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 the equivalence of three batches of DTaP-IPV-Hep B-PRP-T vaccine second Drug Product Generation in terms of seroprotection rates for D, T, Hep B, PRP, and polio and seroconversion rates for anti-pertussis toxoid (PT) and anti-filamentous hemagglutinin (FHA), 1 month after a three-dose primary series (at 2, 4, and 6 months of age). |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity
- To describe in each group, including the Infanrix hexa™ group, the immunogenicity parameters for all antigens, 1 month after the third dose of the primary series
- To demonstrate that the immune response of the DTaP-IPV-Hep B-PRP-T vaccine does not induce a lower immune response than the Infanrix hexa™ vaccine in terms of seroprotection to D (defined by a titer ≥0.01 IU/mL), 1 month after a third dose of the primary series
Safety
To assess the overall safety in each group 1 month after the third 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 AEs in the first 30 days after each injection
- Any serious adverse events (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 infants (50 to 71 days old) on the day of inclusion
2) Born at full term of pregnancy (> or =37 weeks) with a birth weight > or =2.5 kg
3) Informed Consent Form signed by one or both parents or by the guardian and two independent witnesses
4) Able to attend all scheduled visits and to comply with all trial procedures
5) 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 four weeks preceding the (first) trial vaccination
2) Planned participation in another clinical trial during the present trial period
3) Congenital or acquired immunodeficiency
4) 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
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 visit
8) Any planned vaccination (except BCG, rotavirus, and pneumococcal conjugated vaccines) during the study
9) Documented history of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b or hepatitis B infection(s) (confirmed either clinically, serologically or microbiologically)
10) Previous vaccination against hepatitis B, pertussis, tetanus, diphtheria, poliovirus, or Haemophilus influenzae type b infection(s)
11) Known personal or maternal history of HIV, hepatitis B (HBsAg) or hepatitis C seropositivity
12) Thrombocytopenia or a 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 following serological endpoints were assessed 1 month after the third dose of the primary series (V06, D150):
Seroprotection rates for D, T, Hep B, PRP, and polio were defined as:
- Anti-D and anti-T antibody (Ab) titers ≥0.01 IU/mL
- Anti-Hep B Ab titers ≥10 mIU/mL
- Anti-PRP Ab titers ≥0.15 μg/mL
- Anti-polio 1, 2, and 3 Ab titers ≥8 (1/dil)
Seroconversion rates for anti-PT and anti-FHA were defined as:
- Anti-PT and anti-FHA Ab titers ≥4-fold increase from baseline (V01) to V06 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A 4 mL blood sample was collected at 2 months of age (BL1-V01) and a 5 mL blood sample at 7 months of age (BL2-V06). |
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E.5.2 | Secondary end point(s) |
Immunogenicity
Endpoints for immune response (descriptive) included:
Endpoints included:
- Ab titers for each valence at V06 and anti-D Ab titers at V01
- Ab titers above a cut-off (V06):
- Anti-T Ab titers ≥0.1 IU/mL and ≥1.0 IU/mL
- Anti-D Ab titers ≥0.1 IU/mL and ≥1.0 IU/mL
- Anti-Hep Bs Ab titers ≥100 mIU/mL
- Anti-PRP Ab titers ≥1.0 μg/mL
- Anti-PT Ab titers ≥4 EU/mL
- Anti-FHA Ab titers ≥4 EU/mL
- Anti-D Ab titers ≥0.01 IU/mL, ≥0.1 IU/mL and ≥1.0 IU/mL at V01 and individual titer ratio (V06/V01)
- Response to pertussis (PT, FHA) antigens defined at V06 as anti-PT or anti-FHA ≥4 EU/mL in initially seronegative infants, or at least persistence (post-titer ≥ pre titer) of the Ab titer in initially seropositive infants (titer ≥4 EU/mL)
Safety
- Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term (PT), intensity, and relationship to vaccination for any unsolicited systemic AEs reported in the 30 minutes after each vaccination
- Occurrence, time to onset, number of days of occurrence, and intensity for solicited (prelisted in the subject diary and Case Report Form) injection site reactions and systemic reactions occurring up to 7 days after each vaccination
- Occurrence, nature (MedDRA PT), time to onset, duration, intensity, and relationship to vaccination (for systemic AEs only) for unsolicited (spontaneously reported) AEs up to 30 days after each vaccination
- Occurrence of any SAEs during the trial (including the 6-month follow-up after the last dose of the primary series) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A 4 mL blood sample was collected at 2 months of age (BL1-V01) and a 5 mL blood sample at 7 months of age (BL2-V06).
A phone call or a visit was arranged in order to collect information on any SAE occurring during the 6 months after the last vaccine administration.
Total duration of participation was 10 months for each subject (including the 6-month follow-up for SAEs 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 | 4 |
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 | 7 |