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, 1 month after a three-dose primary series (2, 4, and 6 months). |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity
To describe in each group the immunogenicity to D, PRP, and Hep B vaccine components (for DTaP-IPV-Hep B-PRP-T and Infanrix hexa™) 1 month after the third dose of the primary series.
Safety
To assess the overall safety in each group 1 month after each dose of the primary series in terms of the incidence rates of:
- Any unsolicited systemic adverse events (AEs) in the first 30 minutes after each injection
- Any solicited adverse reactions (ARs) in the first 7 days after each injection
- Any unsolicited AEs in the first 30 days after each injection
- Any SAEs during the trial (including the 6-month follow-up period) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Two months 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) Mother negative for HBsAg in approximately the last 30 days of pregnancy (≥36 weeks of amenorrhea) or in the 30 days post-partum
4) Informed consent form signed by both parents. If one or both parent(s) are under 18 years of age, the subject’s grandparent(s) should also sign. An independent witness should also sign if the parent(s)/grandparent(s) are illiterate
5) Able to attend all scheduled visits and to comply with all trial procedures
6) Received Bacillus Calmette-Guerin (BCG) vaccine between birth and 1 month of life in agreement with the national immunization calendar |
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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) Known 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 (for more than 2 weeks) systemic corticosteroid therapy within the last four weeks
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 during the trial (until V06), except the study vaccines, rotavirus vaccine, and pneumococcal conjugate vaccines
9) Documented history of pertussis, tetanus, diphtheria, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infection(s) (confirmed either clinically, serologically, or microbiologically)
10) Previous vaccination against pertussis, tetanus, diphtheria, poliomyelitis, hepatitis B or Haemophilus influenzae type b infection(s)
11) Known personal or maternal history of Human Immunodeficiency Virus, hepatitis B or hepatitis C seropositivity
12) Known thrombocytopenia or bleeding disorder contraindicating IM vaccination
13) History of seizures
14) Febrile (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 anti-Hep Bs antibody (Ab) titers were to be assessed 1 month after the third dose of the primary series (i.e. at V06) with seroprotection being defined as anti-Hep B Ab titers ≥10 mIU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A 4 mL blood sample was to be taken at 2 months of age (BL1 - V01) and a 5 mL sample at 7 months of age (BL2 - V06). |
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E.5.2 | Secondary end point(s) |
Immunogenicity
- Anti-D Ab titers at V01 and Ab titers for D, PRP, and Hep B antibodies at V06
(7 months of age).
- Ab titers above a cut-off (V01):
- Anti-D Ab titers ≥0.01 IU/mL, ≥0.1 IU/mL
- Ab titers above a cut-off (V06):
- Anti-D Ab titers ≥0.01 IU/mL, ≥0.1 IU/mL
- Anti-Hep Bs Ab titers ≥100 mIU/mL (note: a threshold of ≥10 mIU/mL, not specified in the protocol, was also analyzed)
- Anti- PRP Ab titers ≥0.15 μg/mL and ≥1.0 μg/mL
- Ab individual titers ratios for anti-D (V06/V01)
Safety
- Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term [PT]), duration, severity, 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 severity for solicited (pre-listed in the subject diary and Case Report Form) injection site reactions and systemic reactions occurring up to 7 days after each injection
- Occurrence, nature (MedDRA PT), time to onset, duration, severity, and relationship to vaccination (for systemic AEs only) of unsolicited (spontaneously reported) AEs up to 30 days after each injection
- SAEs throughout the trial (including the 6-month follow-up period) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A 4 mL blood sample was to be taken at 2 months of age (BL1 - V01) and a 5 mL sample at 7 months of age (BL2 - V06).
The total study participation for each subject was expected to be 10 months, with a safety follow-up being conducted 6 months after the last vaccination. |
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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?
| 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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 19 |