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

• ClinicalTrials.gov Identifier: NCT02089347
• Recruitment Status: Completed
• First Posted: March 17, 2014
• Results First Posted: October 8, 2015
• Last Update Posted: May 30, 2017
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Tetanus; Diphtheria; Pertussis	Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed; Biological: Diphtheria and Tetanus toxoids adsorbed	Phase 3

Detailed Description:

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 534 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: March 2014
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: SP306 Group; Participants randomized to receive SP306 vaccine intramuscularly	Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed; 0.5 mL, intramuscularly.; Other Names: Adacel; SP306 (in Japan)
Active Comparator: DT Group; Participants randomized to receive DT vaccine subcutaneously	Biological: Diphtheria and Tetanus toxoids adsorbed; 0.1 mL, Subcutaneously; Other Name: DT vaccine

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Diphtheria and Tetanus Post-vaccination Booster Response Following Vaccination With Either SP306 or DT [ Time Frame: Day 28 post-vaccination ]

   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

2. Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Post-booster Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 28 post-vaccination ]

   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

3. Percentage of Participants With Pertussis Booster Response Following Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 28 post-vaccination ]

   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.

Secondary Outcome Measures :

1. Percentage of Participation With Seroprotection to Diphtheria and Tetanus Antigens Before Vaccination With Either SP306 or DT Vaccine [ Time Frame: Pre-vaccination (Day 0) ]

   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.

2. Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]

   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.

3. Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
4. Percentage of Participants With Pertussis (Pertactin and Fimbriae Types 2 and 3) Booster Response Following Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 28 post-vaccination ]

   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.

5. Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method
6. Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine [ Time Frame: Day 0 up to Day 7 post-vaccination ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 11 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Japan

Aichi, Japan, 451 8511

Chiba, Japan, 299 4503

Fukui, Japan, 910 0833

Fukui, Japan, 918 8205

Gunma, Japan, 372 0817

Hyogo, Japan, 655 0017

Ibaraki, Japan, 312 0057

Kagoshima, Japan, 890 0034

Kanagawa, Japan, 223 0051

Nagano, Japan, 381 0025

Okayama, Japan, 701 0205

Okayama, Japan, 712 8064

Osaka, Japan, 574 0046

Shizuoka, Japan, 420 8623

Shizuoka, Japan, 426 0067

Tokyo, Japan, 146 0023

Tokyo, Japan, 146 0095

Tokyo, Japan, 167 0052

Tokyo, Japan, 183 0042

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info 

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02089347
• Other Study ID Numbers: Td536 (EFC12579); U1111-1124-7550 ( Other Identifier: WHO )
• First Posted: March 17, 2014
• Results First Posted: October 8, 2015
• Last Update Posted: May 30, 2017
• Last Verified: April 2017

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Tetanus; Diphtheria; Pertussis; TdaP vaccine; DT vaccine

Additional relevant MeSH terms:

Whooping Cough; Tetanus; Diphtheria; Tetany; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Respiratory Tract Infections; Infection; Respiratory Tract Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Hypocalcemia; Calcium Metabolism Disorders; Metabolic Diseases; Corynebacterium Infections; Actinomycetales Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs