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] - Immune System Diseases [C20] |
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 |
|
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 |
|
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 non-inferiority of SP306 versus DT (DT Biken 0.1 mL) vaccine in terms of diphtheria and tetanus booster response rate (proportion of subjects with booster responses) and seroprotection rate (percentage of subjects with antitoxin concentrations ≥0.1 IU/mL) at 28 days (window 28-35 days) after one injection in Japanese adolescents 11-12 years of age.
To evaluate the immune response of SP306 against the pertussis antigens PT and FHA in terms of booster response rate (proportion of subjects with booster responses) at 28 days (window 28-35 days) after one injection in Japanese adolescents 11-12 years of age. |
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E.2.2 | Secondary objectives of the trial |
IMMUNOGENICITY
To further evaluate the immune response of the study vaccines against diphtheria, tetanus and pertussis antigens.
SAFETY
To assess the safety of the study vaccines after one injection in Japanese adolescents 11-12 years of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
An individual had to fulfill all of the following criteria in order to be eligible for trial
enrollment:
I 01. Aged 11 or 12 years and considered health on the day of inclusion
I 02. Informed consent form and assent form signed and dated by the parent(s) / legal representative(s) and the subject respectively
I 03. Completed childhood vaccination against diphtheria, pertussis and tetanus (i.e., received 4 doses of Japanese produced DTaP vaccine), confirmed by checking immunization records and have not yet undergone additional DT vaccination
I 04. Able to attend all scheduled visits and to comply with all trial procedures
I 05. For female subjects, either pre-menarchal or post-menarchal, with a negative urine pregnancy test |
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E.4 | Principal exclusion criteria |
An individual fulfilling any of the following criteria was excluded from trial enrollment:
E01. 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
E02. History of diphtheria, tetanus, pertussis, confirmed either clinically, serologically, or microbiologically
E03. Suspected or known 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
E04. Vaccination in the last 5 years against tetanus, diphtheria, and/or pertussis
E05. 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
E06. Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial inclusion
E07. Planned participation in another clinical trial during the present trial period
E08. Receipt of blood or blood–derived products in the past 3 months, that might interfere with assessment of the immune response
E09. 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
E10. Planned receipt of any vaccine during the trial period
E11. Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or Human Immunodeficiency Virus (HIV) infection
E12. At high risk for diphtheria, tetanus or pertussis infection during the trial
E13. Known pregnancy, or a positive urine pregnancy test
E14. Currently breastfeeding a child
E15. Known thrombocytopenia or history of thrombocytopenia
E16. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding
E17. History of acute disseminated encephalomyelitis, encephalopathy, Guillain-Barré Syndrome (GBS), or autoimmune disease
E18. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
E19. Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
E20. 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 identified as a spouse or child (whether natural or adopted) of such an employee |
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E.5 End points |
E.5.1 | Primary end point(s) |
Diphtheria and tetanus
Proportion of subjects with booster responses based on diphtheria and tetanus antitoxin concentration rises between pre-vaccination and 28 days (window, 28-35 days) post-vaccination specimens.
- A diphtheria booster response was defined as a ≥4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤2.56 IU/mL or a ≥2-fold rise in a subject with a pre-vaccination antitoxin concentration >2.56 IU/mL
- A tetanus booster response was 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
Proportion of subjects at 28 days (window, 28-35 days) post-vaccination with diphtheria and tetanus antitoxin concentrations ≥0.1 IU/mL (seroprotective
level)
Pertussis
Proportion of subjects with booster responses against pertussis antigens (PT and FHA) based on antibody concentration rises between pre-vaccination and 28 days (window, 28-35 days) post-vaccination specimens.
- For subjects whose pre-vaccination antibody concentrations were less than the lower limit of quantitation (LLOQ) , a booster response was demonstrated if they had post-vaccination levels ≥4xLLOQ
- For subjects whose pre-vaccination antibody concentrations were ≥LLOQ but <4xLLOQ, a booster response was demonstrated if they had a 4-fold rise (i.e., post-/pre-vaccination ≥4)
- For subjects whose pre-vaccination antibody concentrations were ≥4xLLOQ, a booster response was demonstrated if they had a 2-fold rise (i.e., post-/pre-vaccination ≥2) (The LLOQs of the pertussis antibody assays as performed at GCI were 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 |
Refer to primary end point information above for timepoints of evaluation. |
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E.5.2 | Secondary end point(s) |
Immunogenicity
Diphtheria and tetanus
• Proportion of subjects with pre-vaccination diphtheria and tetanus antitoxin concentrations ≥0.1 IU/mL
• Proportion of subjects with pre-vaccination and 28 days (window, 28-35 days) post-vaccination diphtheria and tetanus antitoxin concentrations ≥0.01, and ≥1.0 IU/mL
• Diphtheria and tetanus antitoxin geometric mean concentrations (GMC) at pre-vaccination and 28 days (window, 28-35 days) post-vaccination
• Diphtheria and tetanus antitoxin geometric mean fold rises (GMFR) between pre- and post-vaccination blood samples
Pertussis
Proportion of subjects with booster responses against pertussis antigens (PRN and FIM) based on antibody concentration rise between pre-vaccination and
28 days (window, 28-35 days) post-vaccination specimens.
- For subjects whose pre-vaccination antibody concentrations were less than LLOQ, a booster response was demonstrated if they had post-vaccination levels ≥4xLLOQ
- For subjects whose pre-vaccination antibody concentrations were ≥LLOQ but <4xLLOQ, a booster response was demonstrated if they had a 4-fold rise (i.e., post-/pre-vaccination ≥4)
- For subjects whose pre-vaccination antibody concentrations were ≥4xLLOQ, a booster response was demonstrated if they had a 2-fold rise (i.e., post-/pre-vaccination ≥2) (The LLOQs of the pertussis antibody assays as performed at GCI were 4 EU/mL for antibody to both PRN and FIM.)
• Pertussis antibody (PT, FHA, PRN and FIM) GMC pre-vaccination and 28 days (window, 28-35 days) post-vaccination
• Pertussis antibody (PT, FHA, PRN and FIM) GMFR between pre- and post-vaccination blood samples
• Pertussis antibody (PT and FHA) measured by ELISA kit manufactured by DENKA SEIKEN Co., Ltd. in Japan:
- Proportion of sero-positive – defined as antibody concentration ≥10 EU/mL – at pre-vaccination and 28 days (window, 28-35 days) post-vaccination
- GMC at pre-vaccination and 28 days (window, 28-35 days) post-vaccination
- GMFR between pre- and post-vaccination blood samples
- Safety
• Occurrence, intensity, and relationship to vaccination of any unsolicited systemic AEs reported within the 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 electronic case report form [eCRF]) 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 |
Refer to secondary end point information above for timepoints of evaluation. |
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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) | 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 | Yes |
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 | No |
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 |
E.8.9.2 | In all countries concerned by the trial days | 5 |