E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diphtheria, Tetanus, Pertussis, Haemophilus Influenzae Type b infection, Poliomyelitis, and Hepatitis B
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E.1.1.1 | Medical condition in easily understood language |
Diphtheria, Tetanus, Whooping cough, Haemophilus Influenzae, Polio, and Hepatitis B |
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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 |
To demonstrate the non-inferiority in terms of seroprotection (Diphtheria, Tetanus, poliovirus types 1, 2, and 3, PRP-T, Hepatitis B) and vaccine response for pertussis antigens (pertussis toxoid [PT] and filamentous haemagglutinin [FHA]) of Group A (DTaP-IPV-Hep B-PRP-T combined vaccine) versus Group B (DTaP-IPV//PRP~T vaccine [Pentaxim]), one month after the third dose of combined vaccines. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity:
To further study the immunogenicity of the two vaccination schemes, before the first dose and one month after the last dose of vaccines.
Safety:
To study the safety after each and any dose of vaccines administered in the two vaccination schemes |
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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 30 to 40 days on the day of the first study visit
2) Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥2.5 kg
3) Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative
4) Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
5) Born to known hepatitis B surface antigen (HBsAg) seronegative mother: documented HBsAg negative status during the last trimester of pregnancy (or post-birth) or documented HBsAg negative and HBsAb positive status before last trimester of pregnancy
6) Have received one documented dose of Hep B vaccine at birth according to the national recommendations |
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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 the 4 weeks preceding the trial inclusion or planned participation during the present trial period in another clinical trial
investigating a vaccine, drug, medical device, or medical procedure
2) Receipt of any vaccine in the 4 weeks preceding any trial vaccination (except Bacille Calmette Guerin [BCG] vaccine) or planned receipt of any vaccine in the 8 days following any trial vaccination
3) Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B (except the dose of Hep B vaccine given at birth) diseases or Haemophilus influenzae type b infection with either the trial vaccine or another vaccine
4) Past or current receipt of immune globulins, blood or blood-derived products or planned administration during the trial
5) Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, since birth; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks since birth)
6) Known personal or maternal history of Human Immunodeficiency Virus (HIV) or hepatitis C seropositivity
7) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Haemophilus influenzae type b infection, confirmed either clinically,
serologically, or microbiologically
8) Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
9) Known thrombocytopenia, as reported by the parent/legally acceptable representative
10) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
11) In an emergency setting, or hospitalized involuntarily
12) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
13) Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
14) Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study
15) History of seizures |
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E.5 End points |
E.5.1 | Primary end point(s) |
One month after the third dose of study combined vaccines (Day 180, Visit 5, at approximately 7 months of age):
• anti-Diphtheria antibody (Ab) concentrations ≥ 0.01 International Units (IU)/mL
• anti-Tetanus Ab concentrations ≥ 0.1 IU/mL
• anti-PRP Ab concentrations ≥ 0.15 μg/mL
• anti-poliovirus 1, 2, and 3 Ab titers ≥ 8 (1/dilution [dil])
• ≥ 4-fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from 1 month pre-dose 1 (Visit 1) to 1 month post-dose 3 (Visit 5)
• anti-Hepatitis B Ab concentrations ≥ 10 mIU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One month post-dose 3 of study combined vaccines (Day 180) |
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E.5.2 | Secondary end point(s) |
Immunogenicity:
At Day 0 (Visit 1, at 1 month of age), before the first dose of vaccines:
• anti-Diphtheria Ab concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL
• anti-Hepatitis B Ab concentrations ≥ 10 mIU/mL
• individual Ab concentrations: anti-PT, anti-FHA, anti-Hep B, anti-D
• anti-PT and anti-FHA Ab concentrations ≥ LLOQ
One month after the third dose of study vaccine (Day 180, Visit 5, at approximately 7 months of age):
• anti-Diphtheria Ab concentrations ≥ 0.1 IU/mL
• anti-Tetanus Ab concentrations ≥ 0.01 IU/mL
• anti-PRP Ab concentrations ≥ 1.0 μg/mL
• vaccine response for PT and FHA antigens defined as post-dose 3 anti-PT and anti-FHA Ab concentrations in ELISA units (EU)/mL ≥ 4 x lower limit of quantitation (LLOQ) if pre-vaccination concentration is < 4 x LLOQ or ≥ pre-vaccination concentration if pre-vaccination concentrations ≥ 4 xLLOQ
• ≥ 2-fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from 1 month pre-dose 1 (Vis it 1) to 1 month post-dose 3 (Visit 5)
• anti-PT and anti-FHA Ab concentrations ≥ 5 EU/mL, ≥ 10 EU/mL, and ≥ 25 EU/mL
• individual antibody concentrations/titers: all antibodies
• individual post-/pre-primary vaccination Ab concentration ratios for anti-PT, anti-FHA, anti-Hep B, and anti-D
Safety:
• Occurrence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after each and any vaccination
• Occurrence of solicited (prelisted in the subject’s diary card and electronic Case Report Form [CRF]) injection site and systemic reactions occurring through 7 days (Day 0 to Day 7) after each and any vaccination
• Occurrence of unsolicited AEs up to 30 days after each and any vaccination, as well as up to 30 days after Visit 1 for subjects in Group A
• Occurrence of serious adverse events (SAEs) throughout the trial |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity:
Pre-dose (Day 0) and 1 month post-dose 3 of study combined vaccines (Day 180)
Safety:
Unsolicited systemic adverse events, 30 minutes post-each and any vaccination
Solicited injection site and systemic reactions, Day 0 up to Day 7 post-each and any vaccination
Unsolicited AEs, Day 0 up to Day 30 post-each and any vaccination
Serious adverse events, Day 0 up to Day 180 post-each and any vaccination |
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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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
DTaP-IPV//PRP~T combined vaccine (Pentaxim) and Recombinant hepatitis B monovalent vaccine (Euvax B) |
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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 |
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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 months | 6 |