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] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 | 20.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 | 20.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe the safety profile after each and all doses of the study vaccine |
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E.2.2 | Secondary objectives of the trial |
• To demonstrate the non-inferiority of the immune response to all antigens induced by the study vaccine in Vietnamese infants one month after the third dose in a 3 dose Primary Series (2, 3 and 4 MoA) with the immune response to all antigens induced by the same study vaccine outside Vietnam (Cohort 1) • To evaluate the immunogenicity of the study vaccine one month after the 3-dose Primary Series (Cohort 1) • To describe the persistence of all antibodies (Abs) before receipt of the booster vaccination (Cohort 1) • To evaluate the immunogenicity of the study vaccine one month after the booster (Cohort 1)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged 61 to 91 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) ICF has been signed and dated by the parent(s) or other legally acceptable representative(s) (and by an independent witness if required by local regulations) 4) Subject and parent(s)/legally acceptable representative(s) were able to attend all scheduled visits and to comply with all trial procedures 5) Have received one dose of Hep B vaccine at birth or within 1 week after birth (documented according to the national recommendations)
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E.4 | Principal exclusion criteria |
1) Participation in the 4 weeks preceding the first trial vaccination 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 or planned receipt of any other vaccine within the period from 8 days before to 8 days after each subsequent trial vaccination except for BCG vaccination (any administration of oral polio vaccine [OPV] in the context of OPV-National Immunisation Days [NIDs] does not fall within the scope of this exclusion criterion) 3) Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B (except the dose of Hep B vaccine given at birth or within 1 week after birth) diseases or Haemophilus influenzae type b infection with either the trial vaccine or another vaccine (any administration of OPV in the context of OPV-NIDs does not fall within the scope of this exclusion criterion) 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 Haemophilus influenzae type b infections (confirmed either clinically, serologically or microbiologically) 7) Known personal or maternal history of Human Immunodeficiency Virus (HIV) or hepatitis C seropositivity 8) Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances 9) Known thrombocytopenia, as reported by the parent(s)/legally acceptable representative(s) 10) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination 11) History of seizures 12) In an emergency setting, or hospitalized involuntarily 13) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion 14) 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. 15) Identified as a natural or adopted child of the Investigator, relatives or employee with direct involvement in the proposed study
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Occurrence of all unsolicited systemic AEs reported in the 30 minutes after each and all vaccination(s). 2) Occurrence of solicited (prelisted in the subject’s DC and CRF) injection site and systemic reactions following each and all vaccination(s). 3) Occurrence of unsolicited AEs following each and all vaccination(s). 4) Occurrence of SAEs throughout the Primary Series period and booster period. In addition, all related SAEs, unrelated deaths and life-threatening SAEs were collected between D90 and D425.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 30 minutes after each and all vaccination(s) 2) D0-D7 following each and all vaccination(s) 3) Through 30 days following each and all vaccination(s) 4) All SAEs throughout the Primary Series trial period (from D0 to D90) and throughout the booster trial period (D425 to D455). In addition, all related SAEs, unrelated deaths and life-threatening SAEs are to be collected between D90 and D425.
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E.5.2 | Secondary end point(s) |
At baseline, before the first dose of study vaccine (D0, at approximately 2 months of age [MoA]): • Anti-PT and anti-FHA Ab concentrations ≥ Lower Limit of Quantitation (LLOQ) and ≥ 4 x LLOQ • Anti-PT and anti-FHA individual Ab concentrations One month after the third dose of study vaccine (D90, at approximately 5 MoA): • Anti-D Ab concentrations ≥ 0.01 and ≥ 0.1 IU/milliliter (mL) International Units (IU)/mL • Anti-T Ab concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL • Anti-PRP Ab concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL • Anti-poliovirus 1, 2, and 3 Ab titers ≥ 8 (1/dilution [dil]) • Vaccine response for pertussis toxoid (PT) and FHA antigens defined as post third dose anti-PT and anti-FHA Ab concentrations ≥ 4 x LLOQ if pre-vaccination concentration is < 4 x LLOQ or ≥ pre-vaccination concentration if pre-vaccination concentrations ≥ 4 x LLOQ • ≥ 4-fold* increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-dose 1 to one month post-dose 3 • Individual Ab concentration ratios for anti-PT and FHA (post-Dose 3/pre-Dose 1) • Anti-Hep B Ab concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL • Individual Ab concentrations/titers: all Abs * ≥ 4-fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-dose 1 to one month post-dose 3 corresponds to seroconversion. Booster vaccination: Before the booster dose of study vaccine (D425, at 16 to 17 MoA): • Individual Ab concentrations/titers: all Abs • Anti-PT and anti-FHA Ab concentrations ≥ LLOQ and ≥ 4 x LLOQ • Anti-D Ab concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL • Anti-T Ab concentrations ≥ 0.01 IU/mL and ≥ 0.1 IU/mL • Anti-polyribosyl ribitol phosphate (PRP) Ab concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL • Anti-poliovirus 1, 2, and 3 Ab titers ≥ 8 (1/dil) • Anti-Hep B Ab concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL One month after the booster dose of study vaccine (D455, at 17 to 18 MoA): • Anti-D Ab concentrations ≥ 0.01 IU/mL, ≥ 0.1 IU/mL, and 1.0 IU/mL • Anti-T Ab concentrations ≥ 0.01 IU/mL, ≥ 0.1 IU/mL, and 1.0 IU/mL • Anti-polyribosyl ribitol phosphate (PRP) Ab concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL • Anti-poliovirus 1, 2, and 3 Ab titers ≥ 8 (1/dil) • Vaccine response for pertussis toxoid (PT) and filamentous hemagglutinin (FHA) antigens defined as post-fourth dose anti-PT and anti-FHA Ab concentrations ≥ 4 x LLOQ, if pre-vaccination concentration < 4 x LLOQ or ≥ pre-vaccination concentration, if pre-vaccination concentrations ≥ 4 x LLOQ • Booster response for PT and FHA antigens: ≥ 4-fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-Booster to one month post Booster if pre-Booster Ab concentrations < 4x LLOQ; or ≥ 2 fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-Booster to one month post-Booster if pre Booster Ab concentrations ≥ 4x LLOQ • ≥ 4-fold* increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-dose 4 to one month post-dose 4 • Ab individual concentration ratios for all antigens (one month post Dose 4/pre-Dose 4) • Anti-Hep B Ab concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL • Individual Ab concentrations/titers: all Abs * ≥ 4-fold increase in anti-PT and anti-FHA Ab concentrations (EU/mL) from pre-dose 4to one month post-dose 4 corresponds to seroconversion.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline before the first dose of study vaccine (D0), before the booster dose of study vaccine (D425), and one month after the booster dose (D455) |
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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.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
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 | 15 |