| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy infants 46 to 74 days of age (both inclusive) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Healthy infants 46 to 74 days of age (both inclusive) |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054187 |
| E.1.2 | Term | Polio immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10069543 |
| E.1.2 | Term | Hemophilus influenzae type b immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10069593 |
| E.1.2 | Term | Pertussis immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054181 |
| E.1.2 | Term | Hepatitis B immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054180 |
| E.1.2 | Term | Diphtheria immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054183 |
| E.1.2 | Term | Tetanus immunization |
| E.1.2 | System Organ Class | 100000004865 |
|
| 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 |
PRIMARY SERIES:
- To demonstrate that the concomitant administration of the hexavalent vaccine given at 2, 3 and 4 months of age with a meningococcal serogroup C conjugate (MenC) vaccine given at 2 and 4 months of age is non inferior to the administration of the hexavalent vaccine without a MenC vaccine concomitantly in term of seroprotection rate for hepatitis B one month after the third dose of the hexavalent vaccine.
- To demonstrate that the concomitant administration of a MenC vaccine given at 2 and 4 months of age with the hexavalent vaccine given at 2, 3 and 4 months of age induces an acceptable response for MenC in term of seroprotection rate (SPR) one month after the second dose of MenC.
BOOSTER:
To describe the immunogenicity of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate vaccine either co-administered at 12 months of age or given separately. |
|
| E.2.2 | Secondary objectives of the trial |
PRIMARY SERIES:
Immunogenicity:
-To describe the antibody response to all the hexavalent vaccine antigens one month after the third dose of the hexavalent vaccine when given concomitantly or not to MenC vaccine.
-To describe the antibody response to MenC vaccine when a MenC vaccine is given concomitantly with the hexavalent vaccine, one month after the first and the second dose of MenC vaccine.
Safety:
-To describe the safety profile of the hexavalent vaccine after each and any injection when given concomitantly or not with a MenC vaccine.
BOOSTER:
Immunogenicity:
To describe the antibody (Ab) persistence at 12 months of age for the hexavalent valences following a 3-dose primary vaccination at 2, 3 and 4 months of age (prior to administration of a booster dose)
Safety:
To describe the safety of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
PRIMARY SERIES:
1. Healthy infant 46 to 74 days of age (both inclusive)
2. Born at full term of pregnancy (≥37 weeks) and/or with a birth weight≥2.5 kg
3. Informed consent signed by the subject's parent(s) or legal representative
4. Subject's parent(s) or legal representative able to comply with the study procedures
such as adherence to study visits and completion of the diary cards
5. Covered by health insurance
BOOSTER:
1. Infant who received 3 doses of the hexavalent vaccine in the Primary series
2. Healthy infant from 12 months of age
3. Informed consent signed by the subject's parent(s) or legal representative |
|
| E.4 | Principal exclusion criteria |
PRIMARY SERIES:
1. Participation at the time of study enrolment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
2. Receipt of any vaccine in the 4 weeks preceding each study vaccination or planned receipt of a vaccine in the 4 weeks following each study vaccine administration
3. Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal, rotavirus infection
4. Know or suspected congenital, hereditary or acquired immunodeficiency or other immunosuppressive or immunodeficiency condition
5. History of seizures or encephalopathy
6. Known thrombocytopenia, as reported by the subject's parent or legal representative
7. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
8. Chronic illness that, in the opinion of the investigators, is at a stage where it might interfere with trial conduct or completion
9. Known or suspected hypersensitivity to any of the study vaccines' active substance or excipients or history of a life-threatening reaction to a vaccine(s) containing the same substances as the study vaccines
10. Contraindication to any of the study vaccines as per their Summary of Product Characteristics
11. Known personal or maternal history of hepatitis B (HBs Ag) or hepatitis C seropositivity
12. History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup C infection
13. Receipt of immune globulin, blood or blood-derived products since birth
14. Receipt of immunosuppressive therapy or other immune-modifying drugs, such as anticancer chemotherapy or radiation therapy since birth
15. Receipt of systemic corticosteroid therapy for more than 14 consecutive days since birth
16. Identified as a natural or adopted child of the investigator or employee with direct involvement in the current study.
BOOSTER:
1. Prior (in the last 4 weeks), current or planned participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure during the entire duration of the Booster vaccination
2. Receipt of a flu vaccine in the 2 weeks preceding vaccination at Visit 5 or receipt of any vaccine in the 4 weeks preceding vaccination at Visit 5 or planned receipt of a vaccine in the 4 weeks following vaccination at Visit 5
3. Previous booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal infections with either the trial vaccine or another vaccine
4. History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup A, C, W or Y infection(s) confirmed either clinically, serologically, or microbiologically
5. Known or suspected hypersensitivity to any of the active substance or excipients or trace residuals of the hexavalent vaccine or the meningococcal group ACWY conjugate vaccine, to any pertussis vaccine, history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines
6. Contraindication to the hexavalent vaccine or the meningococcal group ACWY conjugate vaccine, as per their Summary of Product Characteristics
7. Receipt of immune globulin, blood or blood-derived products in the last 3 months
8. Receipt of immunosuppressive therapy or other immune-modifying drugs, such as anti-cancer chemotherapy or radiation therapy in the last 3 months
9. Receipt of systemic corticosteroid therapy for more than 14 consecutive days in the last 3 months
10. Known or suspected congenital, hereditary or acquired immunodeficiency or other immunosuppressive or immunodeficiency condition
11. History of seizures or encephalopathy; uncontrolled neurologic disorder or uncontrolled epilepsy
12. Known thrombocytopenia, as reported by the subject's parent(s) or legal representative
13. Bleeding disorder, or receipt of anticoagulants in the last 3 weeks, contraindicating intramuscular injection
14. Chronic illness that, in the opinion of the investigators, is at a stage where it might interfere with trial conduct or completion |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
PRIMARY SERIES
Immunogenicity:
- Proportion of subjects with an anti-HBs concentration ≥10 mIU/mL
- Proportion of subjects with an anti-MenC titre ≥1:8 dil
BOOSTER:
Immunogenicity of hexavalent vaccine:
-Proportion of subjects with an anti-D concentration ≥0.1 IU/mL
-Proportion of subjects with an anti-D concentration ≥1.0 IU/mL
-Proportion of subjects with an anti-T concentration ≥0.1 IU/mL
-Proportion of subjects with an anti-T concentration ≥1.0 IU/mL
-Proportion of subjects with an anti-IPV1 titres ≥1:8 dil
-Proportion of subjects with an anti-IPV2 titres ≥1:8 dil
-Proportion of subjects with an anti-IPV3 titres ≥1:8 dil
-Proportion of subjects with an anti-HBs concentration ≥10 mIU/mL
-Proportion of subjects with an anti-HBs concentration ≥100 mIU/mL
-Proportion of subjects with an anti-PRP concentration ≥0.15 μg/mL
-Proportion of subjects with an anti-PRP concentration ≥1.0 μg/mL
-Booster response for pertussis antigens (PT and FHA) defined as follows:
- Post-booster Ab concentrations ≥4-fold rise if pre-booster Ab concentrations <4x LLOQ
- Post-booster Ab concentrations ≥2-fold rise if pre-booster Ab concentrations ≥4x LLOQ
-Anti-PT ≥4-fold Ab concentrations increase from pre- (Visit 5) to post-booster (Visit 6)
-Anti-FHA ≥4-fold Ab concentrations increase from pre- (Visit 5) to post-booster (Visit 6)
-Anti-D GMC
-Anti-T GMC
-Anti-IPV1 GMTs
-Anti-IPV2 GMTs
-Anti-IPV3 GMTs
-Anti-HBs GMC
-Anti-PRP GMC
-Anti-PT GMCs
-Anti-FHA GMCs
Immunogenicity of MenACWY vaccine:
-Proportion of subjects with an anti-MenA titre ≥1:8 dil
-Proportion of subjects with an anti-MenC titre ≥1:8 dil
-Proportion of subjects with an anti-MenW-135 titre ≥1:8 dil
-Proportion of subjects with an anti-MenY titre ≥1:8 dil
-Anti-MenA GMTs
-Anti-MenC GMTs
-Anti-MenW-135 GMTs
-Anti-MenY GMTs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
PRIMARY SERIES:
One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine.
BOOSTER:
One month after administration of hexavalent and/or MenACWY (at 13 months of age) |
|
| E.5.2 | Secondary end point(s) |
PRIMARY SERIES:
Immunogenicity:
- Anti-HBs geometric mean concentrations (GMC)
- Proportion of subjects with an anti-PRP concentration ≥0.15 µg/mL
- Anti-PRP GMC
- Proportion of subjects with an anti-diphtheria (D) concentration ≥0.1 IU/mL
- Proportion of subjects with an anti-D concentration ≥0.01 IU/mL
- Anti-D geometric mean concentration (GMC)
- Proportion of subjects with an anti-tetanus (T) concentration ≥0.1 IU/mL
- Proportion of subjects with an anti-T concentration ≥0.01 IU/mL
- Anti-T GMC
- Proportion of subjects with an anti-inactivated poliovirus (IPV)1 titre ≥1:8 dil
- Proportion of subjects with an anti-IPV2 titre ≥1:8 dil
- Proportion of subjects with an anti-IPV3 titre ≥1:8 dil
- Anti-IPV1, anti-IPV2 and anti-IPV3 GMTs
- Proportion of subjects with an anti-PT vaccine response
- Proportion of subjects with anti-FHA vaccine response
- Anti-PT and anti-FHA GMCs
- Anti-PT and anti-FHA GMCRs
- Anti-PT and anti-FHA 4-fold increase
- Proportion of subjects with an anti-MenC titre ≥1:8 dil
- Proportion of subjects with an anti-MenC titre ≥1:128 dil
- Anti-MenC GMT
Safety:
- Incidence of solicited injection-sites reactions and solicited systemic adverse event.
- Incidence of unsolicited injection-site reactions, unsolicited systemic adverse events and all serious adverse events.
BOOSTER:
Immunogenicity, hexavalent vaccine:
-Proportion of subjects with an anti-D concentration ≥0.01 IU/mL
-Proportion of subjects with an anti-D concentration ≥0.1 IU/mL
-Proportion of subjects with an anti-T concentration ≥0.01 IU/mL
-Proportion of subjects with an anti-T concentration ≥0.1 IU/mL
-Proportion of subjects with an anti-IPV1 titre ≥1:8 dil
-Proportion of subjects with an anti-IPV2 titre ≥1:8 dil
-Proportion of subjects with an anti-IPV3 titre ≥1:8 dil
-Proportion of subjects with an anti-HBs concentration ≥10 mIU/mL
-Proportion of subjects with an anti-HBs concentration ≥100 mIU/mL
-Proportion of subjects with an anti-PRP concentration ≥0.15 μg/mL
-Proportion of subjects with an anti-PRP concentration ≥1.0 μg/mL
-Anti-PT and anti-FHA ≥ LLOQ, 2x LLOQ
-Anti-PT and anti-FHA ≥ LLOQ, 2x LLOQ
-Anti-D GMC
-Anti-T GMC
-Anti-IPV1 GMTs
-Anti-IPV2 GMTs
-Anti-IPV3 GMTs
-Anti-HBs GMC
-Anti-PRP GMC
-Anti-PT GMCs
-Anti-FHA GMCs
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PRIMARY SERIES:
Immunogenicity:
One month after dose 3 of Hexavalent vaccine
Proportion of subjects with an anti-MenC titre ≥1:8 dil: one month after dose 1 of MenC vaccines
Proportion of subjects with an anti-MenC titre ≥1:128 dil and Anti-MenC GMT: one month after dose 1 and one month after dose 2 of MenC vaccine.
Safety:
From Day 0 to Day 30 after each vaccination
BOOSTER:
Immunogenicity: Prior to administration of the hexavalent booster at 12 months of age
Safety: From Day 0 to Day 30 after vaccination |
|
| 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 | 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 | Yes |
| 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 | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
| The end of data collection including availability of final serology results |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 10 |
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