Safety, Immunogenicity and Consistency of 3 Manufacturing Lots of DTaP-IPV Vaccine Versus Separate Injections of GSK Biologicals' DTaP + Aventis Pasteur's IPV Administered as Booster Doses to Healthy Children 4-6 Years, Each Co-administered With Merck's MMR Vaccine
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,209
- 试验地点
- 24
- 主要终点
- Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects
研究概览
简要总结
The aims of this trial are to demonstrate the consistency of three manufacturing lots of GSK Biologicals' DTaP-IPV candidate vaccine in terms of immunogenicity and to evaluate the non-inferiority of GSK Biologicals' DTaP-IPV vaccine with respect to immunogenicity and safety compared to the control vaccines (separate injections of GSK Biologicals' DTaP vaccine [Infanrix] and Aventis Pasteur's IPV vaccine [IPOL]) when administered as a 5th dose of DTaP and a 4th dose of inactivated poliovirus vaccine in subjects 4 to 6 years of age. Vaccines will be co-administered with the second dose of M-M-RII, which is recommended at this age. Concomitant administration of a US-licensed influenza vaccine will be allowed according to seasonal availability of vaccine and at the discretion of the investigator.
详细描述
- Investigational groups: 3, each receive one of 3 lots of DTaP-IPV vaccine.
- Control: US-licensed DTaP (Infanrix) + US-licensed IPV (IPOL) vaccines administered in separate injections.
- Two study visits one month apart for a subset of subjects (Safety and Immunogenicity subset) with a blood draw at each visit. All other subjects will have one visit.
- A telephone contact 4-6 days after vaccination for all subjects, a telephone contact 31-38 days after vaccination for the Safety only subset and a telephone contact for all subjects during the extended safety follow-up phase (5 months following the active phase).
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
盲法说明
The study was conducted in an open manner except for the consistency lots of SB213503 vaccine that were double-blinded.
入排标准
- 年龄范围
- 4 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female child between and including 4 and 6 years of age at the time of vaccination.
- •Free of obvious health problems as established by medical history and brief medical evaluation before entering into the study.
- •Received 4 doses of Infanrix and 3 doses of IPOL during the first 2 years of life.
- •Vaccination against measles, mumps, and rubella in the second year of life.
- •Subjects whom the investigator believed would comply with the requirements of the protocol.
- •Written informed consent obtained before study entry from the parent(s) or guardian(s) of the subject.
排除标准
- •Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the administration of study vaccines, or planned use during the study period.
- •History of previous or intercurrent diphtheria, tetanus, pertussis, polio, measles, mumps, or rubella disease, or of vaccination against these diseases given after the second year of life.
- •Known exposure to diphtheria, tetanus, pertussis, or polio, prior to vaccination.
- •Poliovirus vaccination with one or more doses of OPV vaccine.
- •Administration or planned administration of a vaccine not foreseen by the study protocol within 30 days of study vaccination and ending at Day
- •Chronic administration or administration of immunosuppressants or other immune modifying drugs within six months prior to study vaccination or planned administration during the study period ending at Day
- •Administration of immunoglobulins and/or any blood products within three months prior to study vaccination or planned administration during the study period ending at Day
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
- •History of seizures or progressive neurological disorder, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy.
- •Major congenital defects or serious chronic illness.
- •Acute disease at the time of enrollment.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including allergic reactions to 2-phenoxyethanol, formaldehyde, neomycin, polymyxin B, streptomycin, gelatin, and/or latex.
- •History of anaphylactic reaction to egg proteins or previous doses of the vaccine(s).
- •Encephalopathy within 7 days of administration of previous dose of Infanrix.
- •Fever ≥ 40.5°C or 104.9°F (rectal temperature) (39.5°C or 103.1°F, oral/axillary) within 48 hours of previous dose of Infanrix not due to another identifiable cause.
- •Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of previous dose of Infanrix.
- •Persistent, severe, inconsolable screaming or crying lasting ≥ 3 hours which occurred within 48 hours of administration of previous dose of Infanrix.
- •Thrombocytopenia following a previous dose of M-M-RII or its component vaccines.
- •Inability to contact a parent/guardian of the subject by telephone.
- •Blood dyscrasias (including current thrombocytopenia), leukemia, lymphomas or other malignant neoplasms affecting the bone marrow or lymphatic systems.
- •Family history of congenital or hereditary immunodeficiency, unless the immune competence of the subject was demonstrated.
研究组 & 干预措施
SB213503 lot 1 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 1 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: SB213503 lot 1 (Biological)
SB213503 lot 2 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 2 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: SB213503 lot 2 (Biological)
SB213503 lot 3 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 3 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: SB213503 lot 3 (Biological)
Infanrix + IPOL + M-M-R Group
Subjects aged 4 to 6 years received a dose of Infanrix and a dose of IPOL vaccines separately and a dose of M-M-R II vaccine. Infanrix was administered by deep intramuscular injection in the upper left deltoid. IPOL was administered subcutaneously in the lower right deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: M-M-R II (Biological)
Infanrix + IPOL + M-M-R Group
Subjects aged 4 to 6 years received a dose of Infanrix and a dose of IPOL vaccines separately and a dose of M-M-R II vaccine. Infanrix was administered by deep intramuscular injection in the upper left deltoid. IPOL was administered subcutaneously in the lower right deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: IPOL (Biological)
Infanrix + IPOL + M-M-R Group
Subjects aged 4 to 6 years received a dose of Infanrix and a dose of IPOL vaccines separately and a dose of M-M-R II vaccine. Infanrix was administered by deep intramuscular injection in the upper left deltoid. IPOL was administered subcutaneously in the lower right deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: Infanrix (Biological)
SB213503 lot 3 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 3 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: M-M-R II (Biological)
SB213503 lot 2 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 2 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: M-M-R II (Biological)
SB213503 lot 1 + M-M-R Group
Subjects aged 4 to 6 years received a dose of lot 1 of SB213503 vaccine and a dose of M-M-R II vaccine.
SB213503 was administered by deep intramuscular injection in the left deltoid. M-M-R II was co-administered as a subcutaneous injection in the upper right deltoid.
干预措施: M-M-R II (Biological)
结局指标
主要结局
Geometric Mean Concentrations (GMCs) for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies in a Subset of Subjects
时间窗: At Month 1 (i.e. one month after vaccination)
GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in international units per milliliter (IU/mL).
Number of Subjects With Booster Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects
时间窗: At Month 1 (i.e. one month after vaccination)
Vaccine response defined as: For initially seronegative subjects \[pre-booster antibody concentration below (\<) cut-off of 5 EL.U/mL\] with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥ 20 EL.U/mL). For initially seropositive subjects with pre-booster antibody concentration ≥ 5 EL.U/mL and \< 20 EL.U/mL with an increase of at least 4 times the pre-booster antibody concentration one month after vaccination. For initially seropositive subjects with pre-booster antibody concentration ≥ 20 EL.U/mL with an increase of at least 2 times the pre-booster antibody concentration one month after vaccination.
Geometric Mean Concentrations (GMCs) for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies in a Subset of Subjects
时间窗: At Month 1 (i.e. one month after vaccination)
GMCs were measured by Enzyme-Linked Immunosorbent assay (ELISA), expressed in ELISA units per milliliter (EL.U/mL).
Geometric Mean Titers (GMTs) for Anti-poliovirus Types 1, 2 and 3 Antibodies in a Subset of Subjects
时间窗: At Month 1 (i.e. one month after vaccination)
GMTs were measured by Neutralization assay and expressed in titers.
Number of Subjects With Booster Response Against Diphtheria Toxoid (D) and Tetanus Toxoid (T) Antigens in a Subset of Subjects
时间窗: At Month 1 (i.e. one month after vaccination)
Vaccine response defined as: For initially seronegative subjects \[pre-booster antibody concentration below (\<) cut-off of 0.1 international units per milliliter (IU/mL)\] with an increase of at least four times the cut-off one month after vaccination \[post-booster antibody concentration greater than or equal to (≥) 0.4 IU/mL\]. For initially seropositive subjects (pre-booster antibody concentration ≥ 0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination.
Number of Subjects With Circumferential Swelling at the Injection Site
时间窗: Within 4 days (Day 0-3) after vaccination
Swelling (at the SB213503 \& Infanrix injection sites) was categorized as an increase of \> or ≤ 30 mm in mid upper arm circumference compared to baseline measurement or with an increase in mid upper arm missing; extent of swelling \> or ≤ 50 % of upper arm length, or diameter of injection site missing.
次要结局
- Number of Subjects With Any Unsolicited Adverse Events (AEs)(Within 31 days (Days 0-30) post-vaccination period)
- Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) Antigens in a Subset of Subjects(At Month 1 (i.e. one month after vaccination))
- Number of Seroprotected Subjects Against Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects(At Month 1 (i.e. one month after vaccination))
- Number of Seropositive Subjects Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens in a Subset of Subjects(At Month 1 (i.e. one month after vaccination))
- Number of Subjects With Booster Response for Poliovirus Types 1, 2 and 3 Antigens in a Subset of Subjects(At Month 1 (i.e. one month after vaccination))
- Number of Seroprotected Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects(At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination))
- Number of Subjects With Any and Grade 3 Increase in the Mid-upper Arm Circumference at the Injection Site(During the 4-day (Day 0-3) post-vaccination period)
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms Specific to M-M-R II Vaccination(During the 15-day (Day 0-14) post-vaccination period)
- Number of Subjects With Serious Adverse Events (SAEs)(During the entire study period (from Day 0 through 6 months [minimum 182 days post-vaccination]))
- Number of Subjects With Anti-D and Anti-T Antibody Concentrations Greater Than or Equal to (≥) 1 IU/mL(At Month 1 (i.e. one month after vaccination))
- Geometric Mean Titers (GMTs) for Serum Haemagglutination-inhibition (HI) Anti-H1N1, Anti-H3N2 and Anti-B Antibodies in a Subset of Subjects(At Day 0 (i.e. before vaccination) and at Month 1 (i.e. one month after vaccination))
- Number of Seroconverted Subjects Against Influenza Virus Strains H1N1, H3N2, and B in a Subset of Subjects(At Month 1 (i.e. one month after vaccination))
- Number of Subjects With Onset of Chronic Illness(es) and AE(s) Leading to Emergency Room (ER) or to Physician Office Visits(During the extended safety follow-up phase (i.e. 5 months following the active phase [from Day 31 up to minimum 182 days post-vaccination]))
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 4-day (Day 0-3) post-vaccination period)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 4-day (Day 0-3) post-vaccination period)