E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers: active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive infections caused by Haemophilus influenzae type b (such as meningitis, septicaemia, cellulitis, arthritis, epiglottitis, pneumopathy, osteomyelitis) |
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E.1.1.1 | Medical condition in easily understood language |
Protection against diphtheria, tetanus, pertussis, 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 | 18.1 |
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 | 18.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
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 | 18.1 |
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.1.3 | 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 non-inferiority in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3, PRP) and seroconversion/vaccine response rates to Pertussis antigens (PT, FHA) of sanofi pasteur’s DTacP-IPV//PRP~T combined vaccine (PENTAXIM™) administered at 2, 3 and 4 months of age or administered at 3, 4 and 5 months of age versus commercially available Wuhan’s DTacP vaccine and sanofi pasteur’s Hib tetanus conjugate (Act-HIB™) and IPV (IMOVAX Polio™) monovalent vaccines, one month after the three-dose primary vaccination of the combined vaccine. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity:
To assess and describe in each group the immunogenicity (in terms of seroprotection / seroconversion / vaccine response rates and GMTs) of all antigens one month after the third dose of the study vaccine(s).
To assess and describe in each group the immunogenicity [in terms of seroprotection rates / seroconversion / vaccine response rates and GMTs] of all antigens, just before the booster dose (antibody persistence) and one month after the booster dose with the study vaccine(s).
Safety:
To describe in each group the safety profile after each dose. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged 2 months (60 to 74 days) inclusive on the day of inclusion
2) Born at full term pregnancy (≥ 36 weeks) with a birth weight ≥ 2.5 kg
3) Informed consent form signed by the parent(s) or other legal representative
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 trial inclusion
2) Planned participation in another clinical trial during the present trial period
3) Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy
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 in the past
7) Any vaccination performed or planned in the 4 weeks preceding the first trial visit (except BCG and Hepatitis B, which can not be given within 8 days before the first study visit)
8) Vaccination planned in the 4 weeks following any trial vaccination (except BCG and Hepatitis B, which can not be given within 8 days before or after the study vaccine(s) administration)
9) History of diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b infection (confirmed either clinically, serologically or microbiologically)
10) Clinical or serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or HIV infection
11) Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis diseases or Haemophilus influenzae type b infection with the trial vaccine or another vaccine
12) Thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination
13) History of/current seizures
14) Febrile illness (axillary temperature ≥ 37.1°C) or acute illness on the day of inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity:
One month after the third dose of study vaccine(s):
- anti-Diphtheria antibody titers ≥ 0.1 IU/mL (ELISA)
- anti-Tetanus antibody titers ≥ 0.1 IU/mL (ELISA)
- anti-PRP antibody titers ≥ 1.0 μg/mL (ELISA)
- anti-PT and anti-FHA antibody titers (EU/mL) ≥ 2-fold increase (ELISA)
- anti-PT and anti-FHA antibody titers ≥ 5 EU/mL, ≥ 10 EU/mL and ≥ 25 EU/mL (ELISA)
- individual antibodies titers: all antibodies
- individual titers ratios* : anti-FHA (EU/mL) and anti-PT (EU/mL) antibodies (ELISA).
Before and one month after the booster dose of the study vaccine(s):
- anti-PRP antibody titers ≥ 0.15 μg/mL and ≥ 1.0 μg/mL (ELISA)
- anti-Diphtheria antibody titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL (ELISA);
- anti-Tetanus antibody titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL
- anti-Polio 1, 2 and 3 antibody titers ≥ 8 (1/dil) (Seroneutralization).
-anti-PT and anti-FHA antibody titers ≥ 5 EU/mL, ≥ 10 EU/mL and ≥ 25 EU/mL (ELISA)
- individual antibody titers: all antibodies
One month after the booster dose of the study vaccine(s):
- anti-PT and anti-FHA antibody titers (EU/mL) ≥ 2- and 4-fold increase (ELISA)
- individual titers ratios *: anti-FHA (EU/mL) and anti-PT (EU/mL) antibodies (ELISA).
*titers ratio = post-primary vaccination titer/ pre-primary vaccination titer and post-booster dose titer/ pre-booster dose titer
Safety:
• The occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), duration, intensity, and relationship to vaccination of any unsolicited systemic Adverse Events (AEs) reported in the 30 minutes after each vaccination.
• The occurrence, time to onset, number of days of occurrence and intensity of the solicited (terms pre-listed in the CRF) injection site and systemic reactions between D0 and D7 after each injection.
• The occurrence, nature (MedDRA preferred term), time to onset, duration, intensity and relationship to vaccination of unsolicited (spontaneously reported) AEs after each injection until next study visit.
• The occurrence, nature, time to onset, duration, outcome, relationship to vaccination and seriousness of any SAE occurring throughout the trial.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For antibody determinations, 4 blood samples (BL) of 3~3.5 mL each will be taken in each group:
• before the first dose (BL01),
• one month after the third dose (BL02),
• just before the booster dose (BL03),
• one month after the booster dose (BL04).
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Non-inferiority
Immunogenicity |
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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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 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
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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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |