| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Active immunization of children from the age of 6 weeks up to 18 months of age at the time of first vaccination, against Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F and Haemophilus influenzae.
The immunization schedule will depend on the age at the time of the first vaccination.
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061353 |
| E.1.2 | Term | Pneumococcal infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061190 |
| E.1.2 | Term | Haemophilus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To demonstrate the effectiveness of 10Pn-PD-DiT vaccine in preventing culture-confirmed IPD due to vaccine pneumococcal serotypes in children vaccinated with at least one dose of 10Pn-PD-DiT within the first 7 months of life in clusters assigned to a 3-dose primary vaccination course.
Criteria for effectiveness:
Effectiveness (VE) in preventing culture-confirmed IPD due to the 10 vaccine serotypes will be demonstrated if the 2-sided p-value calculated for the null hypothesis H0 = {vaccine-type [VT] IPD VE = 0%} is lower than 5%. |
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| E.2.2 | Secondary objectives of the trial |
•Effectiveness in preventing culture-confirmed IPD due to vaccine pneumococcal serotypes in children vaccinated with at least 1 dose ≤7 mth of life in clusters with 2-dose primary vaccination
Criteria: see E.2.1
•Children vaccinated with at least 1 dose from 6 wks-18 mth of age & children starting vaccination ≤7 mth of life and who completed age-appropriate schedule, effectiveness in preventing culture-confirmed/probable ID caused by:
-any & each of vaccine/vaccine-related/other pneumococcal serotypes, H. influenzae types
-any other bacterial pathogen
•Children vaccinated with at least 1 dose from 6 wks-18 mth:
-impact on hospital-diagnosed pneumonia, tympanostomy tube placements (TTPs), outpatient antimicrobial prescriptions, LRTI, URTI
-S. pneumoniae/H. influenzae antimicrobial susceptibility
•Unvaccinated population, indirect effects on:
-culture-confirmed/probable ID, hospital-diagnosed pneumonia
-TTPs/outpatient antimicrobial prescriptions (≤7 yrs)
•Long-term effects |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: A phase III double-blind, cluster-randomized, controlled study to evaluate the impact on nasopharyngeal carriage, acute otitis media, immunogenicity and safety of GSK Biologicals’ 10-valent pneumococcal and non-typeable Haemophilus influenzae protein D conjugate vaccine in children below 18 months of age.
Date of protocol: 30 October 2008.
Objectives:
• For all subjects enrolled in this study, effectiveness in preventing culture-confirmed or probable cases of ID and in reducing hospital-diagnosed pneumonia cases and impacts on occurrence of tympanostomy tube placement and on outpatient antimicrobial prescriptions will be evaluated in combination with subjects enrolled in study 10PN-PD-DIT-043, using outcomes from the national registers, as described in the 10PN-PD-DIT-043 study protocol.
• To assess the impact of vaccination with GSK Biologicals’ 10-valent pneumococcal conjugate vaccine on the nasopharyngeal carriage of S. pneumoniae serotypes, H. influenzae and/or other bacterial pathogens, on acute otitis media in children below 18 months of age.
• To assess the impact of vaccination with GSK Biologicals’ 10-valent pneumococcal conjugate vaccine on the incidence of LRTI and URTI, including acute otitis media, in children below 18 months of age.
• To evaluate the immunogenicity of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine in children having received the age-appropriate vaccination schedule.
• Safety/reacto in children starting vaccination below 18mth |
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| E.3 | Principal inclusion criteria |
Selection criteria for municipalities:
Clusters are defined to encompass selected municipalities based on the agreement for study participation obtained from the health care centre responsible for the municipality primary health care and well-baby clinics.
Note:
1) Health care centres with remote location or low annual birth cohorts (for instance the Åland and Northern Lapland municipalities) may not be offered study participation.
2) In some selected municipalities where no collaboration with health care centres has been set up, there is opportunity for parent(s) to let their child participate in study 10PN-PD-DIT-053 and receive the same vaccination as in the current study.
Inclusion criteria for study participants:
• A male or female between, and including, 6 weeks to 18 months of age at the time of the first vaccination.
• Written informed consent obtained from the parent/guardian of the subject.
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| E.4 | Principal exclusion criteria |
• Previous vaccination with any registered, non-registered or investigational pneumococcal vaccine other than the study vaccine, or planned use during the study period. If a child belongs to a high risk group for pneumococcal infections (such as children with an anatomic or functional asplenia, HIV infection, chronic cardiac or respiratory disease (not asthma), diabetes, cochlear implant, CSF fistula or with significant immunodeficiency) for which a licensed pneumococcal conjugate vaccine is made locally available, the subject can not be enrolled in the study and should be referred to the specific immunization program.
• Previous vaccination against Hepatitis B virus with any registered, non-registered or investigational vaccine, or planned use of such a vaccine other than the study vaccine during the study period.
• Previous vaccination against Hepatitis A virus with any registered, non-registered or investigational vaccine, or planned use of such a vaccine other than the study vaccine during the study period.
• Known severe hypersensitivity to any component of the study vaccines, including neomycin.
• Any medical condition that would contraindicate the initiation of routine immunization outside a clinical trial context.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
In children starting vaccination within the first 7 months of life in clusters assigned to a 3-dose primary vaccination course :
• Occurrence of culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From the administration of the first vaccine dose up to study end. |
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| E.5.2 | Secondary end point(s) |
•In children starting vaccination within first 7 months of life in clusters with 2-dose primary vaccination course: occurrence of culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.
•Occurrence of culture-confirmed/probable ID due to any bacterial pathogen
•Occurrence of hospital-diagnosed pneumonia, TTPs, outpatient antimicrobial prescriptions
•Antimicrobial susceptibility of S. pneumoniae and H. influenzae isolated from ID (vaccinated children)
•Occurrence of upper and lower respiratory tract infections, including AOM (subset of vaccinated subjects in Turku area)
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| From the administration of the first vaccine dose up to study end. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
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| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial is not the last visit of the last subject since vaccination dates are not documented in study database for all subjects. They are documented in medical records at well-baby clinics.
The end of trial is defined as the last 6-monthly safety report send by the principal investigator based at the National Institute for Health and Welfare (THL) in Finland.
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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