A Study to Assess the Immunogenicity and Safety of GSK Biologicals' Infanrix-IPV/Hib Vaccine Administered as a Three-dose Vaccination Course at 3, 4.5 and 6 Months of Age and a Booster Dose at 18 Months of Age in Healthy Infants in Russia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immune response, safety and reactogenicity after receiving combined DTPa-IPV/Hib vaccine when administered as a three-dose primary vaccination course at 3, 4.5 and 6 months of age and as a booster dose at 18 months of age in Russian healthy children according to the Russian immunisation schedule

Official Title
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Immunogenicity and Safety of GSK Biologicals' Combined Diphtheria-tetanus-acellular Pertussis-inactivated Poliovirus and Haemophilus Influenzae Type b (DTPa-IPV/Hib) Conjugate Vaccine

Conditions
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Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus Influenzae Type b

Intervention / Treatment
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* Biological: Infanrix-IPV/Hib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representatives [LARs] who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female child between 3 and 4 months of age at the time of the first vaccination. Written informed consent obtained from the parents/LARs of the subject prior to performing any study specific procedure. Healthy subjects as established by medical history and clinical examination before entering into the study. Born full-term. Exclusion Criteria: Child in care Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting since birth. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Administration of long-acting immune-modifying drugs at any time during the study period Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of hepatitis B and other vaccines given as part of the national immunisation schedule and as part of routine vaccination practice, that are allowed at any time during the study period. Seasonal or pandemic influenza vaccine can be given at any time during the study, and according to the Summary of Product Characteristics and national recommendations. 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 Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Hib diseases. History of diphtheria, tetanus, pertussis, poliomyelitis and Hib diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Family history of congenital or hereditary immunodeficiency. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Major congenital defects. Serious chronic illness. History of any neurological disorders or seizures. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥37.5°C for oral, axillary or tympanic route, or ≥38.0°C for rectal route. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 19 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DTPa-IPV/Hib Group<br>All subjects receive three doses of primary vaccination of the study vaccine, Infanrix-IPV/Hib (DTPa-IPV/Hib), at 3, 4.5 and 6 months of age and a single dose of booster vaccination at 18 months of age. The vaccine is administered intramuscularly into the upper side of the thigh on the right/left side. | Biological: Infanrix-IPV/Hib<br>* Subjects receive Infanrix-IPV/Hib three-dose primary vaccination course at 3, 4.5 and 6 months of age and a booster dose at 18 months of age. The vaccine is administered intramuscularly into the upper side of the thigh on the right/left side.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T), Post Primary Vaccination | A seroprotected subject is a subject whose anti-D and anti-T antibody concentration was greater than or equal to (≥) 0.1 International Units per milliliter (IU/mL). | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3, Post Primary Vaccination | A seroprotected subject is a subject whose anti-poliovirus types 1, 2 and 3 antibody titer was ≥ 8 ED50. | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Number of Seroprotected Subjects for Anti-polyribosyl Ribitol Phosphate (Anti-PRP), Post Primary Vaccination | A seroprotected subject is a subject whose anti-PRP antibody concentration was ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Number of Seropositive Subjects for Anti-pertussis (Anti- PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN), Post Primary Vaccination | A seropositive subject is a subject whose antibody concentration was ≥ 2.046 IU/mL for anti-FHA, ≥ 2.187 IU/mL for anti-PRN and ≥ 2.693 IU/mL for anti-PT. | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-D and Anti-T, Post Booster Vaccination | A seroprotected subject is a subject whose anti-D and anti-T antibody concentration was ≥ 0.1 IU/mL. | At Month 16 (i.e. one month after booster vaccination) | 
| Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3, Post Booster Vaccination | A seroprotected subject is a subject whose anti-poliovirus types 1, 2 and 3 antibody titer was ≥ 8 ED50. | At Month 16 (i.e. one month after booster vaccination) | 
| Number of Seroprotected Subjects for Anti-PRP, Post Booster Vaccination | A seroprotected subject is a subject whose anti-PRP antibody concentration was ≥ 0.15 µg/mL. | At Month 16 (i.e. one month after booster vaccination) | 
| Number of Seropositive Subjects for Anti- PT, Anti-FHA and Anti-PRN, Post Booster Vaccination | A seropositive subject is a subject whose antibody concentration was ≥ 2.046 IU/mL for anti-FHA, ≥ 2.187 IU/mL for anti-PRN and ≥ 2.693 IU/mL for anti-PT. | At Month 16 (i.e. one month after booster vaccination) | 
| Antibody Concentrations for Anti-D and Anti-T, Post Primary Vaccination | The antibody concentrations for anti-D and anti-T were presented as geometric mean concentrations (GMCs) and expressed as IU/mL. | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Antibody Concentrations for Anti-D and Anti-T, Post Booster Vaccination | The antibody concentrations for anti-D and anti-T were presented as geometric mean concentrations (GMCs) and expressed as IU/mL. | At Month 16 (i.e. one month after booster vaccination) | 
| Antibody Titers for Anti-polio Types 1, 2 and 3, Post Primary Vaccination | The antibody titers for anti-polio types 1, 2 and 3 were presented as geometric mean titres (GMTs). | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Antibody Titers for Anti-polio Types 1, 2 and 3, Post Booster Vaccination | The antibody titers for anti-polio types 1, 2 and 3 were presented as geometric mean titres (GMTs). | At Month 16 (i.e. one month after booster vaccination) | 
| Antibody Concentration for Anti-PRP, Post Primary Vaccination | The antibody concentrations for anti-PRP were presented as geometric mean concentrations (GMCs) and expressed as µg/mL. | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Antibody Concentration for Anti-PRP, Post Booster Vaccination | The antibody concentrations for anti-PRP were presented as geometric mean concentrations (GMCs) and expressed as µg/mL. | At Month 16 (i.e. one month after booster vaccination) | 
| Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN, Post Primary Vaccination | The antibody concentrations for anti-PT, anti-FHA and anti-PRN were presented as GMCs and expressed as IU/mL. | At Month 4 (i.e. one month after 3rd dose of primary vaccination) | 
| Antibody Concentrations for Anti-PT, Anti-FHA and Anti-PRN, Post Booster Vaccination | The antibody concentrations for anti-PT, anti-FHA and anti-PRN were presented as GMCs and expressed as IU/mL. | At Month 16 (i.e. one month after booster vaccination) | 
| Number of Subjects With Any Solicited Local Adverse Events (AEs) Following Each Dose of Primary Vaccination | The solicited local AEs assessed were pain, redness and swelling at injection site. Any = Occurrence of the AE regardless of the intensity grade. | During the 4-day (Days 0-3) follow-up period after each primary vaccination dose (i.e. at Day 0, at Month 1.5 and at Month 3) | 
| Number of Subjects With Any Solicited Local AEs Following Booster Vaccination | The solicited local AEs assessed were pain, redness and swelling at injection site. Any = Occurrence of the AE regardless of the intensity grade. | During the 4-day (Days 0-3) follow-up period after booster vaccination dose (i.e. at Month 15) | 
| Number of Subjects With Any Solicited General AEs Following Each Dose of Primary Vaccination | The solicited general AEs assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any = Occurrence of the AE regardless of the intensity grade. Any fever = Fever (axillary) ≥ 37.5°C. | During the 4-day (Days 0-3) follow-up period after each primary vaccination dose (i.e. at Day 0, at Month 1.5 and at Month 3) | 
| Number of Subjects With Any Solicited General AEs Following Booster Vaccination | The solicited general AEs assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any = Occurrence of the AE regardless of the intensity grade. Any fever = Fever (axillary) ≥ 37.5°C. | During the 4-day (Days 0-3) follow-up period after booster vaccination dose (i.e. at Month 15) | 
| Number of Subjects With Unsolicited AEs Following Each Dose of Primary Vaccination | An unsolicited AE was defined as any AE reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of the intensity grade. | During the 31-day (Days 0-30) follow-up period after each primary vaccination dose (i.e. at Day 0, at Month 1.5 and at Month 3) | 
| Number of Subjects With Unsolicited AEs Following Booster Vaccination | An unsolicited AE was defined as any AE reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = Occurrence of the AE regardless of the intensity grade. | During the 31-day (Days 0-30) follow-up period after booster vaccination dose (i.e. at Month 15) | 
| Number of Subjects With Serious Adverse Events (SAEs) | The SAEs assessed included any untoward medical occurrences that resulted in death, were life threatening, required hospitalisation or prolongation of existing hospitalisation or resulted in disability/incapacity. Any = Occurrence of the AE regardless of the intensity grade. | During the entire study period (i.e. from Day 0 until Month 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary dose, Reactogenicity, Immunogenicity, Booster dose, Combined vaccine, Russian Infants, Infanrix®-IPV/Hib