must not be vaccinated in the study:
- •For subjects in Boostrix and Adacel groups:
- •Administration of Tdap vaccine since the last dose received in the study NCT
- •For subjects in the Control group:
- •Administration of Tdap (Boostrix or Adacel) vaccine at any time prior to the administration of Boostrix vaccine in this study.
- •For ALL subjects (Control, Boostrix and Adacel groups):
- •Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period, 31 days (Day 0-30).
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to Visit 6 (pre-vacc). Inhaled and topical steroids are allowed.
- •Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of vaccine, with the exception of inactivated Influenza vaccine which is allowed throughout the study period, 31 days (Day 0-30).
- •- Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
- •Hypersensitivity to latex.
- •History of diphtheria, tetanus or pertussis diseases.
- •Severe allergic reaction (e.g. anaphylaxis) after previous administration of any tetanus toxoid, diphtheria toxoid, or pertussis-antigen containing vaccines, or any component of Boostrix.
- •History of any neurological disorders or seizures.
- •Encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) of unknown etiology occurring within seven days following previous vaccination with pertussis-containing vaccine.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •Acute disease and/or fever at the time of enrolment.
- •Fever is defined as temperature ≥ 100.4°F by any route. The preferred route for recording temperature in this study will be oral.
- •Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
- •Administration of immunoglobulins and/or any blood products within three months preceding the dose of study vaccine or planned administration during the study period, 31 days (Day 0-30).
- •Administration of any tetanus or diphtheria containing vaccine or any registered or investigational vaccine utilizing a diphtheria toxoid or tetanus toxoid carrier within 5 years prior to the administration of Boostrix vaccine in this study.
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- •Pregnant or lactating female.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions during the 31 day (Day 0-30) follow-up period post-vaccination.
结局指标
主要结局
Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Greater Than or Equal to (≥) Protocol Specified Cut-off
时间窗: At year 1 after the vaccination in primary study (NCT00346073)
Anti-D cut-off was defined as ≥ 0.1 International Units per milliliter (IU/mL) determined with Enzyme-linked Immunosorbent Assay (ELISA)
Number of Subjects With Anti-tetanus (Anti-T) Antibody Concentrations ≥ Protocol Specified Cut-off
时间窗: At year 1 after the vaccination in primary study (NCT00346073)
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off
时间窗: At Year 9, one month before the booster vaccination.
Anti-D cut-off was defined as ≥ to 0.1IU/mL as assessed by ELISA.
Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off
时间窗: At Year 9, one month before the booster vaccination.
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-D and Anti-T Concentrations ≥ 0.1 IU/mL and 1 IU/mL
时间窗: At Year 9, one month after the booster vaccination.
Number of subjects with anti-D and anti-T concentrations ≥ 0.1 IU/mL and 1 IU/mL were tabulated
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
时间窗: At Year 9, one month after the booster vaccination
Anti-PT, anti-FHA and anti-PRN antibody concentrations were measured by ELISA, tabulated as GMCs and expressed in IU/mL.
Booster Response to D and T Antigens
时间窗: At Year 9, one month after the booster vaccination.
A booster response was defined as: for initially seronegative subjects (S-) (pre-vaccination concentration below cut-off: \< 0.1 IU/mL) antibody concentrations at least four times the cut-off (post vaccination concentration ≥ 0.4 IU/mL); for initially seropositive subjects (S+) (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration; Total = subjects either seropositive or seronegative.
Booster Response to PT, FHA and PRN Antigens
时间窗: At Year 9, one month after the booster vaccination.
Booster response was defined as: for subjects with pre-vaccination antibody concentration \< 5 EL.U/mL (S-): antibody concentration ≥ 20 EL.U/mL; for subjects with pre-vaccination antibody concentration ≥ 5 EL.U/mL and \< 20 EL.U/mL (S+, \<4\*cut-off): antibody concentration at least four times the pre-vaccination concentration; for subjects with pre-vaccination antibody concentration ≥ 20 EL.U/mL (S+, ≥4\*cut-off): antibody concentration at least two times the pre-vaccination concentration; Total = subjects either seropositive or seronegative
次要结局
- Number of Subjects With Anti-PRN Antibody Concentrations Equal to or Above Protocol Specified Cut-off(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Number of Subjects With Anti-pertussis Toxoid (PT) Antibody Concentrations Equal to or Above Protocol Specified Cut-off(At 1, 3, and 5 years after the vaccination in primary study (NCT00346073))
- Number of Subjects With Anti-PT Antibody Concentrations Equal to or Above Protocol Specified Cut-off(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Anti-D Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Anti-PT Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Number of Subjects With Anti-FHA Antibody Concentrations Equal to or Above Protocol Specified Cut-off(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Seroprotection Status for Anti-D Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms - Year 9(During the 4-day (Days 0-3) post vaccination period.)
- Anti-T Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Anti-PRN Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Alternative Booster Responses to Anti-PT, Anti-FHA and Anti-PRN Antigens(At Year 9, one month after booster vaccination)
- Anti-FHA Antibody Concentration(At Year 9, one month before(pre booster) and after the booster vaccination(post booster))
- Alternative Booster Response to Anti-D and Anti-T Antigens(At Year 9, one month after booster vaccination)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Year 9(During the 4-day (Days 0-3) post vaccination period.)
- Number of Subjects With Any Large Injection Site Reaction - Year 9(During the 4-day (Days 0-3) follow-up period after vaccination.)
- Number of Subjects With Any Unsolicited Adverse Events (AEs) - Year 9(During the 31-day (Days 0-30) post-vaccination period.)
- Number of Subjects With Serious Adverse Events (SAEs) - Year 9(During the 31-day (Days 0-30) post-vaccination period)