Immunogenicity and Safety of Two Formulations of GSK Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants

Study Overview
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Brief Summary
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The purpose of this study is to assess the immunogenicity, reactogenicity and safety of two formulations of GSK Biologicals' pneumococcal vaccine (2830929A and 2830930A) administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Detailed Description
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The purpose of this study is to assess the immunogenicity of the two formulations of GSK Biologicals' pneumococcal vaccine 2830929A (11-valent vaccine or 11Pn vaccine) and 2830930A (12-valent vaccine or 12Pn vaccine), when administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life, when compared to immune responses to the licensed vaccines Synflorix™ and Prevnar 13™, and to assess the reactogenicity and safety of these two same investigational formulations when administered according to this schedule. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa™) vaccine will be co-administered in infants with the pneumococcal study vaccines.

Official Title
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Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal conjugate vaccine GSK2830929A
* Biological: Pneumococcal conjugate vaccine GSK2830930A
* Biological: Synflorix™
* Biological: Prevnar 13™
* Biological: Infanrix hexa™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LARs) can and will comply with the requirements of the protocol. A male or female between, and including 6 to 12 weeks (42-90 days) of age at the time of the first vaccination. In addition, the first pneumococcal and DTPa-HBV-IPV/Hib vaccination should be given in accordance with the official national recommendations for the immunisation schedule of infants. Written informed consent obtained from the parents/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Born after a gestation period of at least 36 weeks. Exclusion Criteria: Child in care. Use of any investigational or non-registered product 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 of immunosuppressants or other immune-modifying drugs since birth. Planned administration/administration of a vaccine containing diphtheria toxoid, tetanus toxoid (except MenC-TT in Spain) or CRM197 and not foreseen by the study protocol during any time of the study period, or of any other vaccines not foreseen by the protocol in the period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the following exceptions: Licensed influenza vaccines are always allowed, even if concomitantly administered with the study vaccines. Licensed rotavirus vaccines are allowed if administered at least 7 days before or after each dose of study of vaccines. Licensed MenC-TT vaccine is allowed in Spain and should be concomitantly administered with the study vaccine at around 2, 4 and 12-15 months of age. In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by the public health authorities, outside the routine immunization program, that vaccine can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental 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 product . 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(s). Major congenital defects or serious chronic illness, including Kawasaki's syndrome. History of any neurological disorders or seizures, including conditions such as hypotensive-hyporesponsive episodes, encephalopathy and any convulsions (afebrile and febrile). Acute disease and/or fever at the time of enrolment. Administration of immunoglobulins and/or any blood products since birth or planned administration during study period. Previous vaccination against diphtheria, tetanus, pertussis, polio, H. influenzae type b. Previous vaccination against S. pneumoniae. History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, H. influenzae type b disease. 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: 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 11Pn Group<br>Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate). | Biological: Pneumococcal conjugate vaccine GSK2830929A<br>* Intramuscular injection<br>Biological: Infanrix hexa™<br>* Intramuscular injection<br>|
| Experimental: 12Pn Group<br>Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate). | Biological: Pneumococcal conjugate vaccine GSK2830930A<br>* Intramuscular injection<br>Biological: Infanrix hexa™<br>* Intramuscular injection<br>|
| Active Comparator: Synflorix Group<br>Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate). | Biological: Synflorix™<br>* Intramuscular injection<br>Biological: Infanrix hexa™<br>* Intramuscular injection<br>|
| Active Comparator: Prevnar13 Group<br>Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate ). | Biological: Prevnar 13™<br>* Intramuscular injection<br>Biological: Infanrix hexa™<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Serotypes During the Primary Phase of the Study | Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -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 all serotypes presented at the exception of those for the antibodies against the cross-reactive pneumococcal serotype 3 (ANTI-3). | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Percentage (%) of Subjects (Synflorix and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes | N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA). | 1 month post-dose 3 (primary phase) | 
| Percentage (%) of Subjects (Prevnar13 and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-19A Pneumococcal Serotype | N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 19A (ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA). | 1 month post-dose 3 (primary phase) | 
| Percentage (%) of Subjects (Synflorix and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes | N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA). | 1 month post-dose 3 (primary phase) | 
| Percentage (%) of Subjects (Prevnar13 and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-6A and 19A Pneumococcal Serotypes | N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 6A and 19A (ANTI-6A and 19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA). | 1 month post-dose 3 (primary phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Serotypes During the Booster Phase of the Study | Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -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. Analysis of concentrations of antibodies against the cross-reactive pneumococcal serotype 6C (ANTI-6C) will not be performed due to unavailability of a specific qualified assay. | At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Primary Phase of the Study | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. Testing for opsonophagocytic activity against the cross-reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay. | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Booster Phase of the Study | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19F and -23F). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8. Testing for opsonophagocytic activity against the cross-reactive pneumococcal serotype 6C will not be performed due to unavailability of a specific qualified assay. | At study Month 11, e.g.: at one month post booster vaccination with pneumococcal vaccine | 
| Concentrations of Antibodies Against Protein D (Anti-PD) During the Primary Phase of the Study | 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 (≥) 100 EL.U/mL. | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Concentrations of Antibodies Against Protein D (Anti-PD) During the Booster Phase of the Study | 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 (≥) 100 EL.U/mL. | At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Phase | 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) post-vaccination period following each primary dose (D). | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Phase of the Study | 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, During the Primary Phase of the Study | Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [≥] 38.0 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 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C. | Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D). | 
| Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Booster Phase of the Study | Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness (Irr./Fuss.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [≥] 38.0 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 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C. | Within the 4-day (Days 0-3) period after booster vaccination | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Primary Phase of the Study | 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) During the Booster Phase of the Study | 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)During the Primary Phase of the Study | A 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 hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination. | From Month 0 to Month 3 | 
| Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study | A 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 hospitalisation, as per the medical or scientific judgement of the the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination. | From Day 0 to Month 11 | 
| Antibody Concentrations Against Pneumococcal Serotype 6A During the Booster Phase of the Study | Antibodies assessed for this outcome measure was that against the cross-reactive pneumococcal serotype 6A (ANTI-6A). 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 study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Primary Phase of the Study | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) serotype-specific Lower Limit of Quantification (143). | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Booster Phase of the Study | Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 19A (OPA-19A). The cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) serotype-specific Lower Limit of Quantification (143). | At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine | 
| Antibody Concentrations Against Pneumococcal Serotype 6C During the Primary Phase of the Study. | No analysis was performed on Enzyme-Linked ImmunoSorbent Assay (ELISA) testing for antibody concentrations against vaccine serotype 6C as no specific qualified/validated assay was available. | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Antibody Concentrations Against Pneumococcal Serotype 6C During the Booster Phase of the Study. | No analysis was performed on Enzyme-Linked ImmunoSorbent Assay (ELISA) testing for antibody concentrations against vaccine serotype 6C as no specific qualified/validated assay was available. | At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Primary Phase of the Study | No analysis was performed on opsonophagocytic activity for antibody titers against vaccine serotype 6C as no specific qualified/validated assay was available. | At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine | 
| Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Booster Phase of the Study | No analysis was performed on opsonophagocytic activity for antibody titers against vaccine serotype 6C as no specific qualified/validated assay was available. | At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Streptococcus pneumoniae, Haemophilus influenzae, Pneumococcal vaccine, Infants, Safety, Immunogenicity