| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active immunization against hepatitis A, , diphtheria, tetanus, pertussis and Haemophilus influenza type B infections of healthy children 15 months of age at the time of the first study vaccination. |
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| E.1.1.1 | Medical condition in easily understood language |
Jaundice
Whooping cough
Tetanus
Diphtheria
Meningitis
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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 non-inferiority of the anti-HAV immune response (with respect to both seropositivity rates and GMCs) 31 days following the second dose of Havrix when the first dose of Havrix is co-administered with Infanrix and ActHIB (HAV+DTaP+HIB Group) compared to Havrix given alone (HAV Group).
To demonstrate the non-inferiority of the anti-diphtheria (D) and anti-tetanus (T) seroprotection rates; anti-pertussis (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) GMCs and vaccine response rates; and anti-polyribosylribitol phosphate (PRP) seroprotection rate 31 days following the co-administration of Infanrix and ActHIB with the first dose of Havrix (HAV+DTaP+HIB Group) compared to Infanrix and ActHIB given alone (DTaP+HIB→HAV Group).
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| E.2.2 | Secondary objectives of the trial |
Non-inferiority of the anti-PT, anti-FHA & anti-PRN im-mune response 31 days post the co-administration of In-fanrix and ActHIB with dose 1 of Havrix (HAV+DTaP+HIB Group) vs. Infanrix & ActHIB given alone (DTaP+HIB→HAV Group).
Anti-D, anti-T anti-PRP, anti-PT, anti-FHA, anti-PRN & anti-PRP immune responses 31 days post the co-administration of Infanrix & ActHIB with dose 1 of Havrix in the HAV+DTaP+HIB Group & the DTaP+HIB→HAV Group.
Anti-HAV immune response 31 days post dose 1 of Havrix in the HAV Group & the HAV+DTaP+HIB Group.
Vaccine response to Havrix 31 days fpost dose 2 of Havrix for all groups,
Incidence & intensity of solicited local and generalAEs during the 4-day (Days 0-3) period post each dose.
Incidence, nature, intensity & causal relationship to vac-cination of unsolicited AEs post each dose of study vac-cine(s) during the 31-day) follow-up period & SAEs NOCIs & MAEs in each group during the Active Phase & the ESFU of the study.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Only subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol should be enrolled in the study,
A male or female child 12 or 13 months of age [i.e., subjects who have achieved their 12-month birthday but not yet achieved their 14-month birthday] at the time of entry into the Enrollment Phase,
Subjects must have previously received three doses each of DTaP and Hib vaccines during the first year of life. The three doses of DTaP vaccine must have been administered as either Infanrix or Pediarix® and the three doses of Hib vaccine must have been administered as ActHIB, HibTITER®, OmniHIB®
Subjects who, at 15 months of age, will have had at least six months elapse since their third dose of Infanrix or Pediarix,
Written informed consent obtained from the parents or guardian of the subject,
Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and
Parents/guardian of the subject must have a telephone or be able to be contacted by telephone.
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| E.4 | Principal exclusion criteria |
Use of any investigational or non-registered drug or vaccine other than the study vaccin(s within 31 days preceding the first dose of study vaccine, or planned use during the study period,
Chronic administration of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period.
Planned administration or administration of any vaccine not foreseen by the study protocol during the period 42 days before and 31 days after each dose of study vaccines should be administered before or during the Enrollment Phase of the study but >= 42 days prior to administration of study vaccines at Day 0.
In order to comply with the ACIP-recommended admini-stration of Hib vaccine during the age range of 12-15 months, subjects in the HAV Group ONLY should receive their fourth dose of the Hib vaccine as commercially-available ActHIB during the interval between Visit 3 of the Active Phase and the subject's 19-month birthday.
Previous vaccination against DTaP using a commercially-available brand other than Infanrix or Pediarix or against Hib using a commercially-available brand other than ActHIB, HibTITER or OmniHIB.
Previous vaccination with more than three doses of DTaP-containing vaccines or more than three doses of Hib-containing vaccines.
Previous vaccination against hepatitis A,
History of hepatitis A,
Known exposure to hepatitis A,
History of diphtheria, tetanus, pertussis and/or Haemo-philus influenza type b,
Known exposure to diphtheria, tetanus, pertussis and/or Haemophilus influenza
type b within 31 days prior to the start of the study,
History of non-response to any vaccine in the current routine immunization schedule,
Any confirmed or suspected immunosuppressive or im-munodeficient condition, including human immunodefi-ciency virus infection,
A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection,
History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of Havrix, Infanrix or ActHIB including 2-phenoxyethanol, neomycin and gelatin,
History of hypersensitivity/allergic reaction to latex. Note: The tip cap and the rubber plunger of the Havrix and Infanrix needleless pre-filled syringes and the stopper of the ActHIB diluent vial contain dry natural latex rubber.
Major congenital defects or serious chronic illness,
History of any neurologic disorder.,
Acute disease at the time of vaccination.
Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period, i.e., the Enrollment Phase, the Active Phase and the Extended Safety Follow-up Phase.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Anti-HAV seropositivity rates and GMCs following the second dose of Havrix in the HAV Group and the HAV+DTaP+HIB Group.
Anti-D and anti-T seroprotection rates; anti-PT, anti-FHA and anti-PRN GMCs and vaccine responses; and anti-PRP sero-protection rate following the administration of Infanrix and ActHIB in the HAV+DTaP+HIB Group and the DTaP+HIB→HAV Group. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Visit 3 (Month 0) for both the groups.
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| E.5.2 | Secondary end point(s) |
Anti-D, anti-T and anti-PRP GMCs following the administration of Infanrix and ActHIB in the HAV+DTaP+HIB Group and the DTaP+HIB→HAV Group.
Anti-PT, anti-FHA, anti-PRN and anti-PRP seropositivity rates following the administration of Infanrix and ActHIB in the HAV+DTaP+HIB Group and the DTaP+HIB→HAV Group.
Anti-HAV GMCs and seropositivity rates following the first dose of Havrix in the HAV Group and the HAV+DTaP+HIB Group.
Anti-HAV GMCs and seropositivity rates following the second dose of Havrix in the DTaP+HIB→HAV Group.
Vaccine response to Havrix following the second dose in all three groups.
Incidence and intensity of solicited local AEs.
Incidence, intensity and causal relationship to vaccination of solicited general AEs.
Incidence, nature, intensity and causal relationship to vaccination of unsolicited AEs.
Incidence, nature, intensity and causal relationship to vaccination of SAEs, new chronic illnesses and medically significant events in each group.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
For anti-D, anti-T and anti-PRP GMCs and anti-PT, anti-FHA, anti-PRN and anti-PRP seropositivity rates: At Visit 3 (Month 0)
For anti-HAV GMCs and seropositivity rates and vaccine response rate: At Visit 5 (Month 7-10)
For solicited local and general symptoms: During the 4-day period (Days 0-3) following each dose of study vaccine(s) in each group.
For unsolicited AEs: During the 31-day period (Days 0-30) following each dose of study vaccine(s) in each group.
For SAEs: During the Active Phase (Month 0 to Month 11) and the Ex-tended Safety Follow-up Phase (Moth 11 to Month 16) |
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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 | No |
| 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) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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 | 3 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| 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 |
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