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 types 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 diphtheria,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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 14.1 |
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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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.1.3 | 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 equivalence of immunogenicity on three lots of DTaP-IPV-Hep B-PRP-T vaccine (final bulk product [FBP]) one month after a three-dose primary series (2, 4 and 6 months) when co-administered with Prevenar™ and Rotarix™ , in terms of immunoresponses evaluated by:
- Geometric Means of Titers (GMTs) for Hep B.
- Seroprotection rates for D, T, Hep B, PRP, and polio and seroresponse rates for anti-PT and anti-FHA.
- To demonstrate the non-inferiority of the hexavalent DTaP-IPV-Hep B-PRP-T vaccine to the licensed hexavalent Infanrix hexa™ vaccine in terms of seroprotection or seroresponse rates to all antigens, one month after a three-dose primary series when co-administered with Prevenar™ and Rotarix™. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity
- To describe in each group the immunogenicity parameters for all antigens for each vaccine
Safety
To assess the safety profile in each group, for each vaccine, in terms of incidence of:
- Unsolicited systemic adverse events (AEs) in the first 30 minutes after each injection.
- Solicited injection site (except Rotarix™) and systemic adverse reactions (ARs) in the first 7 days after each injection.
- Unsolicited non-serious AEs in the first 30 days after each injection.
- Serious adverse events (SAEs) during the trial (including the 6-month follow-up period). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Two-month old infants (55 to 65 days of age) on the day of inclusion.
2) Born at full term of pregnancy (≥37 weeks) with a birth weight ≥2.5 kg.
3) Informed consent form signed by one or both parents or by the legally acceptable representative as per local requirements.
4) Able to attend all scheduled visits and to comply with all trial procedures.
5) Received Hep B and Bacille de Calmette-Guérin (BCG) vaccines between birth and one month of life in agreement with the national immunization calendar. |
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E.4 | Principal exclusion criteria |
1) Participation in another clinical trial in the 4 weeks preceding the first trial vaccination.
2) Planned participation in another clinical trial during the present trial period.
3) Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy within the preceding 3 months, or long-term systemic corticosteroid therapy.
4) 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.
5) Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
6) Blood or blood-derived products received since birth that might interfere with the assessment of the immune response.
7) Any vaccination before trial vaccination (except Hep B and BCG given at birth).
8) Any planned vaccination until one month after the last trial vaccination (except the study vaccines, rotavirus and pneumococcal conjugated vaccines and for pandemic influenza vaccination, which may be received at least two weeks before each study vaccine dose).
9) Documented history of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b or Hep B infection(s) (confirmed either clinically, serologically or microbiologically).
10) Previous vaccination against pertussis, tetanus, diphtheria, poliomyelitis, or Haemophilus influenzae type b infections.
11) Known personal or maternal history of Human Immunodeficiency Virus (HIV), hepatitis B (HBsAg) or hepatitis C seropositivity.
12) Laboratory-confirmed or clinical suspicion of coagulopathy, thrombocytopenia or a bleeding disorder preceding inclusion contraindicating intra-muscular (IM) vaccination.
13) History of seizures or encephalopathy.
14) Febrile illness (temperature ≥38.0°C) or moderate or severe acute illness/infection, on the day of inclusion, according to the Investigator judgment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following serological endpoints will be assessed 1 month after the third dose of the primary series (V06, D140) for the lot-to-lot consistency and non-inferiority analyses:
- Antibody (Ab) titers for Hep B.
Seroprotection rates for D, T, Hep B, PRP, and polio with the following endpoints:
- Anti-D and anti-T Ab titers > or =0.01 IU/mL.
- Anti-Hep B Ab titers > or =10 mIU/mL.
- Anti-PRP Ab titers > or =0.15 µg/mL.
- Anti-polio 1, 2, and 3 Ab titers > or =8 (1/dil).
Seroresponse rates for anti-PT and anti-FHA with the following endpoints:
- Response to pertussis (PT, FHA) antigens defined as anti-PT or anti-FHA > or =Lower Limit of Quantitation (LLOQ) in initially seronegative subjects, or at least persistence (post-titer > or = pre titer) of the antibody titer in initially seropositive subjects (titer > or =LLOQ). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The above serological endpoints will be assessed 1 month after the third dose of the primary series (V06, D140) for the lot-to-lot consistency and non-inferiority analyses |
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E.5.2 | Secondary end point(s) |
Immunogenicity:
Endpoints for the immune response (descriptive) will include:
- Ab titers for D, PT, FHA, Hep B and rotavirus valences at V01.
- Ab titers above a cut-off (V01):
- Anti-D Ab titers > or =0.01 IU/mL and > or =0.1 IU/mL
- Anti-PT Ab titers > or =LLOQ
- Anti-FHA Ab titers > or =LLOQ
- Anti-Hep B Ab titers > or =10 mIU/mL and > or =100 mIU/mL
- Anti-rotavirus (Anti-RV) IgA > or =20 U/mL (in a subset of subjects only).
- Ab titers for Rotarix™ valence at V04.
- Ab titers above a cut-off (V04):
- Anti-RV IgA > or =20 U/mL (in a subset of subjects only).
- Ab titers for each valence at V06 except Rotarix™.
- Ab titers above a cut-off (V06):
- Anti-D antibody titers > or =0.1 IU/mL and > or =1.0 IU/mL.
- Anti-T antibody titers > or =0.1 IU/mL and > or =1.0 IU/mL.
- Anti-Hep B Ab titers > or =100 mIU/mL.
- Anti-PRP Ab titers > or =1.0 µg/mL.
- Anti-PT Ab titers > or =4 EU/mL
- Anti-FHA Ab titers > or =4 EU/mL
- Anti-pneumococcal serotype 4, 6B, 9V, 14, 18C, 19F and 23F titers > or =0.35 µg/mL (in a subset of subjects only).
- Ab individual titer ratios for anti-D and Hep B (V06/V01).
- Ab individual titer ratios for anti-PT and anti-FHA (V06/V01).
- Ab individual titers ratios for anti-rotavirus (V04/V01).
- Seroconversion for anti-RV IgA defined as anti-RV IgA > or =20 U/mL, in subject seronegative at pre-dose1 (V04/V01).
- Seroconversion for anti PT and anti FHA, defined as anti PT and anti FHA > or =four-fold Ab titers increase from V01 to V06
Safety:
- Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), duration, severity, and relationship to vaccination for any unsolicited systemic adverse events reported in the 30 minutes after each vaccination.
- Occurrence, time to onset, number of days of occurrence, and severity for solicited (prelisted in the subject diary and electronic case report form [eCRF]) injection site and systemic reactions occurring up to 7 days after each vaccination.
- Occurrence, nature (MedDRA preferred term), time to onset, duration, severity, and relationship to vaccination (for systemic adverse events only) of unsolicited (spontaneously reported) adverse events up to 30 days after each vaccination.
- Occurrence of SAEs throughout the trial (including the 6 months follow up period).
Effect of prophylactic antipyretics use :
- Ab titers for each valences of DTaP IPV-Hep B-PRP-T vaccine group only
- Ab titers above a cut-off (V02) for:
- Anti-D and anti-T antibody titers > or = 0.01, > or = 0.1 IU/mL and > or = 1.0 IU/mL
- Anti-Hep B Ab titers > or = 10 and > or = 100 mIU/mL
- Anti-PRP Ab titers > or = 0.15 and > or = 1.0 µg/mL
- Anti-poliovirus 1, 2, and 3 Ab titers > or = 8 (1/dil)
- Anti-PT Ab titers > or =4 EU/mL
- Anti-FHA Ab titers > or =4 EU/mL
Seroresponse rates for anti-PT and anti-FHA with the following endpoints:
- Response to pertussis (PT, FHA) antigens defined as anti-PT or anti-FHA > or =LLOQ in initially seronegative subjects, or at least persistence (post-titer > or = pre titer) of the Ab titer in initially seropositive subjects (titer > or =LLOQ). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A blood sample of approximately 4 mL will be taken at 2 months of age (BL1 - V01),
a 4-mL blood sample at 5 months of age (BL2 - V04) in a subset of subjects, and a 5-mL blood sample at 7 months of age (BL3 - V06).
There will be a total duration of 10 months for each subject (including a 6-month safety follow-up after the last injection). |
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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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 4 |
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 | Yes |
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 | 3 |