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 |
To assess the immunogenicity of Adacel (SP306) when administered as a single dose in Japanese adolescents. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of Adacel (SP306) when administered as a single dose in Japanese adolescents. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Aged 11 or 12 years and considered health on the day of inclusion
2. Informed consent form and assent form signed and dated by the parent(s) / legal representative and the subject respectively
3. Completed childhood vaccination against diphtheria, pertussis and tetanus (ie, received 4 doses of Japanese-produced DTaP vaccine), confirmed by checking immunization records and have not yet undergone additional DT vaccination
4. Able to attend all scheduled visits and to comply with all trial procedures
5. For female subjects, either pre-menarchal, or post-menarchal with a negative urine pregnancy test |
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E.4 | Principal exclusion criteria |
1. Any conditions or diseases which, in the opinion of the investigator
- would pose a health risk to the subject
- or might interfere with the ability to participate fully in the study
- or might interfere with evaluation of the vaccine
- or would otherwise make participation inappropriate according to the investigator’s clinical judgment
2. History of diphtheria, tetanus, pertussis, confirmed either clinically, serologically, or microbiologically
3. Known systemic hypersensitivity to any of the vaccine components or history of a life threatening reaction to a vaccine containing the same substances of the study vaccine
4. Vaccination in the last 5 years against tetanus, diphtheria, and/or pertussis
5. Known or suspected congenital immunodeficiency, or current / previous acquired immunodeficiency, or current / previous receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or current /
previous (within the last 6 months) systemic corticosteroid therapy
6. Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial inclusion
7. Planned participation in another clinical trial during the present trial period
8. Receipt of blood or blood–derived products in the past 3 months, that might interfere with assessment of the immune response
9. Receipt of any vaccine within the 4 weeks preceding the trial vaccination, except for influenza vaccination, which may be received at least 2 weeks before the study vaccine
10. Planned receipt of any vaccine during the trial period
11. Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or Human Immunodeficiency Virus (HIV) infection
12. At high risk for diphtheria, tetanus or pertussis infection during the trial
13. Known pregnancy, or a positive urine pregnancy test
14. Currently breastfeeding a child
15. Known thrombocytopenia, contraindicating IM vaccination, or a history of thrombocytopenia
16. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination
17. History of acute disseminated encephalomyelitis, encephalopathy, Guillain-Barré Syndrome (GBS), or autoimmune disease
18. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
19. Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
20. Identified as an employee of an Investigator, a study center, a study-affiliated vendor, or the Sponsor, with direct or indirect involvement in the proposed study or other studies under the direction of that Investigator or study center; or indentified as a spouse or child (whether natural or adopted) of such an employee
Temporary contraindications
A prospective subject should not be included in the study until the following conditions and/or symptoms are resolved:
• Febrile illness (temperature ≥37.5°C)
• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination
• Antipyretics/analgesics/non steroidal anti-inflammatory drugs (NSAIDs) (considered as a single category) have been administered within 4 hours prior to vaccination.
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E.5 End points |
E.5.1 | Primary end point(s) |
Diphtheria and tetanus
• For diphtheria and tetanus, proportion of subjects at 28 days (window, 28-35 days) post-vaccination with antitoxin
concentrations ≥0.1 IU/mL.
• For diphtheria and tetanus, proportion of subjects with booster responses based on antitoxin concentration rises between pre-vaccination and 28 days (window, 28-35 days) postvaccination specimens.
- A diphtheria booster response is defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a
subjects with a pre-vaccination antitoxin concentration ≤ 2.56 IU/mL or a ≥ 2-fold rise in a subject with a prevaccination antitoxin concentration > 2.56 IU/mL
- A tetanus booster response is defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.7 IU/mL or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration > 2.7 IU/mL
Pertussis
• For PT and FHA, proportion of subjects with booster responses based on antibody concentration rises between pre-vaccination and 28 days (window, 28-35 days) post-vaccination specimens.
The criteria for demonstrating these booster responses are as follows:
- Subjects whose pre-vaccination antibody concentrations are less than the lower limit of quantitation (LLOQ) will
demonstrate the booster response if they have post-vaccination levels ≥ 4xLLOQ
- Subjects whose pre-vaccination antibody concentrations are ≥ LLOQ but < 4xLLOQ will demonstrate the booster
response if they have a 4-fold rise (ie, post-/prevaccination ≥ 4)
- Subjects whose pre-vaccination antibody concentrations are ≥ 4xLLOQ will demonstrate the booster response if
they have a 2-fold rise (ie, post-/pre-vaccination ≥ 2) (The LLOQs of the pertussis antibody assays as performed at the Sanofi Pasteur laboratory of Global Clinical Immunology in Swiftwater, Pennsylvania, USA, are 4 EU/mL for antibody to PT and 3 EU/mL for antibody to FHA.) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Between Pre-Vaccination and 28 days: for pertussis, diphtheria and tetanus antibody concentration.
Post-Vaccination at 28 days (window, 28-35 days): for diphtheria and tetanus antibody concentration. |
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E.5.2 | Secondary end point(s) |
• Occurrence, intensity, and relationship to vaccination of any unsolicited systemic AEs reported within 30 minutes after vaccination.
• Occurrence, time to onset, number of days of occurrence and intensity of solicited injection-site and systemic reactions (terms prelisted in the subject’s diary card and case report form [CRF]) occurring from Day 0 to Day 7 after vaccination.
• Occurrence, nature (MedDRA preferred term), maximum intensity (for non-serious AEs only), and relationship to
vaccination (for systemic AEs only), of unsolicited AEs up to 28 days after vaccination.
• Occurrence, nature (MedDRA preferred term), relationship to vaccination, seriousness, and outcome of SAEs occurring for the entire duration of each subject’s involvement in the study. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Vaccination:
Day 0: 30 minutes after vaccination.
Post-Vaccination:
Day 0 through Day7, Day 28 and throughout the trial period. |
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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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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 days | 61 |