Lot-to-Lot Consistency, Non-Inferiority Versus Mencevax™ and Evaluation of the Co-Administration With Fluarix™ of GSK Biologicals' Meningococcal Vaccine GSK134612, in Healthy Subjects Aged 18 Through 55 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,352
- 试验地点
- 4
- 主要终点
- Serum Bactericidal Assay (Performed Using Baby Rabbit Complement) for Neisseria Meningitidis Serogroups A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibody Titers, in Each of the 3 Lot Groups.
研究概览
简要总结
The purpose of this study is to demonstrate, in 18-55 year old adults, the consistency of different manufactured lots of meningococcal vaccine GSK134612, the non-inferiority of GSK134612 compared to licensed meningococcal vaccine Mencevax™, the non-inferiority of GSK134612 when given in an experimental co-administration with Fluarix™ compared to GSK134612 given alone and the immunogenicity of GSK134612 given with Fluarix™.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
详细描述
Multicentre study with 5 treatment groups. Three groups will receive three different manufactured lots of GSK134612, one group will receive one lot of GSK134612 given in an experimental co-administration with Fluarix™, the control group will receive Mencevax™. The study will be conducted in a double-blind manner with respect to the 3 lots of GSK134612 vaccine. The study will be 'open' between the groups receiving GSK134612 and the group receiving GSK134612 + Fluarix™ and the Mencevax™ group.
Each subject will have 2 blood samples taken for immunogenicity analyses, one prior to vaccination and one taken 30 days later.
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
- 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
- 是
入选标准
- •For all subjects:
- •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 55 years of age at the time of the vaccination.
- •Written informed consent obtained from the subject.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Previously completed routine childhood vaccinations to the best of his/her knowledge.
- •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.
排除标准
- •For all subjects:
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose.
- •Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine(s).
- •Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W, and/or Y within the last five previous years.
- •Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W, and/or Y.
- •Previous vaccination with tetanus toxoid within the last month.
- •History of meningococcal disease.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
- •A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
- •History of reactions or allergic disease likely to be exacerbated by any component of the vaccine.
- •Major congenital defects or serious chronic illness.
- •Acute disease at the time of enrolment.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
- •Pregnant or lactating female.
- •History of chronic alcohol consumption and/or drug abuse.
- •Female planning to become pregnant or planning to discontinue contraceptive precautions.
- •Additional criteria for subjects receiving Fluarix™ co-administration:
- •History of hypersensitivity to a previous dose of influenza vaccine.
- •History of reactions or allergy likely to be exacerbated by any component of the vaccine including egg, chicken protein, formaldehyde, thimerosal, gentamicin sulfate, or sodium deoxycholate.
- •History of administration of an influenza vaccine outside of this study, during current flu season.
研究组 & 干预措施
Nimenrix A Group
subjects received 1 dose of Nimenrix™ Lot A at Month 0. Nimenrix™ vaccine was administered by intramuscular injection in the deltoid region of the non-dominant arm.
干预措施: Meningococcal vaccine GSK134612 (Biological)
Nimenrix B Group
subjects received 1 dose of Nimenrix™ Lot B at Month 0. Nimenrix™ vaccine was administered by intramuscular injection in the deltoid region of the non-dominant arm.
干预措施: Meningococcal vaccine GSK134612 (Biological)
Nimenrix C Group
subjects received 1 dose of Nimenrix™ Lot C at Month 0. Nimenrix™ vaccine was administered by intramuscular injection in the deltoid region of the non-dominant arm.
干预措施: Meningococcal vaccine GSK134612 (Biological)
Mencevax ACWY Group
subjects received 1 dose of Mencevax™ ACWY vaccine at Month 0. Mencevax™ ACWY vaccine was administered by subcutaneous injection in the non-dominant upper arm.
干预措施: Mencevax™ACWY (Biological)
Nimenrix+Fluarix Group
subjects received 1 dose of Nimenrix™ Lot A co-administered with Fluarix™ vaccines at Month 0. Nimenrix™ vaccine was administered by intramuscular injection in the deltoid region of the non-dominant arm. Fluarix™ vaccine was administered by intramuscular injection in the deltoid region of the dominant arm.
干预措施: Meningococcal vaccine GSK134612 (Biological)
Nimenrix+Fluarix Group
subjects received 1 dose of Nimenrix™ Lot A co-administered with Fluarix™ vaccines at Month 0. Nimenrix™ vaccine was administered by intramuscular injection in the deltoid region of the non-dominant arm. Fluarix™ vaccine was administered by intramuscular injection in the deltoid region of the dominant arm.
干预措施: Fluarix™ (Biological)
结局指标
主要结局
Serum Bactericidal Assay (Performed Using Baby Rabbit Complement) for Neisseria Meningitidis Serogroups A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibody Titers, in Each of the 3 Lot Groups.
时间窗: One month after vaccination (at Month 1)
Titers were expressed as geometric mean antibody titers and were calculated on all subjects from both cohorts receiving 1 dose of Nimenrix vaccine lot A, B or C.
Number of Subjects With a Vaccine Response for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.
时间窗: One month after vaccination (at Month 1)
Vaccine response was defined as a rSBA titer of at least 1:32 in initially seronegative subjects (\<1:8) and as 4-fold increase in titer in initially seropositive subjects (≥1:8). A seronegative subject had antibody titer below 1:8 prior to vaccination and a seropositive subject had antibody titer equal to or above 1:8 prior to vaccination. Vaccine response was assessed for subjects of both cohorts receiving the Nimenrix vaccine (lot A without co-administration of Fluarix vaccine, lot B and lot C) or the Mencevax ACWY vaccine.
Serum Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 3 Influenza Virus Strains, in Subjects Receiving the Fluarix Vaccine.
时间窗: Prior to and one month after vaccination (at Month 0 and Month 1).
Titers were expressed as geometric mean antibody titers and were calculated on all subjects receiving 1 dose of Fluarix vaccine in the Flu vaccine cohort. The 3 influenza virus strains represented in the vaccine were A/H1N1, A/H3N2, and B.
Seroconversion Factor for HI Antibody Titers for Each of the 3 Influenza Virus Strains, in Subjects Receiving the Fluarix Vaccine.
时间窗: One month after vaccination (at Month 1)
Conversion factor defined as the fold increase in serum HI Geometric Mean Titers 1 month after vaccination compared to pre-vaccination, for each vaccine strain. Conversion factor was calculated on all subjects receiving 1 dose of Fluarix vaccine in the Flu vaccine cohort. The 3 influenza virus strains represented in the vaccine were A/H1N1, A/H3N2, and B.
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers, in Subjects Receiving the Nimenrix Lot A + Fluarix Vaccines or the Nimenrix Vaccine (Pooled Lots in the Flu Vaccine Cohort)
时间窗: One month after vaccination (at Month 1)
Titers were expressed as geometric mean antibody titers and were calculated on all subjects receiving 1 dose of Nimenrix vaccine lot A co-administered with Fluarix vaccine and on subjects receiving 1 dose of Nimenrix vaccine among all the manufactured lots (pooled groups from the Flu vaccine cohort).
Number of Seroconverted Subjects for HI Antibody Titers for Each of the 3 Influenza Virus Strains, in Subjects Receiving the Fluarix Vaccine.
时间窗: One month after vaccination (at Month 1)
Seroconversion was defined as the percentage of subjects with either a pre-vaccination HI titer \<1:10 and a post-vaccination titer \>1:40, or a pre-vaccination titer \>1:10 and a minimum 4-fold increase at post-vaccination titer, for each vaccine strain. Seroconversion was calculated on all subjects receiving 1 dose of Fluarix vaccine in the Flu vaccine cohort. The 3 influenza virus strains represented in the vaccine were A/H1N1, A/H3N2, and B.
Number of Seroprotected Subjects HI Antibody Titers for Each of the 3 Influenza Virus Strains, in Subjects Receiving the Fluarix Vaccine.
时间窗: Prior to and one month after vaccination (at Month 0 and Month 1)
Seroprotection was defined as the percentage of subjects with a serum HI titer ≥ 1:40 after vaccination (for each vaccine strain) that usually is accepted as indicating protection. Seroprotection was calculated on all subjects receiving 1 dose of Fluarix vaccine in the Flu vaccine cohort. The 3 influenza virus strains represented in the vaccine were A/H1N1, A/H3N2, and B.
次要结局
- Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Titers Equal to or Above the Cut-off Values, in Each of the 3 Lot Groups.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Antibody Titers, in Each of the 3 Lot Groups.(Prior to vaccination (at Month 0).)
- rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Antibody Titers, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With Anti-tetanus Antibody Concentrations Equal to or Above the Cut-off Value of 0.1 International Unit Per Milliliter (IU/mL), for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With Anti-meningococcal Polysaccharide Serogroups, A, C, W-135 and Y Antibody Concentrations Equal to or Above the Cut-off Values, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With Any and Severe Solicited Local Symptoms, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(During the 4-day (Days 0-3) follow-up period after vaccination)
- Number of Subjects With Any and Severe Solicited Local Symptoms, for Subjects in the Flu Vaccine Cohort Receiving the Nimenrix or the Mencevax ACWY Vaccines.(During the 4-day (Days 0-3) follow-up period after meningococcal vaccination)
- Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Titers Equal to or Above the Cut-off Values, for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Antibody Titers, for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY Titers Equal to or Above the Cut-off Values, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With a Vaccine Response for rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody, for Subjects in the Flu Vaccine Cohort(One month after vaccination (at Month 1))
- Number of Subjects With Anti-tetanus Antibody Concentrations Equal to or Above the Cut-off Value of 0.1 International Unit Per Milliliter (IU/mL), in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Anti-tetanus Antibody Concentrations for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 & Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values, for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Anti-tetanus Antibody Concentrations, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Anti-PSA, Anti-PSC, Anti-PSW-135 & Anti-PSY Antibody Concentrations, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCIs), for Subjects in the Flu Vaccine Cohort(From Dose 1 (at Month 0) up to study end (at Month 6))
- Anti-PSA, Anti-PSC, Anti-PSW-135 & Anti-PSY Antibody Concentrations, for Subjects in the Flu Vaccine Cohort(Prior to and one month after vaccination (at Month 0 and Month 1).)
- Number of Subjects With Any and Severe Solicited Local Symptoms, in Subjects Receiving the Fluarix Vaccine(During the 4-day (Days 0-3) follow-up period after Fluarix vaccine administration)
- Number of Subjects With Any and Severe Solicited General Symptoms, for Subjects in the Flu Vaccine Cohort(During the 4-day (Days 0-3) follow-up period after vaccination)
- Number of Subjects Reporting Rash, for Subjects in the Flu Vaccine Cohort(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Unsolicited Adverse Events (AEs), for Subjects in the Flu Vaccine Cohort(From Dose 1 (at Month 0) up to 1 month after vaccination (at Month 1))
- Number of Subjects With Any and Severe Solicited General Symptoms, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(During the 4-day (Days 0-3) follow-up period after vaccination)
- Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCIs), in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Unsolicited Adverse Events (AEs), in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(From Dose 1 (at Month 0) up to 1 month after vaccination (at Month 1))
- Number of Subjects Reporting Serious Adverse Events (SAEs), in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Rash, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Adverse Events (AEs) Resulting in Emergency Room (ER) Visits, in Subjects Receiving the Nimenrix (From the 3 Manufactured Lots Pooled) or the Mencevax ACWY Vaccines.(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Adverse Events (AEs) Resulting in Emergency Room (ER) Visits, for Subjects in the Flu Vaccine Cohort(From Dose 1 (at Month 0) up to study end (at Month 6))
- Number of Subjects Reporting Serious Adverse Events (SAEs), for Subjects in the Flu Vaccine Cohort(From Dose 1 (at Month 0) up to study end (at Month 6))