A Study to Compare the Immunogenicity of GSK Biologicals' 10Pn-PD-DiT 4-dose Presentation to the Licensed 1-dose Synflorix™ (10Pn-PD-DiT) Vaccine When Co-administered With DTPw-combination Vaccine in Healthy Infants

Study Overview
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Brief Summary
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The primary aim of the study is to demonstrate that an investigational 4-dose presentation of the 10Pn-PD-DiT vaccine with preservative is non-inferior to the licensed presentation of Synflorix (preservative-free) in terms of immune responses to the 10 vaccine pneumococcal serotypes (primary objective) and to the vaccine-related pneumococcal serotype 19A (first secondary objective), after administration of a 3-dose primary vaccination course at 6, 10 and 18 weeks of age co-administered with the first 2 doses of DTPw-HBV/Hib vaccine given at 6, 10 and 14 weeks of age (according to the Expanded Program on Immunization (EPI) schedule). In addition, the study will also assess the safety, reactogenicity, immunogenicity and antibody persistence (approximately 7 months following primary vaccination) of the 4-dose presentation of the 10Pn-PD-DiT vaccine given as primary vaccination schedule at 6, 10 and 18 weeks of age followed by a booster dose at 38 weeks. This study also aims at assessing the safety, reactogenicity and immunogenicity of the 4-dose presentation of the 10Pn-PD-DiT vaccine when given as a booster dose at approximately 9 months of age.

Official Title
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Study to Compare Immunogenicity of GSK Biologicals' 10Pn-PD-DiT 4-dose Presentation to the Licensed Synflorix™ (10Pn-PD-DiT) Vaccine When Co-administered With DTPw-combination Vaccine in Healthy Infants

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (4-dose presentation)
* Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (1-dose presentation)
* Biological: DTPw-HBV/Hib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects for whom, in the opinion of the investigator, the parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol (e.g., return for vaccination and follow-up visits). A male or female between, and including 6-10 weeks (42-76 days) of age at the time of the first vaccination. Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the subject. For all subjects, the consent form should be countersigned by a witness. Healthy subjects as established by medical history and clinical examination before entering into the study. Born full-term (i.e., after a gestation period from 37 to 42 weeks). Exclusion Criteria: Child in care. 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 in total) of immunosuppressants or other immune-modifying drugs since birth. Inhaled and topical steroids are allowed. Planned administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab). Administration or planned administration of a vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of study vaccines and ending 30 days after with the following exceptions: 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, H. influenzae type b and/or S. pneumoniae. History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, and H. influenzae type b disease. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Family history of congenital or hereditary immunodeficiency. Major congenital defects or 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 on rectal route. The preferred route for recording temperature in this study will be axillary. 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 (Hepatitis B immunoglobulins at birth are allowed). Any medical condition which might interfere with the assessment of the study objectives in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 76 Days

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10Pn_4d Group<br>Subjects received 10Pn-PD-DIT, in its investigational 4-dose presentation (4 doses in total with each single dose injected at Study Months 0, 1, 3 and 8), co administered with DTPw-HBV/Hib vaccine (3 doses injected at Study Months 0, 1 and 2). | Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (4-dose presentation)<br>* 4 doses by intramuscular injection in the right left anterolateral thigh<br>* Other names: GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate GSK1024850A (10Pn-PD-DiT);Biological: DTPw-HBV/Hib<br>* 3 doses by intramuscular injection in the left anterolateral thigh<br>* Other names: GSK Biologicals' diphtheria-tetanus-whole cell pertussis-hepatitis B and Haemophilus influenzae type b vaccine;|
| Active Comparator: 10Pn Group<br>Subjects received 10Pn-PD-DIT, in its licensed 1-dose presentation (4 doses in total with each single dose injected at Study Months 0, 1, 3 and 8), co administered with DTPw-HBV/Hib vaccine (3 doses injected at Study Months 0, 1 and 2). | Biological: Pneumococcal vaccine GSK1024850A (10Pn-PD-DiT) vaccine (1-dose presentation)<br>* 4 doses by intramuscular injection in the right anterolateral thigh<br>* Other names: GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate GSK1024850A (10Pn-PD-DiT) vaccine;Biological: DTPw-HBV/Hib<br>* 3 doses by intramuscular injection in the left anterolateral thigh<br>* Other names: GSK Biologicals' diphtheria-tetanus-whole cell pertussis-hepatitis B and Haemophilus influenzae type b vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Serotypes (Epoch 001) | Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. Primary outcome results correspond to antibody concentrations for the 10 vaccine serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Serotypes (Epoch 002) | Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. | At Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 001) | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, 19 A ,-19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. | At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes (Epoch 002) | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. | At study Month 8 and Month 9, e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 001) | Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (≥) 153 EL.U/mL. | At study Month 4, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Concentrations of Antibodies Against Protein D (Anti-PD) (Epoch 002) | Anti-PD antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The cut-off of the assay was an anti-PD antibody concentration higher than or equal to (≥) 153 EL.U/mL. | At study Month 9, e.g.: at one month post booster vaccination with pneumococcal vaccine | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms (Epoch 001) | Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm). Dose 1 = 10Pn-PD-DIT+DTPw-HBV/Hib at 6 weeks of age. Dose 2 = 10Pn-PD-DIT+DTPw-HBV/Hib at 10 weeks of age. Dose 4 = 10Pn-PD-DIT at 18 weeks of age. | Within the 4-day (Days 0-3) post-vaccination period following each primary dose of 10Pn-PD-DiTvaccine | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms (Epoch 002) | Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm). | Within the 4-day (Days 0-3) period after booster vaccination | 
| Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination(Epoch 001) | Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness, Loss of appetite and Fever (axillary route - temperature equal or higher than [≥] 37.5 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability/Fussiness = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = (axillary) temperature higher than (>) 39.5°C. Related = Occurrence of the specified symptom assessed by the investigator as causally related to vaccination. Dose 1 = 10Pn-PD-DIT+DTPw-HBV/Hib at 6 weeks of age. Dose 2 = 10Pn-PD-DIT+DTPw-HBV/Hib at 10 weeks of age. Dose 4 = 10Pn-PD-DIT at 18 weeks of age. | Within the 4-day (Days 0-3) post-vaccination period following each primary dose of 10Pn-PD-DiTvaccine | 
| Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination (Epoch 002) | Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness, Loss of appetite and Fever (axillary route - temperature equal or higher than [≥] 37.5 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability/Fussiness = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = (Axillary) temperature higher than (>) 39.5°C. | Within the 4-day (Days 0-3) period after booster vaccination | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) (Epoch 001) | An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. | Within the 31-day (Days 0-30) period post primary vaccination, across doses | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) (Epoch 002) | An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. | Within the 31-day (Days 0-30) period post booster vaccination | 
| Number of Subjects With Any Serious Adverse Events (SAEs) (Epoch 001) | An SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of an SAE, regardless of relationship to vaccination. | From Month 0 to Month 4 | 
| Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study | An SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalization, as per the medical or scientific judgement of the physician. Any = Occurrence of an SAE, regardless of relationship to vaccination. | From Day 0 to Month 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Invasive disease by Streptococcus pneumoniae (S. pneumoniae) (including sepsis, meningitis, pneumonia, bacteraemia and acute otitis media), Infants, Multidose, Haemophilus influenzae, Streptococcus pneumoniae, Preservative, Safety, Pneumonia, Immunogenicity, Pneumococcal conjugate vaccine, Acute otitis media caused by non-typeable Haemophilus influenzae (NTHi)., Respiratory tract infections