A Phase II, Open (Partially Double-blind), Randomised, Controlled, Multicentre, Primary Vaccination Study to Evaluate the Immunogenicity (Including Immune Memory), Reactogenicity and Safety of Three Different Formulations of the GSK Biologicals' Combined Haemophilus Influenzae Type B-meningococcal Serogroups CY Conjugate Vaccine Given Concomitantly With Infanrix® Penta and Prevenar®, Versus ActHIB® and Meningitec® Given Concomitantly With Infanrix® Penta and Versus ActHIB® Given Concomitantly With Infanrix® Penta and Prevenar® in Infants According to a 2-4-6 Month Schedule.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 409
- 试验地点
- 3
- 主要终点
- Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers Greater Than or Equal to 1:8
研究概览
简要总结
This study evaluated the safety and immunogenicity of 3 formulations of Hib-MenCY-TT vaccine compared to 2 control groups receiving licensed meningococcal serogroup C conjugate vaccine and/or licensed Hib conjugate vaccine administered at 2, 4, and 6 months of age. Antibody persistence and immune responses to polysaccharide vaccine boosters were additionally assessed at 11 to 14 months of age.
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Weeks 至 12 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
- •Written informed consent obtained from the parent or guardian of the subject.
- •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- •Vaccinated against hepatitis B at birth.
- •Born after a gestation period of 36 - 42 weeks.
排除标准
- •Use of any investigational or non-registered 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.
- •Chronic administration of immunosuppressants or other immune-modifying drugs since birth
- •Any chronic drug therapy to be continued during the study period.
- •Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the first dose of vaccine(s).
- •Previous vaccination against diphtheria, tetanus, pertussis, polio, N. meningitidis of serogroups C and Y, Haemophilus influenzae type b or Streptococcus pneumoniae.
- •History of or known exposure to diphtheria, tetanus, pertussis, polio, or invasive diseases due to N. meningitidis of serogroups C and Y, Haemophilus influenzae type b or Streptococcus pneumoniae.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
- •A family history of congenital or hereditary immunodeficiency.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- •Major congenital defects or serious chronic illness.
- •History of any neurologic disorders or seizures.
- •Acute disease at the time of enrolment.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
研究组 & 干预措施
MenHibrix Formulation 2 Group
Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Infanrix® Penta (Biological)
MenHibrix Formulation 1 Group
Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Hib-MenCY-TT vaccine (MenHibrix) (Biological)
MenHibrix Formulation 1 Group
Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Infanrix® Penta (Biological)
MenHibrix Formulation 1 Group
Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Prevenar® (Biological)
MenHibrix Formulation 1 Group
Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Mencevax® ACWY (Biological)
MenHibrix Formulation 1 Group
Subjects were primed with MenHibrix formulation 1 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: PRP (Polyribosyl Ribitol Phosphate) (Biological)
MenHibrix Formulation 2 Group
Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Hib-MenCY-TT vaccine (MenHibrix) (Biological)
MenHibrix Formulation 2 Group
Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Prevenar® (Biological)
MenHibrix Formulation 2 Group
Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Mencevax® ACWY (Biological)
MenHibrix Formulation 2 Group
Subjects were primed with MenHibrix formulation 2 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: PRP (Polyribosyl Ribitol Phosphate) (Biological)
MenHibrix Formulation 3 Group
Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Hib-MenCY-TT vaccine (MenHibrix) (Biological)
MenHibrix Formulation 3 Group
Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Infanrix® Penta (Biological)
MenHibrix Formulation 3 Group
Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Prevenar® (Biological)
MenHibrix Formulation 3 Group
Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Mencevax® ACWY (Biological)
MenHibrix Formulation 3 Group
Subjects were primed with MenHibrix formulation 3 co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: PRP (Polyribosyl Ribitol Phosphate) (Biological)
Menjugate Group
Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Meningitec® (Biological)
Menjugate Group
Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: ActHIB® (Biological)
Menjugate Group
Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Infanrix® Penta (Biological)
Menjugate Group
Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Mencevax® ACWY (Biological)
Menjugate Group
Subjects were primed with Menjugate co-administered with Infanrix Penta and ActiHIB according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: PRP (Polyribosyl Ribitol Phosphate) (Biological)
ActHIB Group
Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: ActHIB® (Biological)
ActHIB Group
Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Infanrix® Penta (Biological)
ActHIB Group
Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Prevenar® (Biological)
ActHIB Group
Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: Mencevax® ACWY (Biological)
ActHIB Group
Subjects were primed with ActHIB co-administered with Infanrix Penta and Prevenar according to a 2-4-6 months of age schedule, and received a polysaccharide challenge dose (1/5th dose of MenACWY polysaccharide vaccine co-administered with 10 µg dose of plain PRP) at 12 months of age.
干预措施: PRP (Polyribosyl Ribitol Phosphate) (Biological)
结局指标
主要结局
Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers Greater Than or Equal to 1:8
时间窗: One month after primary vaccination (Month 5)
The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.
Number of Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to 1 Milligram Per Milliliter
时间窗: One month after primary vaccination (Month 5)
The cut-off concentration assessed was 1 milligram per milliliter (mg/mL).
Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers Greater Than or Equal to 1:8
时间窗: One month after primary vaccination (Month 5)
The cut-off titer assessed was a dilution of 1:8. Titers were expressed as the reciprocal of the dilution resulting in 50 percent inhibition.
次要结局
- Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Anti-polysaccharide C (PSC) Antibody Concentration(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Anti-tetanus Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup Y (MenY) Titers(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Anti-polysaccharide Y (PSY) Antibody Concentration(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Anti-diphtheria Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects With Serum Bactericidal Activity Using Baby Rabbit Complement (rSBA)- Neisseria Meningitidis Serogroup C (MenC) Titers Greater Than or Equal to 1:8(Prior to vaccination (Day 0), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects With rSBA-MenY Titers Greater Than or Equal to 1:8(Prior to vaccination (Day 0), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects With Anti-polysaccharide Y (PSY) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Anti-PRP Antibody Concentration(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects Seroprotected for Anti-diphtheria Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Seroseropositive for Anti-filamentus Haemagglutinin (FHA) Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Seroseropositive for Anti-pertactin (PRN) Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects With Anti-polysaccharide C (PSC) Antibody Concentration Greater Than or Equal to 30 Micrograms Per Milliliter (µg/mL)(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5), before administration of the polysaccharide challenge dose (Month 10) and one month after administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects Seroprotected for Anti-tetanus Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Anti- PT Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Course(During the 8-Day (Day 0-7) follow-up period after any vaccine dose during the primary vaccination course)
- Anti- FHA Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Reporting Solicited Local and General Symptoms After Administration of the Polysaccharide Challenge Dose(During the 8-Day (Day 0-7) follow-up period after the polysaccharide challenge dose)
- Number of Subjects Reporting Serious Adverse Events During the Primary Vaccination Course(Up to one month after the 3-dose primary vaccination course (Month 5))
- Anti-PRN Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Seroseropositive for Anti-pertussis Toxoid (PT) Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Anti-poliovirus Types 1, 2 and 3 Antibody Titers(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Anti-pneumococcal Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Reporting Unsolicited Adverse Events During the Primary Vaccination Course(During the 31-Day (Day 0-30) follow-up period after any vaccine dose during the primary vaccination course)
- Number of Subjects Reporting Unsolicited Adverse Events After Administration of the Polysaccharide Challenge Dose(During the 31-Day (Day 0-30) follow-up period after administration of the polysaccharide challenge dose)
- Number of Subjects Reporting Serious Adverse Events After Administration of the Polysaccharide Challenge Dose(Up to one month following administration of the polysaccharide challenge dose (Month 11))
- Number of Subjects Seroprotected for Anti-hepatitis B (HBs) Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Anti- HBs Antibody Concentrations(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects Seroprotected for Anti-poliovirus Types 1, 2 and 3 Antibodies(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))
- Number of Subjects With Anti-pneumococcal Antibody Concentrations Greater Than or Equal to Pre-defined Cut-off Values(Prior to vaccination (Day 0), one month after the 3-dose primary vaccination course (Month 5) and before administration of the polysaccharide challenge dose (Month 10))