Study of SP306 Given Intramuscularly Compared to DT Given Subcutaneously in Japanese Adolescents 11 - 12 Years Old

Study Overview
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Brief Summary
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The aim of the study is to generate additional safety and immunogenicity data to support the registration of the product in Japan. Primary objectives: To demonstrate the non-inferiority of SP306 versus DT (DT 0.1mL) 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. Secondary objectives: To further evaluate the immune response of the study vaccines against diphtheria, tetanus and pertussis antigens. To assess the safety of the study vaccines after one injection in Japanese adolescents 11-12 years of age.

Detailed Description
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Study participants will receive either a single dose of SP306 vaccine intramuscularly or a dose of DT vaccine subcutaneously. They will be monitored after vaccination for immediate adverse events (AEs) solicited injection site and systemic reactions and unsolicited AEs including serious adverse events throughout the study period, approximately 28 days (+7 days).

Official Title
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Immunogenicity and Safety of the Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (SP306) Given Intramuscularly Compared to Diphtheria and Tetanus Toxoids Adsorbed (DT) Given Subcutaneously in Japanese Adolescents 11 - 12 Years of Age

Conditions
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Tetanus, Diphtheria, Pertussis

Intervention / Treatment
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* Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed
* Biological: Diphtheria and Tetanus toxoids adsorbed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 11 or 12 years and considered healthy on the day of inclusion Informed consent form and assent form signed and dated by the parent(s) / legal representative(s) and the subject respectively 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 Able to attend all scheduled visits and to comply with all trial procedures For female subjects, either pre-menarchal, or post-menarchal with a negative urine pregnancy test. Exclusion Criteria: 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 History of diphtheria, tetanus, pertussis, confirmed either clinically, serologically, or microbiologically 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 Vaccination in the last 5 years against tetanus, diphtheria, and/or pertussis 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 Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the trial inclusion Planned participation in another clinical trial during the present trial period Receipt of blood or blood-derived products in the past 3 months, that might interfere with assessment of the immune response 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 Planned receipt of any vaccine during the trial period Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or Human Immunodeficiency Virus (HIV) infection At high risk for diphtheria, tetanus or pertussis infection during the trial Known pregnancy, or a positive urine pregnancy test Currently breastfeeding a child Known thrombocytopenia or history of thrombocytopenia Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion History of acute disseminated encephalomyelitis, encephalopathy, Guillain-Barré Syndrome (GBS), or autoimmune disease Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures 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.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SP306 Group<br>Participants randomized to receive SP306 vaccine intramuscularly | Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed<br>* 0.5 mL, intramuscularly.<br>* Other names: SP306 (in Japan);|
| Active Comparator: DT Group<br>Participants randomized to receive DT vaccine subcutaneously | Biological: Diphtheria and Tetanus toxoids adsorbed<br>* 0.1 mL, Subcutaneously<br>* Other names: DT vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Diphtheria and Tetanus Post-vaccination Booster Response Following Vaccination With Either SP306 or DT | 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 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. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method | Day 28 post-vaccination | 
| Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Post-booster Vaccination With Either SP306 or DT Vaccine | Seroprotection was defined as the proportion of subjects at 28 days post-vaccination with diphtheria and tetanus antitoxin concentration ≥0.1 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method | Day 28 post-vaccination | 
| Percentage of Participants With Pertussis Booster Response Following Vaccination With Either SP306 or DT Vaccine | Pertussis booster response was defined as a pre-vaccination antibody concentration less than the lower limit of quantitation (LLOQ) and a post vaccination level ≥ 4XLLOQ; or a pre-vaccination antibody concentration ≥ LLOQ but < 4XLLOQ and a 4-fold rise (i.e. post/pre-vaccination ≥ 4); or a pre-vaccination antibody concentrations ≥ 4XLLOQ and a 2-fold rise (i.e. post/pre-vaccination ≥2). Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method. | Day 28 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participation With Seroprotection to Diphtheria and Tetanus Antigens Before Vaccination With Either SP306 or DT Vaccine | Seroprotection was defined as the proportion of participants with pre-vaccination with diphtheria and tetanus antitoxin concentration ≥ 0.1 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method. | Pre-vaccination (Day 0) | 
| Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine | Seroprotection was defined as the proportion of participants with diphtheria and tetanus antitoxin concentration level ≥ 0.01 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine | Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Percentage of Participants With Pertussis (Pertactin and Fimbriae Types 2 and 3) Booster Response Following Vaccination With Either SP306 or DT Vaccine | Pertussis booster response was defined as a pre-vaccination antibody concentration less than the lower limit of quantitation (LLOQ) and a post-vaccination level ≥ 4XLLOQ; or a pre-vaccination antibody concentration ≥ LLOQ but < 4XLLOQ and a 4-fold rise (i.e. post/pre-vaccination ≥ 4); or a pre-vaccination antibody concentrations ≥ 4XLLOQ and a 2-fold rise (i.e. post/pre-vaccination ≥2). Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method. | Day 28 post-vaccination | 
| Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine | Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine | Solicited injection-site: Pain, Erythema, Swelling; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 injection-site: Pain Significant, prevents daily activity; Erythema and Swelling >100 mm. Grade 3 systemic reactions: Fever, >39˚C; Headache, Malaise, and Myalgia, Significant, prevents daily activity. | Day 0 up to Day 7 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tetanus, Diphtheria, Pertussis, TdaP vaccine, DT vaccine