E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of infections caused by Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, poliovirus type 1, 2 and 3, prevention against invasive infections caused by Haemophilus influenzae type b and infection caused by hepatitis B virus |
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E.1.1.1 | Medical condition in easily understood language |
Active immunisation against diphtheriae, tetanus, pertussis, hepatitis B, 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the immunogenicity of the study vaccine in terms of seroprotection (diphtheria toxoid, tetanus toxoid, poliovirus types 1, 2, and 3, Haemophilus influenza type b [Hib] polysaccharide [PRP], hepatitis B [Hep B]) and vaccine response for pertussis antigens (pertussis toxoid [PT] and filamentous haemagglutinin [FHA]) one month after the third dose |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity
To further describe the immunogenicity of the study vaccine, before the first dose and one month after the third dose
Safety
To describe the safety after each and any doses 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 between 42-56 days (6 to 8 weeks) 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 any 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 HBsAg seronegative mother (documented laboratory result of HBsAg assay from maternal blood sample performed during
last trimester of pregnancy available)
6) Have received one documented dose of Hep B vaccine and OPV from birth as per 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 another clinical trial 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 the first trial vaccination (except BCG vaccine) or planned receipt of any other
vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination
3) Previous vaccination against the diphtheria, tetanus, pertussis, poliomyelitis (expect the birth dose of OPV as per national
recommendations) and hepatitis B (except the birth dose of Hep B vaccine) diseases or Hib infection with 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) History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib infections (confirmed either clinically, serologically or
microbiologically)
7) Known personal or maternal history of HIV or hepatitis C seropositivity
8) Known 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
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 (axillary
temperature ≥38°C) on the day of inclusion (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, relatives 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 vaccine (D90, Visit 4, at approximately 18 weeks of age):
• Anti-diphtheria antibody (Ab) concentrations ≥ 0.01 International Units (IU)/mL
• Anti-tetanus Ab concentrations ≥ 0.01 IU/mL
• Anti-PRP Ab concentrations ≥ 0.15 μg/mL
• Anti-poliovirus 1, 2 and 3 Ab titers ≥ 8 (1/dilution [dil])
• 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 x LLOQ
• anti-Hep B Ab concentrations ≥ 10 mIU/mL |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoints were evaluated one month after the third dose of study vaccine (Day 90, Visit 4, at approximately 18 weeks of age). |
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E.5.2 | Secondary end point(s) |
Immunogenicity:
At baseline (Day 0, Visit 1), before the first dose:
1) Anti-diphtheria Ab concentrations ≥ 0.01 and 0.1 IU/mL
2) Anti-Hep B Ab concentrations ≥ 10 mIU/mL
3) Pertussis (PT, FHA) Ab concentrations ≥ LLOQ
4) Individual diphtheria, Hep B, PT and FHA antibody concentrations/titers
One month after the third dose of study vaccine (Day 90, Visit 4, at approximately 18 weeks of age):
5) Anti-diphtheria Ab concentrations ≥ 0.1 IU/mL
6) Anti-tetanus Ab concentrations ≥ 0.1 IU/mL
7) Anti-PRP Ab concentrations ≥ 1.0 μg/mL
8) Individual Abs concentrations/titers: all Abs
9) ≥ 4-fold and ≥ 2-fold increase in anti-PT and anti-FHA Ab
concentrations (EU/mL) from pre-dose 1 (Visit 1) to one month postdose 3 (Visit 4)
10) Anti-PT and anti-FHA Ab concentrations ≥ 5 EU/mL, ≥ 10 EU/mL and ≥ 25 EU/mL
11) Individual post-/pre-primary vaccination Ab concentration (EU/mL) ratios for all Abs
Safety:
12) Occurrence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after each and any vaccination(s).
13) Occurrence of solicited (prelisted in the subject’s diary card [DC] and Case Report Form) injection site and systemic reactions occurring through 7 days (D0-D7) following each and any vaccination(s).
14) Occurrence of unsolicited AEs through 30 days following each and any vaccination(s).
15) Occurrence of serious adverse events (SAEs) throughout the trial, Visit 1 to Visit 4.
Other endpoints recorded or derived will be described at the time of
statistical analysis. Depending on the item, these could include : nature
(Medical Dictionary for Regulatory Activities preferred term), time of onset,
duration, number of days of occurrence, grade of severity, relationship to
vaccine, action taken, whether the |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity:
Endpoints 1 through 4: Baseline (Day 0, Visit 1)
Endpoints 5 through 11: One month after the third dose of study vaccine (Day 90, Visit 4, at approximately 18 weeks of age)
Safety:
Endpoint 12: 30 minutes after each and any vaccination
Endpoint 13: Day 0 up to Day 7 post each and any vaccination
Endpoint 14: Day 0 up to Day 30 post each and any vaccination
Endpoint 15: Day 0 up to Day 90 |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |