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

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.

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)

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Infanrix hexa; Biological: Pneumococcal conjugate vaccine GSK1024850A

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 115 27
    • GSK Investigational Site
  • Athens, Greece, 11527
    • GSK Investigational Site
  • Ioannina, Greece, 452 21
    • GSK Investigational Site
  • Rio/Patras, Greece, 26500
    • GSK Investigational Site
  • Thessaloniki, Greece, 54636
    • GSK Investigational Site
• Spain
  • Burgos, Spain, 09005
    • GSK Investigational Site
  • Madrid, Spain, 28047
    • GSK Investigational Site
  • Móstoles/Madrid, Spain, 28935
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Omenaca F, Merino JM, Tejedor JC, Constantopoulos A, Papaevangelou V, Kafetzis D, Tsirka A, Athanassiadou F, Anagnostakou M, Francois N, Borys D, Schuerman L. Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine. Pediatrics. 2011 Aug;128(2):e290-8. doi: 10.1542/peds.2010-1184. Epub 2011 Jul 4.
• Omeneca F et al. Vaccination of pre-term infants with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHID-CV). Abstract presented at the 27th annual ESPID meeting, Brussels, Belgium, 9-13 June 2009.
• Omeneca F et al. Immunogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) following primary and booster vaccination in preterm-born children. Abstract presented at Excellence In Paediatrics. Florence, Italy, 3-6 December 2009.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2006
• Primary Completion (Actual): July 2, 2007
• Study Completion (Actual): May 2, 2008

Study Registration Dates

• First Submitted: October 20, 2006
• First Submitted That Met QC Criteria: October 20, 2006
• First Posted (Estimate): October 23, 2006

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Preterm; Pneumococcal disease
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 107737

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: 107737
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register