Immunogenicity of Adacel® and BOOSTRIX® Vaccines in Adolescents

Phase 4

Completed

• Conditions: Whooping Cough; Tetanus; Pertussis; Diphtheria
• Interventions: Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (BOOSTRIX®); Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Adacel®)

• Registration Number: NCT01629589
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

The aim of this study is to describe immunogenicity of a single booster dose of Adacel vaccine versus Boostrix vaccine among approximately 420 adolescents 11 to \<13 years of age.

Primary objective:

* To describe seroprotection rates against tetanus and diphtheria in subjects randomized to receive either Adacel or Boostrix vaccine.

Observational objectives:

* 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.

* To describe the rates of adverse events (AEs) immediately post-vaccination, and the rates of unsolicited AEs and serious adverse events (SAEs) following vaccination with Adacel or Boostrix vaccine from Visit 1 through Visit 2.

Detailed Description

Participants will be randomized in a 1:1 ratio to receive either Adacel or Boostrix vaccine.

Subjects will be monitored for immediate reactions for 15 minutes post-vaccination. Unsolicited adverse events and serious adverse events will be collected from Visit 1 through Visit 2.

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-06-22
• Study First Submitted QC: 2012-06-25
• Study First Posted: 2012-06-27
• Primary Completion: 2013-03
• Study Completion: 2013-06
• Results First Submitted: 2013-08-16
• Results First Submitted QC: 2013-08-16
• Results First Posted: 2013-10-21
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-02
• Last Update Posted: 2016-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 423

Inclusion Criteria

• Subject is 11 to < 13 years of age at the time of vaccination
• Received exactly 5 doses of pertussis vaccine at < 7 years of age
• Informed consent and assent forms have been signed and dated
• Subject is able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria

• 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
• 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
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
• 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)
• Known or suspected receipt of any whole-cell pertussis-containing vaccine
• A personal history of physician-diagnosed or laboratory-confirmed pertussis disease within the last 2 years
• 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
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• 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
• 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
• 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
• Seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C, as reported by the subject's parent/guardian
• Laboratory-confirmed thrombocytopenia, which may be a contraindication for intramuscular (IM) vaccination, at the discretion of the Investigator
• 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
• Personal history of Guillain-Barré syndrome
• 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.)
• 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
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol or drug use that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Boostrix® Vaccine Group	Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (BOOSTRIX®)	Participants randomized to receive a single dose of Boostrix® vaccine
Adacel® Vaccine Group	Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Adacel®)	Participants randomized to receive a single dose of Adacel® vaccine

Primary Outcome Measures

Name	Time	Method
Number of Participants With Antibody Responses to Tetanus and Diphtheria Components Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Day 0 (pre-vaccination) to Day 28 (post-vaccination)	Tetanus antibody was assayed by Enzyme-linked immunosorbent assay (ELISA) and Diphtheria antibody by a toxin neutralization test. Antibody responses to tetanus and diphtheria components were defined as titers ≥0.1 IU/mL and ≥1.0 IU/mL

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Concentrations of the Pertussis Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Day 0 (pre-vaccination) to Day 28 post-vaccination	Pertussis antibodies Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN), and Fimbriae types 2 and 3 (FIM 2\&3) were assayed by Enzyme-linked immunosorbent assay (ELISA)
Number of Participants Reporting Immediate Unsolicited Adverse Events Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Up to 15 minutes post-vaccination	The 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 and systemic AEs.
Geometric Mean Concentrations of Tetanus and Diphtheria Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Day 0 (pre-vaccination) to Day 28 post-vaccination	Tetanus antibody was assayed by Enzyme-linked immunosorbent assay (ELISA) and Diphtheria antibody by a toxin neutralization test
Number of Participants With Booster Responses Against the Pertussis Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Day 28 post-vaccination	Adacel booster response defined as: a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with a pre vaccination concentration ≤93 ELISA Unit (EU)/mL for Pertussis toxoid (PT), ≤170 EU/mL for Filamentous hemagglutinin (FHA), ≤115 EU mL for pertactin (PRN), or ≤285 EU/mL for Fimbriae types 2 and 3 (FIM), and defined as a 2-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.; Boostrix booster response 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 4x LLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer ≥4x LLOQ.
Number of Participants With Booster Responses Against Tetanus and Diphtheria Antigens Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine	Day 28 post-vaccination	Adacel booster response defined as: a 4-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 2-fold increase for subjects with a pre-vaccination concentration \>2.56 IU/mL for diphtheria and \>2.7 IU/mL for tetanus.; Boostrix booster response 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 4x LLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer ≥4x LLOQ.