Clinical trial NCT00586612: Primary & Booster Study to Evaluate the Immunogenicity and Safety of Menitorix Vaccine in Preterm Infants
Official title: Immunogenicity & Safety Study in Preterm & Full-term Infants of GSK Biologicals' Hib-MenC Vaccine, Menitorix™ Co-administered With Infanrix™ Penta & Prevenar™ at 2, 4, 6 Months & as a Booster With Infanrix™ IPV & Prevenar™ at 16-18 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Haemophilus Influenzae Type b
Neisseria Meningitidis
Keywords: Conjugate vaccine
Persistence
Hib vaccine
Combination vaccine
Meningococcal vaccine
Safety
Preterm/full-term infants
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-01-04
Enrollment: 313
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase IIIb study is to evaluate the immunogenicity, reactogenicity \& safety of GSK Biologicals' Hib-MenC vaccine (Menitorix™) when co-administered with GSK Biologicals' DTPa-HBV-IPV vaccine (Infanrix™ penta) \& Wyeth's 7-valent pneumococcal conjugate vaccine (Prevenar™) in preterm infants as a 3-dose primary vaccination course during the first 6 months of life (at 2, 4, 6 months of age) and of a booster dose of Menitorix™ when co-administered with GSK Biologicals' DTPa-IPV vaccine (Infanrix IPV) and Wyeth's Prevenar in the second year of life (16-18 months of age). The control is a group of full-term infants receiving the same vaccines. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: This multicenter study is open \& consists of a primary \& a booster phase. The study has 2 treatment groups (Preterm \& Full-term) that will receive the same vaccinations; the Full-term group will be the active control. Four blood samples will be collected from all subjects for immunogenicity analyses; 2 in the primary phase at prior to the first vaccination and one month after the third vaccination and 2 in the booster phase at prior to booster dose and one month after booster dose.

Eligibility criteria: Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

* 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 and 12 weeks of age at the time of the first vaccination.
* Written informed consent obtained from the parent or guardian of the subject.

All preterm subjects must satisfy the following criteria at study entry:

* Born after a gestation period of less than or equal to 36 weeks (≤258 days).
* Medically stable, i.e. do not require significant medical support or ongoing management for debilitating disease and have demonstrated a clinical course of sustained recovery.

All full-term subjects must satisfy the following criteria at study entry:

* Born after a gestation period between and including 37 and 42 weeks (≥259 days and ≤294 days).
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

* 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 of immunosuppressants or other immune-modifying drugs since birth.
* Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of vaccine until the last study visit, except measles-mumps-rubella (MMR) and varicella vaccines which may be given according to local immunisation practices and except rotavirus oral vaccine which is allowed at anytime during the study after hospital discharge as per prescribing information.
* Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, meningococcal serogroup C and or Streptococcus pneumoniae disease, with the exception of hepatitis B vaccine or BCG vaccine given in the first month of life according to the national recommendations (although BCG and hepatitis B vaccines should have been given outside a 30-day window from the first administration of study vaccines).
* History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
* A family history of congenital or hereditary immunodeficiency.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
* Major congenital defects or serious chronic illness.
* History of any neurologic disorders or seizures.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins (with the exception of monoclonal antibodies against respiratory syncytial virus \[RSV\]) and/or any blood products within one month (30 days) preceding the first dose of study vaccines.
* Planned administration of immunoglobulins and/or any blood products during the active phase of the study.

Specific criteria for the booster part of the study (to be checked at Visit 5, study month 14):

* History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
* Previous vaccination, except the study vaccines and hepatitis birth dose, against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.
* Previous booster vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and/or S. pneumoniae disease.

Primary outcomes:
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL)
timeFrame: One month after the third vaccination
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:8
timeFrame: One month after the third vaccination
Secondary outcomes:
measure: Number of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to the Cut-off Values
timeFrame: Before vaccination (at Day 0)
measure: Number of Subject With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1 Microgram Per Milliliter
timeFrame: One month after the third vaccination
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
timeFrame: Before vaccination (at Day 0)
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
timeFrame: One month after the third vaccination
measure: Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
timeFrame: Before vaccination (at Day 0)
measure: Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
timeFrame: One month after the third dose
measure: Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
timeFrame: Before vaccination (at Day 0)
measure: Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
timeFrame: One month after the third dose
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
timeFrame: Before vaccination (at Day 0)
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
timeFrame: One month after the third dose
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
timeFrame: Before vaccination (at Day 0)
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
timeFrame: One month after the third dose
measure: Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
timeFrame: Before vaccination (at Day 0)
measure: Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
timeFrame: One month after the third dose
measure: Number of Subjects Reporting Solicited Local Symptoms
timeFrame: During the 4-day follow-up period after any primary vaccination dose
measure: Number of Subjects Reporting Solicited General Symptoms
timeFrame: During the 4-day follow-up period after any primary vaccination dose
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days after each primary vaccination
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: Throughout the entire primary vaccination phase
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Migrogram Per Milliliter (µg/mL)
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1.0 Migrogram Per Milliliter (µg/mL)
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to the Cut-off Values
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to the Cut-off Values
timeFrame: Prior to (Month 14) the booster vaccination
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
timeFrame: Prior to (Month 14) the booster vaccination
measure: Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
timeFrame: Prior to (Month 14) and one month after the booster vaccination (Month 15)
measure: Number of Subjects Reporting Solicited Symptoms (Local and General)
timeFrame: During the 4-day follow-up period following booster vaccination
measure: Number of Subjects Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days after the booster vaccination (month 15)
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: 31 days after last primary vaccination until administration of booster dose (Month 14) and from the administration of the booster dose until the end of the study (Month 15)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Getafe
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
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: