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) |
|
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 |
|
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 |
|
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 |
|
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 vaccine response rates to acellular Pertussis antigens (PTxd, FHA) of sanofi pasteur’s DTacP-IPV//PRP~T combined vaccine versus sanofi pasteur’s DTacP-IPV (TETRAXIM™) and PRP~T (Act-HIB™) vaccines, one month after the three-dose primary vaccination. |
|
E.2.2 | Secondary objectives of the trial |
Immunogenicity: To assess the immunogenicity (in terms of seroprotection/seroconversion / vaccine response rates and GMTs) of the study and reference vaccines one month after the third dose.
Safety: To describe the safety after each dose of the study vaccines.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged 2 months (56 to 70 days) inclusive on the day of inclusion
2) Born at full term of pregnancy (≥37 weeks) and 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
|
|
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 or current or planned administration during the trial (including immunoglobulins).
7) Any vaccination in the 3 weeks preceding the first trial vaccination.
8) History of diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b 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 or Haemophilus influenzae type b infection with the trial vaccine or another vaccine.
11) Thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination
12) History of/current major neurological diseases or seizures.
13) Febrile illness (axillary temperature ≥ 38°C) or acute illness on the day of inclusion.
14) Known family history of congenital or genetic immuno-deficiency.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints used to evaluate the primary objective: (non-inferiority):
One month after the third dose of study combined vaccine (Visit 4, at approximately 7 months of age)
- anti-Diphtheria antibody titers ≥ 0.01 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-PRP antibody titer ≥ 0.15 μg/mL (Farr type RIA)
- anti-PT and anti-FHA antibody titers (EU/mL) ≥ 4-fold increase (ELISA)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Four visits (V) and 2 blood samples (BL) will be performed in all infants included for the antibody determinations. The expected total duration of follow-up (first visit to last visit) for a subject will be of approximately 5 months. |
|
E.5.2 | Secondary end point(s) |
Immunogenicity:
One month after the third dose of study combined vaccine (Visit 4, at approximately 7 months of age)
- anti-Diphtheria antibody titers ≥ 0.1 IU/mL (Seroneutralization)
- anti-Tetanus antibody titers ≥ 0.01 IU/mL (ELISA)
- anti-PRP antibody titers ≥ 1.0 μg/mL (Farr type RIA)
- 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)
*post-/pre- vaccination titers.
Safety:
The secondary endpoints for the safety evaluation are:
• The occurrence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after vaccination.
• The occurrence, time to onset, number of days of occurrence, and severity of the following solicited (terms pre-listed in the CRF) injection site reactions between D0 and D7 after each injection:
• Injection site tenderness
• Injection site erythema
• Injection site swelling
• The occurrence, time to onset, number of days of occurrence, and severityb of the following solicited systemic reactions between D0 and D7 after each injection:
• Fever
• Vomiting
• Crying abnormal
• Drowsiness
• Appetite lost
• Irritability
• The occurrence, nature (MedDRA [Medical Dictionary for Regulatory Activities] preferred term), time to onset, duration, severity, and relationship to vaccination of unsolicited adverse events between D0 and D30 after each injection.
• The occurrence, nature, relationship to vaccination and seriousness criterion of any SAE occurring throughout the trial, up to V04.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Four visits (V) and 2 blood samples (BL) will be performed in all infants included for the antibody determinations. The expected total duration of follow-up (first visit to last visit) for a subject will be of approximately 5 months. |
|
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 |
Immunogenicity
Non-inferiority |
|
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 | 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 years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |