Study to Evaluate the Safety and Immunogenicity of a 10-valent Pneumococcal Conjugate Vaccine in Preterm Infants

Study Overview
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Brief Summary
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This study aims to evaluate the safety, reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals´ 10-valent pneumococcal conjugate vaccine when co-administered with diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated polio virus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine in preterm infants as a 3-dose primary immunization course during the first 6 months of life. This protocol posting deals with objectives & outcome measures of the primary study. The objectives & outcome measures of the Booster study are presented in a separate protocol posting (NCT number = 00609492)

Detailed Description
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The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Study to Assess the Safety and Immunogenicity of GSK Biologicals 10-valent Pneumococcal Conjugate Vaccine When Co-administered With DTPa-HBV-IPV/Hib (Infanrix-Hexa) Vaccine in Preterm Infants as a 3-dose Primary Immunization Course During the First 6 Months of Life.

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal conjugate vaccine GSK1024850A
* Biological: Infanrix hexa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol A male or female between, and including, 8-16 weeks (56-118 days) of age at the time of the first vaccination. Written informed consent obtained from the parent or guardian of the subject. Born after a gestation period of >27 weeks (at least 189 days). If full term born, healthy subjects as established by medical history and clinical examination before entering into the study If premature, medically stable condition (not requiring significant medical support or ongoing management for debilitating disease and having demonstrated a clinical course of sustained recovery). Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccines, or planned use during the study period Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs from birth to the first vaccine dose. Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting from one month before the first dose of vaccines and up to Visit 6. Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, Neisseria meningitidis and/or Streptococcus pneumoniae with the exception of vaccines where the first dose can be given within the first two weeks of life according to the national recommendations History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease, Neisseria meningitidis. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurologic disorders or seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past). Acute disease at the time of enrolment. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. Administration of immunoglobulins, with the exception of monoclonal antibodies against RSV, and/or any blood products within one month preceding the first dose of study vaccines or planned administration during the active phase of the study.

Ages Eligible for Study
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Minimum Age: 8 Weeks
Maximum Age: 16 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix™ + Infanrix™ hexa Group I<br>Very preterm infants born after a gestation period of 27-30 weeks (189-216 days) | Biological: Pneumococcal conjugate vaccine GSK1024850A<br>* Intramuscular injection, 3 doses<br>Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses<br>* Other names: DTPa-HBV-IPV/Hib;|
| Experimental: Synflorix™ + Infanrix™ hexa Group II<br>Mild pretem infants born after a gestation period of 31-36 weeks (217-258 days) | Biological: Pneumococcal conjugate vaccine GSK1024850A<br>* Intramuscular injection, 3 doses<br>Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses<br>* Other names: DTPa-HBV-IPV/Hib;|
| Experimental: Synflorix™ + Infanrix™ hexa Group III<br>Infants born after a gestation period of more than 36 weeks (more than 258 days) | Biological: Pneumococcal conjugate vaccine GSK1024850A<br>* Intramuscular injection, 3 doses<br>Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses<br>* Other names: DTPa-HBV-IPV/Hib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off | Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed post doses 1, 2 and 3 of Synflorix or Infanrix hexa vaccine. | Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed included pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (>) 30 millimeters (mm). Any was defined as incidence of the specified symptom regardless of intensity. | Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4) | 
| Number of Subjects With Any and Grade 3 Solicited General Symptoms | Solicited general symptoms assessed included drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all. Any was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. | Within 4 days (Days 0-3) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4) | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An AE is 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. Any was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | Within 31 days (Days 0-30) after each vaccine dose, administered according to a 3-dose schedule at 2-4-6 months of age (Month 0-2-4) | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. | Throughout the active phase of the study (from the first vaccine administration (Month 0) up to 1 month after the third vaccine administration (Month5). | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed included medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity. | Throughout the entire study period starting from the first vaccine dose administration (Month 0) up to the end of the 6-month safety follow-up (ESFU- Month 10). | 
| Number of Subjects With Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Greater Than or Equal to (≥) the Cut-off | The cut-off for the assay was ≥ 0.20 microgram per mililiter (μg/ mL). | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ the Cut-off | The cut-off for the assay was ≥ 0.05 microgram per mililiter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ the Cut-off | The cut-off for the assay was ≥ 8 | One month after the 3rd vaccine dose (Month 5) | 
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8. | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off | The cut-off for the assay was ≥ 0.05 microgram per milliliter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Seropositivity status was defined as anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off | The cut-off for the assay was ≥ 8. | One month after the 3rd vaccine dose (Month 5) | 
| Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Seropositivity status was defined as opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8. | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) ≥ the Cut-off | The cut-off for the assay was ≥ 100 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Concentrations of Antibodies Against Protein D (Anti-PD) | Seropositivity status was defined as anti-PD antibody concentrations ≥ 100 ELISA units per milliliter ( EL.U/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-diphtheria (Anti DT) and Anti-tetanus Toxoids (Anti TT) Antibody Concentrations ≥ the Cut-off | The cut-off for the assay was ≥ 0.1 international units per milliliter (IU/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Antibody Concentrations for Anti-diphtheria and Tetanus Toxoids ≥ the Cut-off | Seroprotection status was defined as anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 IU/mL | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off | The cut-off for the assay was ≥ 0.15 microgram per milliliter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off | The cut-off for the assay was ≥ 1.0 microgram per milliliter (μg/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations ≥ th Cut-off | Seroprotection status was defined as anti-PRP antibody concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations ≥ the Cut-off | The cut-off for the assay was ≥ 5 ELISA unit per milliliter (EL.U/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Antibody Concentration for Anti-pertussis Toxoid (Anti-PT) , Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) | Seropositivity status was defined as anti-PT, anti-FHA, anti-PRN antibody concentrations ≥ 5 EL.U/mL. | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations ≥ the Cut-off. | The cut-off for the assay was ≥ 10 milli-international units per milliliter (mIU/mL). | One month after the 3rd vaccine dose (Month 5) | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | Seroprotection status was defined as Anti-HBs antibody concentrations ≥ 10 mIU/mL | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titres | The cut-off for the assay was ≥ 8. | One month after the 3rd vaccine dose (Month 5) | 
| Antibody Titers for Polio Type 1, 2 and 3 ≥ the Cut-off | Seroprotection status was defined as Anti-polio type 1, Anti-polio type 2 and Anti-polio type 3 antibody titers ≥ 8. | One month after the 3rd vaccine dose (Month 5) | 
| Number of Subjects With Vaccine Response to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) | Vaccine response to PT, FHA and PRN was defined as appearance of antibodies in subjects who are initially seronegative (S-), or at least maintenance of pre-vaccination antibody concentrations in those who are initially seropositive (S+). For the SYNFLORIX™ + INFANRIX™ HEXA GROUP I, no subjects presented initial seropositivity for PT and PRN antigens. | One month after the 3rd vaccine dose (Month 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal vaccine, Preterm, Safety, Pneumococcal disease, Immunogenicity