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%.
refer to 10PN-PD-DIT-043 study (EudraCT number : 2008-005149-48) |
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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 of 10Pn-PD-DiT within first 7 months of life in clusters assigned to a 2-dose primary vaccination course
Criteria: see Main objective
•Effectiveness in preventing culture-confirmed/probable ID, reducing hospital-diagnosed pneumonia and impact on tympanostomy tube placement & outpatient antimicrobial prescriptions in combination with study 10PN-PD-DIT-043 (EudraCT number: 2008-005149-48)
•Impact on nasopharyngeal carriage of S. pneumoniae, H. influenzae and/or other bacterial pathogens, on acute otitis media in children starting vaccination <18 months of age (MOA)
•Impact on lower and upper respiratory tract infections, including acute otitis media in children starting vaccination <18 MOA (Turku subset)
•Immuno in children who received age-appropriate vaccination schedule
•Safety/reacto in children starting vaccination <18 MOA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects who the investigator believes that their parent(s)/guardian(s) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.
• 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 parent(s) or from the guardian(s) of the subject.
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E.4 | Principal exclusion criteria |
• Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the first dose of study vaccine, or planned use of such a vaccine other than the study vaccine(s) during the entire study period.
• Previous vaccination with any registered, non-registered or investigational pneumococcal vaccine, or planned use of such a vaccine other than the study vaccine 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.
refer to 10PN-PD-DIT-043 study (EudraCT number : 2008-005149-48) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from administration of 1st 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 assigned to a 2-dose primary vaccination course: occurrence of culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.
refer to 10PN-PD-DIT-043 study (EudraCT number : 2008-005149-48)
• Occurrence of culture-confirmed/probable ID due to any bacterial pathogen
• Occurrence of hospital-diagnosed pneumonia, tympanostomy tube placements, outpatient antibiotic prescriptions
• Antimicrobial susceptibility of S. pneumoniae & H. influenzae isolated from ID
• Occurrence of H. influenzae, S. pneumoniae and/or other bacterial pathogens in the nasopharynx & acquisition of new H. influenzae and/or S. pneumoniae strains
• Concentration of antibodies & opsonophagocytic activity against components of the investigational pneumococcal conjugate vaccine (subset)
• Occurrence of acute otitis media (AOM), recurrent AOM, AOM by severity, AOM with documented antimicrobial prescription
• Occurrence of lower & upper respiratory tract infections, including AOM (Turku subset)
• Occurrence of solicited local/general adverse events (AE), unsolicited AEs, SAEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Culture-confirmed/probable ID: from administration of 1st vaccine dose up to study end
Culture-confirmed ID (in children starting vaccination within 1st 7 months of life): 2 weeks post-primary vaccination
Hospital-diagnosed pneumonia, tympanostomy, antibiotic prescriptions/susceptibility, AOM: from administration of 1st vaccine dose up to study end
Occurrence/acquisition: prior to 1st vaccination, 1 month post-dose 1 & post-dose 2, before booster dose, 3 months post-booster and at last scheduled visit
Immuno: 1 month post-dose 1, post-dose 2 & post-dose 3, before booster dose and at last scheduled visit
Solicited AEs: within 4 days after each vaccination
Unsolicited AEs: within 4 days after each vaccination
SAEs: following administration of 1st 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 | Yes |
E.6.13.1 | Other scope of the trial description |
immunogenicity and carriage |
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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) | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
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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Analysis in this study will be done not earlier than the time of unblinding in study 10PN-PD-DIT-043. Blinded study follow-up for invasive disease will end on 31 January 2012, after at least 30 months of follow-up from the 10PN-PD-DIT-043 study start. At the time of unblinding, all available cleaned data for completed visits will be analyzed and considered as final results. Potentially remaining procedures up to the last completed visits will follow after unblinding. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |