Clinical trial NCT00496015: Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Conjugate Vaccine GSK1024850A
Official title: Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Vaccine GSK1024850A and DTPa-HBV-IPV/Hib Vaccine (Infanrix Hexa) and Assessment of Impact of Pneumococcal Vaccination on Nasopharyngeal Carriage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Streptococcus Pneumoniae Vaccines
Meningococcal disease
Carriage
Prophylactic antipyretic
Safety
Pneumococcal vaccine
Fever
Pneumococcal disease
Immunogenicity
Meningococcal vaccine
Booster vaccination
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-07-04
Enrollment: 750
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to assess if the rate of febrile reactions following the co-administration of a booster dose of pneumococcal conjugate vaccines with standard infant vaccines is lowered when paracetamol is given prophylactically and to assess the impact of pneumococcal conjugate vaccine on pneumococcal and H. influenzae nasopharyngeal carriage compared to control group receiving meningococcal conjugate vaccine (GSK134612).

This protocol posting deals with objectives \& outcome measures of the booster phase. The objectives \& outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00370318).

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 should be enrolled in the study.
* A male or female between, and including, 12-15 months of age at the time of the vaccination.
* Written informed consent obtained from the parent or guardian of the subject.
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Subjects in the unprimed group

• A male or female who previously participated in study 107017 and received 3 doses of pneumococcal conjugate vaccine GSK1024850A.

Exclusion Criteria:

For all subjects:

* 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
* Indication, other than specified in the protocol, for prophylactic antipyretic treatment.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the dose of study vaccines, or planned use during the entire study period.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the dose of study vaccines.
* Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the dose of study vaccines and up to one month after the dose of study vaccines.
* History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
* 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 and/or any blood products within three months preceding administration of the dose of study vaccines or planned administration during the study period.
* Subjects of which both parents have a history of atopia.
* Subject has received systemic antibiotic therapy for acute illness within 24 hours prior to the vaccination.
* Subject is likely to receive antipyretic treatment as a result of a concomitant illness or has been treated with paracetamol within the past 24 hours.

DTPa-HBV-IPV/Hib vaccine:

* Known hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio, hepatitis B and Hib vaccines or to any component of the vaccines.
* Encephalopathy.
* As with other vaccines, administration of DTPa-HBV-IPV/Hib should be postponed in subjects suffering from acute mild, moderate or severe illness.

For subjects in the AP-AP, AP-NAP and NAP groups:

• Administration of any pneumococcal, diphtheria, tetanus, pertussis, polio, hepatitis B and/or Haemophilus influenzae type b vaccines other than allowed and used in study 107017.

For subjects in the AP-AP group:

• Subject with any contraindication to treatment with paracetamol.

For subjects in the unprimed group:

* Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W-135 and/or Y.
* Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroups A, C, W-135 and/or Y.
* Planned administration of a hepatitis B vaccine not foreseen by the study protocol during the period starting one month after the dose of study vaccines and up to study end.
* Previous vaccination with tetanus toxoid containing vaccines including T, DTP, DT, DTP-IPV, DTP-HBV-IPV and Hib-TT vaccines six months prior to study entry.
* History of meningococcal disease due to serogroup A, C, W, or Y.
* Administration of any pneumococcal vaccine since birth.
* Full vaccination history since birth not available.

Primary outcomes:
measure: Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
timeFrame: Within 4 days (Day 0-3) after primary vaccine dose.
Secondary outcomes:
measure: Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off
timeFrame: Within 4 days (Day 0-3) after primary vaccination dose
measure: Number of Subjects Reported With Any and Grade 3 Solicited Local Symptoms.
timeFrame: During the 4-day (Days 0-3) post-primary vaccination period
measure: Number of Subjects Reported With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 4-day (Day 0-3) post-vaccination period
measure: Number of Subjects Reported With Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days (Days 0-30) after primary vaccine dose.
measure: Number of Subjects Reported With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study period (Month 0-Month 12)
measure: Number of Subjects Reported With AEs Resulting in Rash, New Onset of Chronic Illness (NOCI), Emergency Room (ER) Visits and Non-routine Physician Office Visits.
timeFrame: Up to 6 months after vaccination with Mencevax™
measure: Number of Subjects With Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off.
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Concentrations of Antibodies Against Protein D (Anti-PD)
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Antibody Concentrations Against Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A)
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A
timeFrame: Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination
measure: Number of Subjects With Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay (rSBA) Titres ≥ the Cut-off Values
timeFrame: Prior to vaccination (PRE), 1 month (M1) and 12 months (M12) post-vaccination
measure: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers in the Mencevax + Infanrix Hexa Group
timeFrame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
measure: Number of Subjects With Anti-polysaccharide N (Anti-PS) Concentrations ≥ the Cut-off Values
timeFrame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination
measure: Geometric Mean Antibody Concentration (GMCs) for Anti-polysaccharide N (Anti-PS) Antibody Concentrations
timeFrame: Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.
measure: Anti-tetanus Toxoids (Anti-T) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
timeFrame: Prior to vaccination (Pre)
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations in the Mencevax + Infanrix Hexa Group
timeFrame: Prior to vaccination (Pre)
measure: Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T).
timeFrame: 1 month post-vaccination (M1)
measure: Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
timeFrame: 1 month post-vaccination (M1)
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
timeFrame: 1 month post-vaccination (M1)
measure: Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations
timeFrame: 1 month post-vaccination (M1)
measure: Anti-poliovirus (Anti-Polio) Types 1, 2 and 3 Titers
timeFrame: 1 month post-vaccination (M1)
measure: Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations
timeFrame: 12 month post-vaccination (M12)
measure: Anti-poliovirus (Anti-Polio) Type 1, 2 and 3 Titers
timeFrame: 12 month post-vaccination (M12)
measure: Number of Nasopharyngeal Swabs With S.Pneumoniae (Vaccine Serotypes)
timeFrame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)
timeFrame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)
timeFrame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Nasopharyngeal Swabs With H. Influenzae
timeFrame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Nasopharyngeal Swabs With S. Pneumoniae and H. Influenzae
timeFrame: Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Subjects With New Acquisition Associated to S. Pneumoniae Detected in Nasopharyngeal Swabs
timeFrame: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
measure: Number of Subjects With New Acquisition Associated to H. Influentzae Detected in Nasopharyngeal Swabs.
timeFrame: 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall)
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Ostrava
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Praha 5
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
facility: GSK Investigational Site
city: Praha 9
country: Czechia
facility: GSK Investigational Site
city: Znojmo
country: Czechia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Prymula R, Siegrist CA, Chlibek R, Zemlickova H, Vackova M, Smetana J, Lommel P, Kaliskova E, Borys D, Schuerman L. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet. 2009 Oct 17;374(9698):1339-50. doi: 10.1016/S0140-6736(09)61208-3.
citation: Prymula R, Hanovcova I, Splino M, Kriz P, Motlova J, Lebedova V, Lommel P, Kaliskova E, Pascal T, Borys D, Schuerman L. Impact of the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) on bacterial nasopharyngeal carriage. Vaccine. 2011 Feb 24;29(10):1959-67. doi: 10.1016/j.vaccine.2010.12.086. Epub 2011 Jan 6.
citation: Prymula R et al. Does prophylactic paracetamol influence the effect of 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) on pneumococcal nasopharyngeal carriage? Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
citation: Prymula R et al. Effects on serotype 6A and 6B nasopharyngeal carriage following immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine. Abstract presented at the 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.
citation: Prymula R et al. Limited clinical benefit but reduced antibody responses to paediatric vaccines following prophylactic paracetamol administration. Abstract presented at the 4th Europaediatrics, Moscow, Russia, 03-06 July 2009.
citation: Prymula R et al. The 10-valent pneumococcal vaccine conjugated to protein-D (PHiD-CV) reduces nasopharyngeal carriage of Streptococcus pneumoniae (SP) vaccine serotypes in Czech children. Abstract presented at the 6th World Congress of the World Society for Pediatric Infectious Diseases (WSPID). Buenos Aires, Argentina, 19-22 November 2009.