Phase III, Partially Double-blind Study to Evaluate Consistency and Immunogenicity of 3 Lots of GSK Biologicals' Hib Conjugate Vaccine 208108 Versus ActHIB and Pentacel at 2, 4, 6 and 15-18 Months of Age in Healthy Infants
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,003
- 试验地点
- 64
- 主要终点
- Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL
研究概览
简要总结
The purpose of this study is to evaluate safety, to demonstrate lot-to-lot consistency of the vaccine, to address the relevant concomitant vaccine administrations and to provide a comparison between GSK Biologicals' Hib conjugate vaccine and the licensed monovalent Hib vaccine ActHIB as well as the licensed combination product Pentacel in infants at 2, 4, 6 and 15-18 months of age. This study is designed with a primary and a booster phase.
详细描述
This protocol posting has been updated following protocol amendment 3, dated 12 April 2011. The impacted section is: Eligibility Criteria (Exclusion 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, Care Provider)
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
- •Subjects for whom the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol (e.g., completion of the diary card, return for follow-up visits).
- •A male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.
- •Written informed consent obtained from the subject's parent/LAR.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Born after a gestation period of minimum 36 weeks.
- •Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.
排除标准
- •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.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
- •Planned administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine and until 30 days after the booster dose.
- •Previous vaccination against Haemophilus influenzae type b, diphtheria, tetanus, pertussis, Pneumococcus, rotavirus and/or poliovirus; more than one previous dose of hepatitis B vaccine.
- •History of Haemophilus influenzae type b, diphtheria, tetanus, pertussis, pneumococcal, rotavirus, poliovirus, and hepatitis B diseases.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including dry natural latex rubber.
- •Major congenital defects or serious chronic illness.
- •History of any neurologic disorders or seizures.
- •Acute disease at time of enrollment. All vaccines can be administered to persons with a minor illness.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- •Concurrent participation in another clinical study, up to 30 days prior to study entry or at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
- •Child in care.
- •History of intussusception.
- •History of uncorrected congenital malformation of the gastrointestinal tract that would predispose the infant to intussusception.
- •History of Severe Combined Immunodeficiency Disease.
研究组 & 干预措施
Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: GSK Biologicals' Haemophilus influenzae type b vaccine (GSK 208108) (Biological)
Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Pediarix™ (Biological)
Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Prevnar 13™ (Biological)
Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Rotarix™ (Biological)
Hiberix Group
Pooled group of subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of 3 different lots of Hiberix® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age The Hiberix® vaccine was administered intramuscularly in the right thigh. Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Infanrix™ (Biological)
ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: ActHIB™ (Biological)
ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Pediarix™ (Biological)
ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Prevnar 13™ (Biological)
ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Rotarix™ (Biological)
ActHIB Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of ActHIB® vaccine co-administered with 3 doses of Pediarix® and Prevnar13® vaccines at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The ActHIB® vaccine was administered intramuscularly in the right thigh. The Pediarix® vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally.
干预措施: Infanrix™ (Biological)
Pentacel Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.
干预措施: Pentacel™ (Biological)
Pentacel Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.
干预措施: Prevnar 13™ (Biological)
Pentacel Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.
干预措施: Rotarix™ (Biological)
Pentacel Group
Subjects, male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination, who received 3 doses of Pentacel® vaccine co-administered with 3 doses of Prevnar13® vaccine, 2 or 3 doses of Engerix™-B vaccine at 2, 4 and 6 months of age and 2 doses of Rotarix® vaccine at 2 and 4 months of age. The Pentacel® vaccine was administered intramuscularly in the right thigh. The Engerix™-B vaccine was administered intramuscularly in the left thigh. The Prevnar13® vaccine was administered intramuscularly in the left thigh or deltoid. The Rotarix® vaccine was administered orally. If subjects in the Pentacel Group had received a birth dose of Hepatitis B vaccine then they were to receive Engerix™-B vaccine only at 2 and 6 months of age.
干预措施: Engerix™-B (Biological)
结局指标
主要结局
Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL
时间窗: At 1 month after last dose of primary vaccination
Non-inferiority of Hiberix to ActHIB, each co-administered with Pediarix, Prevnar13 and Rotarix following 3 primary doses in terms of immune response to PRP (Anti-PRP≥ 0.15 µ g/ml and ≥1.0 µg/mL).
Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibody Concentrations
时间窗: At 1 month after last dose of primary vaccination
Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.
Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations
时间窗: At 1 month after last dose of primary vaccination
Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).
Number of Subjects With Anti-Protein-D (Anti-D) and Anti-Protein-T (Anti-T) Antibody Concentrations ≥ 0.1 International Units Per Milliliter (IU/mL)
时间窗: At 1 month after last dose of primary vaccination
Non-inferiority of Pediarix co-administered with Hiberix, Prevnar13 and Rotarix compared to Pediarix co-administered with ActHIB, Prevnar13 and Rotarix following 3 primary vaccine doses in terms of immune response to Diphtheria, Tetanus.
Anti-Streptococcus Pneumoniae (S.Pneumoniae) Antibody Concentrations
时间窗: At 1 month after last dose of primary vaccination
Antibody concentrations against S.pneumoniae were given as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).
Number of Subjects With Seroresponse (95%) to Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA)
时间窗: At 1 month after last dose of primary vaccination
Seroresponse (95%) was defined as the number of subjects showing a concentration above a threshold that leads to 95% seroresponse in the ActHIB group.
Number of Subjects With Anti-Polio 1,2,3 Antibody Titres Greater Than or Equal to Cut-off Value
时间窗: At 1 month after last dose of primary vaccination
The cut-off value was defined as a concentration ≥ 8 ED50 (ED50 is the concentration at which the protein exhibits 50% of its maximum activity). The polio testing which started at the Biomnis laboratory was stopped because the polio virus micro-neutralization assays were found to be not in line with the quality standards defined in GSK Biologicals' SOPs. As a result, polio testing was restarted at the GSK laboratory and the results were uploaded into the clinical database.
Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 1.0 µg/mL
时间窗: At 1 month after booster vaccination
Non-inferiority of a booster dose of Hiberix co-administered with Infanrix in subjects 15-18 months of age who received 3 primary vaccine doses of Hiberix to a booster dose of ActHIB co-administered with Infanrix in subjects of 15-18 months of age who received 3 primary vaccine doses of ActHIB in terms of immune response to PRP
次要结局
- Number of Subjects With Anti-PT, Anti-PRN and Anti-FHA Antibody Concentrations ≥ 5 EL.U/mL(At 1 month after last dose of primary vaccination)
- Antibody Titers for Poliovirus Types 1, 2 and 3(At 1 month after last dose of primary vaccination)
- Anti-polyribosylribitol Phosphate (PRP) Antibody Concentrations(Prior to the booster vaccination and 1 month after the booster vaccination)
- Anti-protein-D (Anti-D) and Anti-protein-T (Anti-T) Antibody Concentrations(At 1 month after last dose of primary vaccination)
- Number of Subjects With Any Solicited Local Symptoms(Within 4 days (Days 0-3) following the booster dose)
- Anti-Hepatitis B (Anti-HBs) Antibody Concentrations(At 1 month after last dose of primary vaccination)
- Anti-Hepatitis B (Anti-HBs) Antibody Concentrations ≥10.0 mIU/mL and ≥6.2 mIU/mL(Prior to the booster vaccination)
- Number of Subjects With Anti-HB Antibody Concentrations ≥10.0 mlU/mL and ≥6.2mLU/mL(Prior to booster vaccination)
- Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ 5 EL.U/mL(Prior to the booster vaccination and 1 month after the booster vaccination)
- Number of Subjects With Any Solicited General Symptoms(Within 4 days (Days 0-3) following the booster dose)
- Number of Subjects With Any Unsolicited Adverse Events (AEs).(Within 31 days (Day 0 to Day 30) following the booster dose)
- Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL(Prior to the booster vaccination and 1 month after the booster vaccination)
- Number of Subjects With Anti-HBs Antibody Concentrations Greater Than or Equal to Cut-off Values(At 1 month after last dose of primary vaccination)
- Number of Subjects With AEs of Specific Interest (AESIs)(From booster dose until 6 months following receipt of the booster dose)
- Number of Subjects With Seroresponse (90%) to Anti-PT, Anti-PRN and Anti-FHA(At 1 month after last dose of primary vaccination)
- Anti-poliovirus Types 1, 2, and 3 Antibody Titres and Titres ≥ 8(Prior to the booster vaccination)
- Number of Subjects With Serious Adverse Events (SAEs)(From the booster dose until 6 months following receipt of the booster dose)
- Number of Subjects With S.Pneumoniae Antibody Concentrations ≥ 0.05 µg/mL, ≥ 0.2 µg/mL and ≥1.0 µg/mL(At 1 month after the last dose of primary vaccination)
- Number of Subjects With Anti-Polio-1,2,3 Antibody Titers ≥ 8(Prior to booster vaccination)
- Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥1.0 IU/mL, Respectively.(Prior to the booster vaccination and 1 month after the booster vaccination)
- Anti-FHA, Anti-PRN and Anti-PT Antibody Concentrations(pre-booster and one month after booster vaccination)