Clinical trial NCT00390910: Study to Evaluate the Safety and Immunogenicity of a 10-valent Pneumococcal Conjugate Vaccine in Preterm Infants
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Pneumococcal vaccine
Preterm
Safety
Pneumococcal disease
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-10-23
Enrollment: 286
Sex: ALL
Minimum age (years): 8
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off
timeFrame: 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 outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: 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)
measure: Number of Subjects With Any and Grade 3 Solicited General Symptoms
timeFrame: 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)
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: 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)
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: Throughout the active phase of the study (from the first vaccine administration (Month 0) up to 1 month after the third vaccine administration (Month5).
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: 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).
measure: 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
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: 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
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Concentrations of Antibodies Against Protein D (Anti-PD)
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-diphtheria (Anti DT) and Anti-tetanus Toxoids (Anti TT) Antibody Concentrations ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Antibody Concentrations for Anti-diphtheria and Tetanus Toxoids ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations ≥ th Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Antibody Concentration for Anti-pertussis Toxoid (Anti-PT) , Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations ≥ the Cut-off.
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titres
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Antibody Titers for Polio Type 1, 2 and 3 ≥ the Cut-off
timeFrame: One month after the 3rd vaccine dose (Month 5)
measure: Number of Subjects With Vaccine Response to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN)
timeFrame: One month after the 3rd vaccine dose (Month 5)
Other outcomes:
Locations:
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Ioannina
country: Greece
facility: GSK Investigational Site
city: Rio/Patras
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Móstoles/Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.