E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of infections caused by Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, poliovirus types 1, 2 and 3, prevention against invasive infections caused by Haemophilus influenzae type b and infection caused by hepatitis B virus |
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E.1.1.1 | Medical condition in easily understood language |
Active immunisation against diphtheria,tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021430 |
E.1.2 | Term | Immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036897 |
E.1.2 | Term | Prophylactic vaccination |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10021431 |
E.1.2 | Term | Immunisations |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10043413 |
E.1.2 | Term | Therapeutic procedures and supportive care NEC |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Immunogenicity
- To describe the antibody (Ab) persistence at 15 to 18 months of age for all valences following a three-dose primary series vaccination of either DTaP-IPV-Hep B-PRP-T or Pentaxim™ + Engerix™ B at 2, 3, and 4 months of age
- To describe the immunogenicity of a booster dose of DTaP-IPV-Hep B-PRP-T given at 15 to 18 months of age
Safety
- To describe the safety profile after a booster dose of DTaP-IPV-Hep B-PRP-T given at 15 to 18 months of age |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Toddler previously included in Study A3L10 who completed the three dose primary series vaccination of either DTaP-IPV-Hep B-PRP-T or Pentaxim™ and Engerix™ B at 2, 3, and 4 months of age
2) Toddler of 15 to 18 months of age (range: 456 to 578 days of age inclusive)
3) Informed Consent Form signed by the parent(s) or other legal representative(s) and an institution official other than an Investigator
4) Able to attend all scheduled visits and to comply with all trial procedures |
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E.4 | Principal exclusion criteria |
1) Participation in another clinical trial in the 4 weeks preceding the booster vaccination
2) Planned participation in another clinical trial during the present trial period
3) Congenital or acquired immunodeficiency, and immunosuppressive therapy such as long term systemic corticosteroid therapy
4) Systemic hypersensitivity to any of the vaccine components or history of a life threatening reaction to a vaccine containing the same substances
5) Chronic illness at a stage that could interfere with trial conduct or completion
6) Blood or blood derived products received in the last 3 months
7) Any vaccination in the 4 weeks preceding the booster vaccination
8) Any vaccination planned until Visit 02
9) History of documented pertussis, tetanus, diphtheria, polio, Haemophilus influenzae type b or hepatitis B infection(s) (confirmed either clinically, serologically or microbiologically)
10) Previous booster vaccination against pertussis, tetanus, diphtheria, polio or Haemophilus influenzae type b, and hepatitis B infection(s)
11) Coagulopathy, thrombocytopenia, or a bleeding disorder contraindicating intramuscular vaccination
12) Any vaccine related SAE that occurred following the three dose primary series administration of the investigational vaccine or of the reference vaccine in Study A3L10
13) Febrile (temperature > or =38.0°C) or acute illness on the day of inclusion
14) Known contraindication to further vaccination with a pertussis vaccine, i.e.
- Encephalopathy
- Temperature >40.0°C within 48 hours following a vaccine injection, not due to another identifiable cause during the primary series
- Inconsolable crying that occurred for >3 hours within 48 hours following vaccine injection during the primary series
- Hypotonic hyporesponsive episode within 48 hours following vaccine injection during the primary series
- Seizures with or without fever within 3 days following vaccine injection |
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity
The following endpoints were used to assess the Ab persistence (for all valences) before the booster dose at Day 0 (Visit [V01]):
- Ab titers for each valence
- Ab titers above a cut-off:
- Anti-T Ab titers ≥0.01 IU/mL and ≥0.1 IU/mL
- Anti-D Ab titers ≥0.01 IU/mL and ≥0.1 IU/mL
- Anti-Hep Bs Ab titers ≥10 mIU/mL and ≥100 mIU/mL
- Anti-PRP Ab titers ≥0.15 μg/mL and ≥1.0 μg/mL
- Anti-polio titers ≥8 (1/dil)
- Anti-pertussis toxoid (PT) Ab titers ≥4 EU/mL
- Anti-filamentous hemagglutinin (FHA) Ab titers ≥4 EU/mL
The following endpoints were used to assess the booster responses at D30 (V02):
- Ab titers for each valence
- Ab titers above a cut-off:
- Anti-T Ab titers ≥0.01 IU/mL, ≥0.1 IU/mL, and ≥1.0 IU/mL
- Anti-D Ab titers ≥0.01 IU/mL, ≥0.1 IU/mL, and ≥1.0 IU/mL
- Anti-Hep Bs Ab titers ≥10 mIU/mL and ≥100 mIU/mL
- Anti-PRP Ab titers ≥0.15 μg/mL and ≥1.0 μg/mL
- Anti-polio titers ≥8 (1/dil)
- Anti-PT Ab titers ≥4 EU/mL
- Anti-FHA Ab titers ≥4 EU/mL
- Individual titer ratio for each valence (V02/V01)
- Seroconversion for anti-PT and anti-FHA, defined as:
- Anti-PT and anti-FHA ≥four-fold Ab titers increase from V01 to V02
- Booster response to pertussis (PT and FHA), defined as:
- Subjects whose pre-vaccination Ab concentrations were less than the Lower Limit Of Quantitation (<LLOQ) would demonstrate the booster response if they had post-vaccination levels ≥4 x LLOQ
- Subjects whose pre-vaccination Ab concentrations were ≥LLOQ but <4 x LLOQ would demonstrate the booster response if they had a four-fold response (i.e. post-/pre-vaccination ≥4)
- Subjects whose pre-vaccination Ab concentrations were ≥4 x LLOQ would demonstrate the booster response if they had a two-fold response (i.e. post-/pre-vaccination ≥2)
Safety
- Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), intensity grade, duration, and relationship to vaccination for any unsolicited systemic adverse events (AEs) reported in the 30 minutes after the booster dose
- Occurrence, time to onset, number of days of occurrence, and intensity grade of solicited (prelisted in the subject diary and CRF), injection site reactions and systemic reactions up to 7 days after the booster dose
- Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity grade, and relationship to vaccination (for systemic AEs only) of unsolicited (spontaneously reported) AEs up to 30 days after the booster dose
- Occurrence of any serious adverse events (SAEs) throughout the study (from V01 to 6 months after the booster vaccination). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A 5 mL blood sample (BL) was to be taken at V01 (BL1-V01) and V02 (BL2-V02).
All subjects who received the DTaP-IPV-Hep B-PRP-T vaccine were to be followed for safety up to 6 months after the booster dose. Subjects who received a booster dose of Pentaxim™ + Engerix™ B vaccines were to be followed for safety up to 1 month after vaccination.
Total duration of participation in the study was 180 to 210 days (including the 6-month safety follow-up). |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 23 |