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
Overview
- Phase
- Phase 3
- Intervention
- Pneumococcal conjugate vaccine GSK1024850A.
- Conditions
- Infections, Streptococcal
- Sponsor
- GlaxoSmithKline
- Enrollment
- 750
- Locations
- 1
- Primary Endpoint
- Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
Intervention: Pneumococcal conjugate vaccine GSK1024850A.
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
Intervention: Infanrix hexa.
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
Intervention: Paracetamol.
Synflorix II Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment
Intervention: Pneumococcal conjugate vaccine GSK1024850A.
Synflorix II Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment
Intervention: Infanrix hexa.
Synflorix PRE Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
Intervention: Pneumococcal conjugate vaccine GSK1024850A.
Synflorix PRE Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
Intervention: Infanrix hexa.
Synflorix POST Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
Intervention: Pneumococcal conjugate vaccine GSK1024850A.
Synflorix POST Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
Intervention: Infanrix hexa.
Mencevax + Infanrix Hexa Group
Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine.
Intervention: Infanrix hexa.
Mencevax + Infanrix Hexa Group
Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine.
Intervention: Meningococcal vaccine GSK134612.
Outcomes
Primary Outcomes
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
Time Frame: Within 4 days (Day 0-3) after primary vaccine dose.
The cut-off for core fever was 38.0 degrees Celsius (ºC).
Secondary Outcomes
- Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off.(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Antibody Concentrations Against Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A)(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects Reported With Any and Grade 3 Solicited Local Symptoms.(During the 4-day (Days 0-3) post-primary vaccination period)
- Number of Subjects Reported With Serious Adverse Events (SAEs)(Throughout the entire study period (Month 0-Month 12))
- 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.(Up to 6 months after vaccination with Mencevax™)
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off(Within 4 days (Day 0-3) after primary vaccination dose)
- Concentrations of Antibodies Against Protein D (Anti-PD)(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects With Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay (rSBA) Titres ≥ the Cut-off Values(Prior to vaccination (PRE), 1 month (M1) and 12 months (M12) post-vaccination)
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)(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))
- Number of Subjects Reported With Unsolicited Adverse Events (AEs)(Within 31 days (Days 0-30) after primary vaccine dose.)
- Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations(12 month post-vaccination (M12))
- Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations(1 month post-vaccination (M1))
- Number of Subjects Reported With Any, Grade 3 and Related Solicited General Symptoms(During the 4-day (Day 0-3) post-vaccination period)
- Number of Subjects With Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers in the Mencevax + Infanrix Hexa Group(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.)
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)(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))
- Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T).(1 month post-vaccination (M1))
- Anti-poliovirus (Anti-Polio) Type 1, 2 and 3 Titers(12 month post-vaccination (M12))
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Vaccine Serotypes)(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))
- Number of Nasopharyngeal Swabs With H. Influenzae(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))
- Number of Subjects With New Acquisition Associated to S. Pneumoniae Detected in Nasopharyngeal Swabs(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))
- Number of Subjects With New Acquisition Associated to H. Influentzae Detected in Nasopharyngeal Swabs.(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))
- Number of Subjects With Anti-polysaccharide N (Anti-PS) Concentrations ≥ the Cut-off Values(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination)
- Geometric Mean Antibody Concentration (GMCs) for Anti-polysaccharide N (Anti-PS) Antibody Concentrations(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.)
- Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations in the Mencevax + Infanrix Hexa Group(Prior to vaccination (Pre))
- Number of Nasopharyngeal Swabs With S. Pneumoniae and H. Influenzae(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))
- Anti-tetanus Toxoids (Anti-T) Antibody Concentrations in the Mencevax + Infanrix Hexa Group(Prior to vaccination (Pre))
- Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations(1 month post-vaccination (M1))
- Anti-poliovirus (Anti-Polio) Types 1, 2 and 3 Titers(1 month post-vaccination (M1))