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 |
To demonstrate that the hexavalent DTaP-IPV-Hep B-PRP-T combined vaccine induces an immune response that is at least as good as the response following Infanrix hexa™ in terms of seroprotection rates to Hep B and PRP, 1 month after a three-dose primary series (at 2, 4, and 6 months), when co-administered with Prevnar™. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity:
To describe in each group the immunogenicity parameters of each vaccine component (for DTaP-IPV-Hep B-PRP-T and Infanrix hexa™) at V06.
Safety:
To describe the overall safety after each injection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Two-month-old infant (50 to 71 days old) on the day of inclusion, of either gender
2) Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥2.5 kg
3) Hepatitis B vaccination since birth
4) Informed consent form signed by one parent/legally acceptable representative and an independent witness if the parent/legally acceptable representative is illiterate
5) 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 first trial vaccination
2) Planned participation in another clinical trial during the present trial period
3) Systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or a vaccine containing the same substances
4) Congenital or acquired immunodeficiency, or immunosuppressive therapy such as long-term systemic corticosteroid therapy
5) Chronic illness at a stage that could interfere with trial conduct or completion
6) Blood or blood-derived products received since birth
7) Any vaccination in the 4 weeks preceding the first trial vaccination
8) Any planned vaccination (except trial vaccinations) during the trial
9) Documented history of pertussis, T, D, polio, Hib, hepatitis B or Streptococcus pneumoniae infection(s) confirmed either clinically, serologically, or microbiologically
10) Previous vaccination against pertussis, T, D, poliomyelitis, Hib infection(s) or Streptococcus pneumoniae
11) Known personal or maternal history of Human Immunodeficiency Virus (HIV), Hep B (HBsAg carrier), or Hepatitis C seropositivity
12) Known thrombocytopenia or bleeding disorder contraindicating IM vaccination
13) History of seizures
14) Febrile (rectal equivalent temperature ≥38.0°C) or acute illness on the day of inclusion |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints were the seroprotection rates as assessed 1 month after the third dose of the primary series (i.e. at V06), with seroprotection being defined as:
- Anti-Hep B antibody (Ab) titers ≥10 mIU/mL
- Anti-PRP Ab titers ≥0.15 μg/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples for immunogenicity testing were collected at Day 0 and Day 150. |
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E.5.2 | Secondary end point(s) |
Immunogenicity:
- Anti-T and anti-D Ab titers at V06 (7 months of age), titers ≥0.01 IU/mL, ≥0.1 IU/mL and ≥1.0 IU/mL at V06 for each group.
- Anti-Hep B Ab titers at V06 (7 months of age) and titers ≥100 mIU/mL at V06 for each group.
- Anti-PRP Ab titers at V06 (7 months of age), titers ≥1.0 μg/mL at V06 for each group.
- Anti-PT and anti-filamentous hemagglutinin (anti-FHA) Ab titers at V06 (7 months of age), titers ≥4 EU/mL at V06, ≥4-fold increase from baseline to V06, and individual titers ratio (V06/V01 [7/2 months of age]) for each group.
- Anti-polio 1, 2, and 3 Ab titers at V06 (7 months of age) and titers ≥8 (1/dil) for each group.
- Vaccine response to pertussis (PT and FHA) at V06, defined as: anti-PT or anti-FHA in EU/mL ≥LLOQ (=2 EU/mL) in initially seronegative infants, or at least persistence (post-titer ≥ pre-titer) of the Ab titer in initially seropositive (titer in EU/mL ≥LLOQ [=2 EU/mL]).
Safety:
- Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), duration, intensity, and relationship to vaccination for any unsolicited systemic AEs reported in the 30 minutes after each injection.
- Occurrence, time to onset, number of days of occurrence, and intensity for solicited (pre-listed in the subject diary and Case Report Form [CRF]) injection site reactions and systemic reactions occurring up to 7 days after each injection.
- Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity, and relationship to vaccination (for systemic AEs only) of unsolicited (spontaneously reported) AEs up to 30 days after each injection.
- Occurrence, nature (MedDRA preferred term), time to onset, duration, and relationship to vaccination of SAEs throughout the trial. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples for immunogenicity testing were collected at Day 0 and Day 150.
A phone call or a visit was arranged to collect information on any SAE occurring during the 6 months after the last vaccine administration.
Total duration of participation was 300 days (including a 6-month follow-up for SAE after dose 3). |
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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 | 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 | No |
E.8.1.5 | Parallel group | No |
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 | 2 |
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 | 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 | 1 |
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 | 28 |