A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of GSK's combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib) versus MCM Vaccine BV's DTaP5-HBV-IPV-Hib vaccine administered to healthy infants and toddlers, between 6 and 12 weeks of age at the time of first vaccination, based on a 2-, 4-, and 12-months of age vaccination schedule.

Official Title
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A Phase IV, Single-blind, Randomised, Controlled, Multi-country Study to Evaluate the Immunogenicity and Safety of GSK's Infanrix Hexa (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis (DTaP5-HBV-IPV Hib), When Administered Intramuscularly According to a 2-, 4- and 12-month Schedule in Healthy Infants and Toddlers

Conditions
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Diphtheria

Intervention / Treatment
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* Biological: DTPa-HBV-IPV/Hib
* Biological: DTaP5-HBV-IPV-Hib
* Biological: Pneumococcal 13-valent conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative(s) (LAR[s]) who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., return for follow-up visits). Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. A male or female child between and including 6 and 12 weeks of age (42 to 84 days) at the time of the first vaccination. Subject born after at least 37 weeks of gestation. Healthy subjects as established by the investigator based on medical history and the clinical examination before entering into the study. Exclusion Criteria: Any clinical condition that, in the opinion of the investigator, might pose any risk to the subject due to participation in the study. As with other vaccines, administration of DTPa-HBV-IPV/Hib should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contraindication. Known history of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hib diseases since birth. History of any reaction or hypersensitivity likely to be caused or exacerbated by any excipient or active component of the vaccine(s). Any confirmed or suspected immunosuppressive or immunodeficient condition, including malignancies, based on medical history and physical examination (no laboratory testing required). Family history of congenital or hereditary immunodeficiency. Major congenital defects, as assessed by the investigator. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined via medical history including physical examination. Medical history of neurological disorder, including seizures. Previous vaccination for diphtheria, tetanus, pertussis, HBV, poliomyelitis, Hib diseases and previous vaccination against pneumococcal infection with pneumococcal conjugate vaccine, with the exception of a birth dose of HBV vaccine, which may be given in accordance with local recommendations. Use of any investigational or nonregistered product (drug, vaccine, or medical device) other than the study vaccine(s) during the period starting 30 days before the first dose of study vaccine(s) (Day -29 to Day 1), or planned use 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(s) with the exception of administration of vaccines given as part of the national immunization schedule and as part of routine vaccination practice, e.g., rotavirus vaccine, that are allowed at any time during the study period. In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization programme, the time period described above can be reduced if necessary for that mass vaccination vaccine, provided this vaccine/product(s) is licensed and used according to its Product Information. Administration of long-acting immune-modifying drugs in the period starting 30 days before the first dose and at any time during the study period. Administration of immunoglobulins and/or any blood products or plasma derivatives from birth or planned administration during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day (for paediatric subjects), or equivalent. Inhaled and topical steroids are allowed. 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 (drug or medical device). Child in care.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DTPa-HBV-IPV/Hib Investigational Group<br>All subjects in this group receive 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13-valent conjugate vaccine at 2, 4, and 12 months of age. | Biological: DTPa-HBV-IPV/Hib<br>* 3 doses (1 each at 2, 4 and 12 months of age) of DTPa-HBV-IPV/Hib vaccine administered by intramuscular injection into the right thigh<br>* Other names: Infanrix hexa;Biological: Pneumococcal 13-valent conjugate vaccine<br>* 3 doses (1 each at 2, 4 and 12 months of age) of pneumococcal 13-valent conjugate vaccine administered by intramuscular injection into the left thigh<br>* Other names: Prevenar 13;|
| Active Comparator: DTaP5-HBV-IPV-Hib Comparator Group<br>All subjects in this group receive 3 doses (2 primary doses and 1 booster dose) of DTaP5-HBV-IPV-Hib vaccine co-administered with 3 doses of pneumococcal 13-valent conjugate vaccine at 2, 4, and 12 months of age. | Biological: DTaP5-HBV-IPV-Hib<br>* 3 doses (1 each at 2, 4 and 12 months of age) of DTaP5-HBV-IPV-Hib vaccine administered by intramuscular injection into the right thigh<br>* Other names: Vaxelis;Biological: Pneumococcal 13-valent conjugate vaccine<br>* 3 doses (1 each at 2, 4 and 12 months of age) of pneumococcal 13-valent conjugate vaccine administered by intramuscular injection into the left thigh<br>* Other names: Prevenar 13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-PRP antibody concentrations at Month 11, based on Per protocol set (PPS) | Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs) and expressed in microgram per milliliter (μg/mL), as assessed by Enzyme-linked immunosorbent assay (ELISA). | At Month 11 (i.e., 1 month post-booster vaccination) | 
| Percentage of subjects with anti-PRP antibody concentrations equal to or above (≥) 5 µg/mL at Month 11, based on PPS | The percentage of subjects with anti-PRP antibody concentrations ≥ 5 µg/mL (as assessed by ELISA) is reported. | At Month 11 (i.e., 1 month post-booster vaccination) | 
| Anti-PRP antibody concentrations at Month 11, based on the Exposed Set (ES) | Anti-PRP antibody concentrations are presented as GMCs and expressed in μg/mL, as assessed by ELISA. | At Month 11 (i.e., 1 month post-booster vaccination) | 
| Percentage of subjects with anti-PRP antibody concentrations ≥ 5 µg/mL at Month 11, based on ES | The percentage of subjects with anti-PRP antibody concentrations ≥ 5 µg/mL (as assessed by ELISA) is reported. | At Month 11 (i.e., 1 month post-booster vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with anti-PRP antibody concentrations ≥ 0.15 µg/mL | The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold (i.e., 0.15 µg/mL) for protection is reported. | At Month 3 (i.e., 1 month post-primary vaccination), Month 10 (i.e., pre-booster), Month 11 (i.e., 1 month post-booster vaccination) | 
| Percentage of subjects with anti-PRP antibody concentrations ≥ 1.0 µg/mL | The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for long-term protection is reported. The threshold for long-term protection is 1.0 µg/mL. | At Month 3 (i.e., 1 month post-primary vaccination), Month 10 (i.e., pre-booster), Month 11 (i.e., 1 month post-booster vaccination) | 
| Anti-PRP antibody concentrations | Anti-PRP antibody concentrations are presented as GMCs and expressed in μg/mL, as assessed by ELISA. | At Month 3 (i.e., 1 month post-primary vaccination), Month 10 (i.e., pre-booster), Month 11, (i.e., 1 month post-booster vaccination) | 
| Number of subjects with unsolicited adverse events (AEs) | An AE is any untoward medical occurrence in a subject or subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | During the 31-day (Days 1-31) follow-up period after each vaccination | 
| Number of subjects with serious adverse events (SAEs) | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect. | During the entire study period (Day 1 - Month 11) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Inactivated poliovirus, Haemophilus influenzae type b, Primary immunization, Immunogenicity, Safety, Diphtheria, Tetanus, Acellular pertussis