E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active immunization against tetanus, diphtheria and pertussis |
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E.1.1.1 | Medical condition in easily understood language |
Protection against tetanus, diphtheria and pertussis |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054129 |
E.1.2 | Term | Diphtheria 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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10069577 |
E.1.2 | Term | Pertussis 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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054131 |
E.1.2 | Term | Tetanus 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 |
Immunogenicity
• To describe seroprotection rates against tetanus and diphtheria in subjects randomized to receive either Adacel or Boostrix vaccine.
• To describe pre- and post-vaccination tetanus, diphtheria, and pertussis geometric mean antibody concentrations (GMCs) in subjects randomized to receive either Adacel or Boostrix vaccine.
• To describe booster response rates against tetanus, diphtheria, and pertussis in subjects randomized to receive either Adacel or Boostrix vaccine.
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E.2.2 | Secondary objectives of the trial |
Safety
•To describe the rates of AEs immediately post-vaccination, and the rates of unsolicited AEs and SAEs following vaccination with Adacel or Boostrix vaccine from Visit 1 through Visit 2.
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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) Subject is 11 to < 13 years of age at the time of vaccination.
2) Received exactly 5 doses of pertussis vaccine at < 7 years of age.
3) Informed consent and assent forms have been signed and dated.
4) Subject is able to attend all scheduled visits and to comply with all trial procedures.
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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) Subject is pregnant, or lactating, or of child bearing potential without using an effective method of contraception or not practicing abstinence for at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination.
2) Any condition that, in the opinion of the Investigator, would pose a health risk to the participant or interfere with the evaluation of the vaccine.
3) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
4) Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks) within the past 3 months).
5) Known or suspected receipt of any whole-cell pertussis-containing vaccine.
6) A personal history of physician-diagnosed or laboratory-confirmed pertussis disease within the last 2 years.
7) A previous severe reaction to pertussis, diphtheria or tetanus vaccine including immediate anaphylaxis, encephalopathy within 7 days, or seizure within 3 days of receiving the vaccine.
8) Receipt of immune globulins, blood or blood-derived products in the past 3 months.
9) Suspected or known 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.
10) Receipt of any vaccine within 30 days before receiving study vaccine, or plans to receive another vaccine before the 2nd visit; except that influenza vaccine may have been received between 30 and 15 days (but no less than 15 days) before receiving study vaccine.
11) Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the first study vaccination or during the course of the study, at the discretion of the Sponsor.
12) Seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C, as reported by the subject's parent/guardian.
13) Laboratory-confirmed thrombocytopenia, which may be a contraindication for IM vaccination, at the discretion of the Investigator.
14) Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for IM vaccination, at the discretion of the Investigator.
15) Personal history of Guillain-Barré syndrome.
16) Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of vaccination. (A prospective subject should not be enrolled in the study until the condition has resolved or the febrile event has subsided.)
17) Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
18) Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
19) Current alcohol or drug use that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures.
Note: Subjects enrolled into this study will not be prohibited from donating blood for non-interventional studies.
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity
Tetanus and Diphtheria:
• Frequencies and proportions of pre- and post-vaccination tetanus and diphtheria antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL among subjects in each vaccine group.
• Pre- and post-vaccination GMCs of antibody to tetanus and diphtheria among subjects in each vaccine group.
• Booster response rates to tetanus and diphtheria based on antibody rises pre- to post-vaccination among subjects in each vaccine group.
• For Adacel recipients, booster response is defined as a four-fold increase in pre- to post-vaccination antibody concentrations for subjects with a pre-vaccination concentration ≤ 2.56 IU/mL for diphtheria and ≤ 2.7 IU/mL for tetanus, and defined as a two-fold increase for subjects with a pre-vaccination concentration > 2.56 IU/mL for diphtheria and > 2.7 IU/mL for tetanus.
• For Boostrix recipients, booster response is defined as a post-vaccination titer > 4 times the lower limit of quantitation (LLOQ) for subjects with a pre-vaccination titer < LLOQ, a post-vaccination titer > 4 times the pre-vaccination titer for subjects with a pre-vaccination titer between LLOQ and 4xLLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer > 4xLLOQ.
• Reverse cumulative distribution curves (RCDCs) for each vaccine group.
Pertussis:
• Pre- and post-vaccination GMCs of antibody to PT, FHA, PRN, and FIM among subjects in each vaccine group.
• Booster response rates to PT, FHA, PRN, and FIM pre- to post-vaccination among subjects in each vaccine group.
• For Adacel recipients, booster response is defined as a four-fold increase in pre- to post-vaccination antibody concentrations for subjects with a pre-vaccination concentration ≤ 93 EU/mL for PT, ≤ 170 EU/mL for FHA, ≤ 115 EU mL for PRN, or ≤ 285 EU/mL for FIM, and defined as a two-fold increase for subjects with a pre-vaccination concentration > 93 EU/mL for PT, >170 EU/mL for FHA, >115 EU/mL for PRN, or > 285 EU/mL for FIM.
• For Boostrix recipients, booster response is defined as a post-vaccination titer > 4 times the LLOQ for subjects with a pre-vaccination titer < LLOQ, a post-vaccination titer > 4 times the pre-vaccination titer for subjects with a pre-vaccination titer between LLOQ and 4xLLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer > 4xLLOQ.
• RCDCs for each vaccine group.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pre-and Post-Vaccination: for pertussis, diphtheria and tetanus antibody concentrations, GMCs of antibodies and booster response rates.
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E.5.2 | Secondary end point(s) |
1) Occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), duration, intensity, and relationship to vaccination of adverse events (AEs) reported in the 15 minutes after vaccination.
2) Occurrence, nature (MedDRA preferred term), time to onset, duration, intensity, action taken, relationship to vaccination (for systemic AEs only), and whether the event led to early termination from the study, of unsolicited AEs from Visit 1 to Visit 2.
3) Occurrence, nature (MedDRA preferred term), time to onset, duration, seriousness criteria, relationship to vaccination, outcome, and whether the SAE led to early termination from the study, of serious adverse events from Visit 1 to Visit 2.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Vaccination:
Visit 1(Day 0): 15 minutes after vaccination.
Post-Vaccination:
Visit 1 to Visit 2 (approximately 28 days after 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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
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 |
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 months | 4 |