E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers: indicated for primary vaccination in infants for active immunization against diphtheria, tetanus, pertussis and poliomyelitis. |
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E.1.1.1 | Medical condition in easily understood language |
Protection against diphtheria, tetanus, pertussis and poliomyelitis. |
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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 |
|
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 |
|
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 assess immunogenicity in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3) and seroconversion/vaccine response rates to acellular Pertussis antigens (PT, FHA) of sanofi pasteur’s DTacP-IPV (Tetraxim™) vaccine, one month after the booster dose given at 4 to 6 years of age. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity:
To describe the antibody persistence in terms of anti-pertussis antibody levels (anti-PT, and -FHA) and in terms of seroprotection rates and GMTs for Diphtheria, Tetanus, and Poliovirus types 1, 2 and 3, just before administration of the booster dose (at Visit 1) in all subjects at 4-6 years of age.
To assess immunogenicity in terms of seroprotection rates (Diphtheria, Tetanus, Polio types 1, 2 and 3) and seroconversion/ vaccine response rates to acellular Pertussis antigens (PT, FHA) of sanofi pasteur’s DTacP-IPV (Tetraxim™) vaccine, one month after administration of the booster dose given at 4 to 6 years of age according to the secondary endpoints below.
Safety:
To describe the safety after the booster dose of the study vaccine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
An individual must fulfill all of the following criteria in order to be eligible for trial
enrollment:
1) Aged 4-6 years inclusive on the day of inclusion
2) Child having completed the three-dose vaccination and the booster
vaccination with DTacP-IPV//PRP~T combined vaccine (Pentaxim™) of the study E2I34
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 |
An individual fulfilling any of the following criteria is to be excluded from trial enrollment:
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 or current or planned administration during the trial (including immunoglobulins)
7) Any vaccination in the 4 weeks preceding the trial vaccination
8) History of diphtheria, tetanus, pertussis, poliomyelitis infection (confirmed either clinically, serologically or microbiologically)
9) Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or HIV infection
10) Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis diseases infection with the trial vaccine or another vaccine after completion of previous study E2I34
11) Thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination
12) History of/current major neurological diseases or seizures
13) Febrile illness (temperature ≥ 38°C) or acute illness on the day of inclusion.
14) Serious or severe reaction after a previous dose of any vaccine containing pertussis antigen, such as
• encephalopathy (with or without convulsions) in the 7days following previous administration of a pertussis containing vaccine,
• temperature more than 39.5°C within 48 hours following vaccine injection, not due to another identifiable cause
• inconsolable crying equal or more than 3 hours within 48 hours following vaccine injection,
• hypotonic hyporesponsive episode within 48 hours following vaccine injection,
• seizures with or without fever within 3 days following vaccine injection.
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|
E.5 End points |
E.5.1 | Primary end point(s) |
One month after administration of the booster dose of the study combined vaccine (Visit 2):
• anti-Diphtheria antibody titers ≥ 0.1 IU/mL (Seroneutralization)
• anti-Tetanus antibody titers ≥ 0.1 IU/mL (ELISA)
• anti-Polio 1, 2 and 3 antibody titers ≥ 8 (1/dil) (Seroneutralization)
• anti-PT and anti-FHA antibody titers (EU/mL) ≥ 4-fold increase
(ELISA) from baseline (V01) to V02 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Two visits (V) and 2 blood samples (BL) will be performed in all infants included. Subjects will receive the study vaccine [sanofi pasteur’s DTacP-IPV vaccine (TETRAXIM™)] at 4 to 6 years of age (at visit 1).
For antibody determinations, a blood sample of approximately 5 mL will be taken in
all subjects:
• just before the booster dose (BL1-V01, at 4-6 years of age),
• one month after the booster dose (BL2-V02) |
|
E.5.2 | Secondary end point(s) |
Immunogenicity:
Just before the booster dose of the study combined vaccine (Visit 1):
• individual antibodies titers for all antigens
• anti-Diphtheria antibody titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL (Seroneutralization)
• anti-Tetanus antibody titers ≥ 0.01 IU/mL and ≥ 0.1 IU/mL (ELISA)
• 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)
One month after the booster dose of the study combined vaccine (Visit 2):
• individual antibodies titers for all antigens
• anti-Diphtheria antibody titers ≥ 0.01 IU/mL (Seroneutralization)
• anti-Tetanus antibody titers ≥ 0.01 IU/mL (ELISA)
• anti-PT and anti-FHA antibody titers (EU/mL) ≥ 2-fold increase (ELISA) from baseline (V01) to V02
• anti-PT and anti-FHA antibody titers ≥ 5 EU/mL, ≥ 10 EU/mL and ≥ 25 EU/mL (ELISA)
• individual titers ratios * : all antibodies
*post-/pre- vaccination titers.
Safety
The endpoints for the safety evaluation are:
1) Occurrence, intensity, and relationship to vaccination of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after vaccination
2) Occurrence, time to onset, number of days of occurrence and intensity of solicited (prelisted in the subject’s diary card and CRF) injection site and systemic reactions occurring up to 7 days after vaccination.
3) Occurrence, nature (MedDRA preferred term), duration, maximum intensity and relationship to vaccination (for systemic AEs only) of unsolicited |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Two visits (V) and 2 blood samples (BL) will be performed in all infants included. Subjects will receive the study vaccine [sanofi pasteur’s DTacP-IPV vaccine (TETRAXIM™)] at 4 to 6 years of age (at visit 1).
For antibody determinations, a blood sample of approximately 5 mL will be taken in
all subjects:
• just before the booster dose (BL1-V01, at 4-6 years of age),
• one month after the booster dose (BL2-V02) |
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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 |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 0 |
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 | 30 |