| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pertussis, adsorbed diphtheria and tetanus toxoids, inactivated poliomyelitis and polysaccharide of H. influenza type b bound to tetanus toxoid |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pertussis, diphtheria, tetanus, polio, and polysaccharide of H. influenza type b bound to tetanus toxoid |
|
| 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 |
Primary Phase
1) To compare the post-Dose 3 immunogenicity of PEDIACEL to Infanrix–-IPV+Hib, when both are co-administered with Prevenar to infants at 2, 3 and 4 months of age.
2) To compare the post-Dose 3 immunogenicity of Prevenar co-administered with PEDIACEL to the post-Dose 3 immunogenicity of Prevenar co-administered with Infanrix-IPV+Hib, in infants at 2, 3 and 4 months of age.
3) To describe the post-Dose 3 pertussis antibody responses in both study groups.
Booster Phase
Not applicable |
|
| E.2.2 | Secondary objectives of the trial |
Primary Phase
1) To describe the safety of PEDIACEL and Infanrix–-IPV+Hib after each vaccination when they are co-administered with Prevenar to infants at 2, 3, 4 months of age.
2) To describe the post-Dose 3 antibody responses to all the antigens contained in PEDIACEL, Infanrix–-IPV+Hib and Prevenar vaccines.
Booster Phase
1) To describe the safety of PEDIACEL and Infanrix–-IPV+Hib after the Dose 4 (booster) vaccination when they are co-administered with Prevenar to infants and toddlers at 12 to 18 months of age
2) To describe the post-Dose 4 (booster) antibody responses to all the antigens contained in PEDIACEL, Infanrix-IPV+Hib, and Prevenar vaccines
3) To compare the post-Dose 4 (booster) immunogenicity of concomitant administration of PEDIACEL and Prevenar to concomitant administration of Infanrix-IPV+Hib and Prevenar vaccines |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A potential subject had to meet all of the following criteria to be considered for trial enrolment:
1. Infants 55 to 75 days old, inclusive on the day of first vaccination.
2. Born at full term of pregnancy (> 37 weeks).
3. ICF signed by the parent(s) or the legal guardian (according to local regulations).
4. Parent(s) or the legal guardian was able to read and write in the local language.
5. Parent(s) or the legal guardian was able to attend all scheduled visits and to comply with the study procedures. |
|
| E.4 | Principal exclusion criteria |
A potential subject meeting any of the following criteria was ineligible for trial
enrolment:
1. Presence of fever (defined as rectal body temperature ≥ 38.0°C) reported within the last 72 hours.*
2. Moderate or severe acute illness with or without fever.*
3. Participation in another clinical trial in the 30 days preceding first study vaccination.
4. Planned participation in another clinical trial during the present study period.
5. Received diphtheria, tetanus, pertussis, poliomyelitis, H. influenzae type b or a pneumococcal vaccine separately or in combination prior to study vaccination.
6. Received any vaccination during the following periods:
- from 30 days prior to Visit 1 (BS1+Vac1) up to and including Visit 4 (BS2)
- from 30 days prior to Visit 5 (BS3+Vac4) up to and including Visit 6 (BS4).
7. Congenital or acquired humoral/cellular immunodeficiency or immunosuppressive therapy such as long-term systemic corticosteroids therapy (≥ 2 mg/kg/day prednisone equivalent for ≥ 14 days) in the previous 30 days.
8. Systemic or local hypersensitivity to any of the study vaccine components (including neomycin, streptomycin, polymyxin B and formaldehyde).
9. History of life-threatening reaction(s) (such as encephalopathy, hypotonichyporesponsive episode (HHE), rectal body temperature ≥ 40.0°C, convulsions with or without fever) to any vaccine containing the same components as the study vaccines.
10. Blood or blood-derived products (immunoglobulins) received since birth.
11. Known human immunodeficiency virus seropositivity.
12. Known thrombocytopenia or other bleeding disorder contraindicating IM vaccination.
13. History of encephalopathy, seizures or progressive, evolving or unstable neurological condition.
14. Clinically significant findings on review of systems that might interfere with study vaccination or which, in the opinion of the Investigator, would interfere with the evaluation of the study vaccine/objectives or pose a health risk to the subject.
*The Investigator was to postpone the vaccination until the condition resolved. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Phase
The parameters for the primary endpoints were:
1. Proportion of subjects achieving one month (28-42 days) post-Dose 3 seroprotective titres to each of the following antigens:
- PRP (at the level of ≥ 0.15 μg/mL)
- Diphtheria toxoid (at the level of ≥ 0.01 IU/mL)
- Tetanus toxoid (at the level of ≥ 0.01 IU/mL)
- Poliovirus types 1, 2 and 3 (at a titre of ≥ 1:8 dilution [dil]).
2. Proportion of subjects achieving one month (28-42 days) post-Dose 3 seroprotective titers to each of the following pneumococcal serotypes: 4, 6B, 9V, 14, 18C, 19F and 23F (at the level of ≥ 0.35 μg/mL).
3. Proportion of subjects achieving one month (28-42 days) post-Dose 3 seroresponse (defined as seropositivity, i.e. antibodies above the assay cut-off point (lower limit of quantitation [LLOQ]) at one month post-Dose 3 in subjects with baseline antibodies below the cut-off point or at least persistence of baseline antibody concentration in subjects who were initially seropositive to each of the following pertussis antigens:
- Pertussis toxoid (PT)
- Filamentous haemagglutinin (FHA)
- Pertactin (PRN)
- Fimbriae types 2 and 3 (FIM).
Booster Phase
Not applicable |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1 month post-dose 3 for all primary endpoints |
|
| E.5.2 | Secondary end point(s) |
Primary Phase
The parameters for the secondary endpoints were:
Safety Assessment
1. The number and percentage of subjects with any of the following:
a) Solicited injection site reactions (tenderness, erythema and swelling) collected from Day 0 to Day 7 after each vaccination
b) Solicited systemic reactions (fever, vomiting, abnormal crying, drowsiness, loss of appetite and irritability) collected from Day 0 to Day 7 after each vaccination
c) Unsolicited adverse events (AEs) collected in the diary card for 28 days after each vaccination
d) Serious adverse events (SAEs) reported from the time the informed consent form (ICF) was signed and throughout the course of the study.
A diary card was used to record solicited reactions (Day 0 to Day 7) and unsolicited AEs (Day 0 to Day 28) after each vaccination.
Immunogenicity Assessment
2. a. Geometric mean titers (GMTs) for antibodies against all antigens (PRP, diphtheria toxoid, tetanus toxoid, PT, FHA, PRN, FIM, poliovirus types 1, 2 and 3, and pneumococcal serotypes: 4, 6B, 9V, 14, 18C, 19F and 23F) in both groups at one month (28-42 days) post-Dose 3.
b. Proportion of subjects achieving one month (28-42 days) post-Dose 3 seroprotective titres to each of the following antigens:
- PRP (at the level of ≥ 1.0 μg/mL)
- Diphtheria toxoid (at the level of ≥ 0.1 IU/mL)
- Tetanus toxoid (at the level of ≥ 0.1 IU/mL)
Booster Phase
1) Geometric mean titers (GMTs) for diphtheria toxoid, tetanus toxoid, pertussis antigens (PT, FHA, PRN, and FIM), PRP, poliovirus antigens (Type 1, 2 and 3), and pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F and 23F pre-Dose 4 and at one month (28-42 days) post-Dose 4 vaccination will be calculated by vaccine group.
2) Proportion of subjects with a booster response to pertussis antigens from pre-Dose 4 to one month (28-42 days) post-Dose 4 (booster) vaccination with respect to pre-Dose 4 vaccination:
- Pertussis toxoid
- Filamentous haemagglutinin
- Pertactin
- Fimbriae types 2 and 3
3) Proportion of subjects achieving one-month (28-42 days) post-Dose 4 vaccination seroprotective titres to each of the following antigens will be calculated by vaccine group and the difference in proportions between both groups and the 95% CI will be computed:
- PRP (at the level of ≥ 1.0 µg/mL)
- Diphtheria toxoid (≥ 0.1 IU/mL)
- Tetanus toxoid (at the level of ≥ 0.1 IU/mL)
- Polio 1, 2, and 3 (at a titre of ≥ 1:8 dil)
- Pneumococcal serotypes 4, 6B, 9V, 14, 18C 19F and 23F (at the level of ≥ 0.35 µg/mL) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Primary Phase
1a) Day 0 up to Day 7 post-each vaccination
1b) Day 0 up to Day 7 post-each vaccination
1c) Day 0 up to Day 28 post-each vaccination
1d) Day 0 up to Day 28 post-dose 3
Booster Phase
1) Pre-dose 4 and 1 month post-dose 4 (booster)
2) Pre-dose 4 and 1 month post-dose 4 (booster)
3) 1 month post-dose 4 (booster) |
|
| 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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial months | 17 |
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