Safety and Immunogenicity in Adults of Revaccination With Adacel® Vaccine 10 Years After a Previous Dose

NCT01439165 | Completed Phase 4 Results

• 2 other identifiers: Td537U1111-1117-7012
• Study Type: interventional
• Target: 1,330
• Locations: 2 countries
• Sites: 33

Brief Summary

The purpose of this study is to describe the safety and immunogenicity of repeat administration of Adacel vaccine approximately 10 years following initial administration of the vaccine. Antibody levels prior to revaccination will also be used to characterize antibody persistence following initial vaccination 10 years earlier. Primary Objectives:

• To compare seroprotection rates against tetanus and diphtheria induced by Adacel vaccine to those induced by Td Adsorbed vaccine.
• To compare booster response rates against tetanus and diphtheria induced by Adacel vaccine to those induced by Td Adsorbed vaccine.
• To compare anti-pertussis geometric mean antibody concentrations (GMCs) induced by Adacel vaccine to the GMCs induced by Daptacel® vaccine given to infants. Secondary Objectives:
• To describe the rates of immediate reactions, solicited reactions, unsolicited adverse events (AEs), and serious adverse events (SAEs) following vaccination with Adacel or Td Adsorbed vaccine.
• To describe booster response rates for pertussis antigens following revaccination with Adacel vaccine.

Conditions

Tetanus; Diphtheria; Pertussis; Whooping Cough

Keywords

Adacel vaccine; Tetanus; Diphtheria; whooping cough

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Diphtheria and Tetanus Seroprotection

  Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. Seroprotection was defined as the following: Anti-Diphtheria and Anti-Tetanus ≥ 0.1 IU/mL.

  1 month post-booster vaccination

• Percentage of Participants With Diphtheria and Tetanus Booster Response

  Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. A booster response was defined as a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with pre-vaccination antibody concentrations ≤2.56 IU/mL for diphtheria and ≤ 2.7 IU/mL for tetanus. If the pre vaccination antibody concentrations were \> 2.56 IU/mL for diphtheria and \> 2.7 IU/mL for tetanus, then a 2-fold increase in response rate was defined as a booster response.

  1 month post-booster vaccination

• Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies

  Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin (FHA), Pertactin, Fimbriae types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Anti-pertussis GMCs further to Adacel vaccination was compared to an historical control group with Daptacel (NCT00255047 for pertussis toxoid and PMID 8538705 for FHA, Pertactin and Fimbriae) since Td Adsorbed Vaccine does not contain any pertussis antigens.

  1 month post-booster vaccination

• Percentage of Subjects With Pertussis Antigen Booster Response

  Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin \[FHA\], Pertactin, Fimbriae (types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Booster response is defined as a minimum rise in antibody concentration from pre- to post-vaccination. The minimum rise is at least 2 times if the pre-vaccination concentration is above the cutoff value, or at least 4 times if it is at or below the cutoff value. Anti-pertussis toxoid booster response rates further to Adacel vaccination was compared to an expected booster rates based on study Td506 (PMID 15933223) since Td Adsorbed Vaccine does not contain any pertussis antigens.

  1 month post-booster vaccination

Secondary Outcomes (1)

• Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions

  Day 0 up to Day 7 post-vaccination

Study Arms (2)

Adacel® Vaccine Group

EXPERIMENTAL

Participants randomized to receive a repeat dose of Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine (Adacel®)

Biological: Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine

Td Adsorbed Vaccine Group

ACTIVE COMPARATOR

Participants randomized to receive Subjects randomized to receive a Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (TENIVAC) vaccine.

Biological: Tetanus and Diphtheria Toxoids Adsorbed For Adult Use

Interventions

Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine BIOLOGICAL

0.5 mL, Intramuscular

Also known as: Adacel®

Adacel® Vaccine Group

Tetanus and Diphtheria Toxoids Adsorbed For Adult Use BIOLOGICAL

0.5 mL, Intramuscular

Also known as: TENIVAC

Td Adsorbed Vaccine Group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is ≥ 18 to \< 65 years of age at the time of vaccination.
• Received Adacel vaccine no less than 9 and no more than 11 years previously.
• Informed consent form has been signed and dated.
• Subject is able to attend all scheduled visits and to comply with all trial procedures.

You may not qualify if:

• 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. Females who are pre-menarche or post-menopausal for at least one year, or surgically sterile will not be excluded.
• 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).
• A personal history of physician-diagnosed or laboratory-confirmed pertussis disease within the last 10 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.
• Laboratory-confirmed thrombocytopenia, 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (33)

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Huntsville, Alabama, 35802, United States

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Jonesboro, Arkansas, 72401, United States

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Little Rock, Arkansas, 72205, United States

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San Diego, California, 92108, United States

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Boulder, Colorado, 80304, United States

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Marietta, Georgia, 30062, United States

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Woodstock, Georgia, 30189, United States

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Peoria, Illinois, 61602, United States

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Mishawaka, Indiana, 46545, United States

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Louisville, Kentucky, 40202, United States

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Rockville, Maryland, 20850, United States

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Woburn, Massachusetts, 01801, United States

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Columbia, Missouri, 65212, United States

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St Louis, Missouri, 63104, United States

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Albuquerque, New Mexico, 87108, United States

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Brooklyn, New York, 11201, United States

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Ithaca, New York, 14850, United States

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Rochester, New York, 14618, United States

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Raleigh, North Carolina, 27612, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45229, United States

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Cleveland, Ohio, 44121, United States

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Clairton, Pennsylvania, 15025, United States

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Hershey, Pennsylvania, 17033, United States

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Latrobe, Pennsylvania, 15650, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Syracuse, Utah, 84075, United States

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Virginia Beach, Virginia, 23456, United States

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Vancouver, Washington, 98686, United States

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Chippewa Falls, Wisconsin, 54729, United States

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Marshfield, Wisconsin, 54449, United States

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Harbour Grace, Newfoundland and Labrador, A0A2M0, Canada

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St. John's, Newfoundland and Labrador, A1B3V6, Canada

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Related Publications (2)

• Halperin SA, Donovan C, Marshall GS, Pool V, Decker MD, Johnson DR, Greenberg DP; Tdap Booster Investigators. Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose. J Pediatric Infect Dis Soc. 2019 May 11;8(2):105-114. doi: 10.1093/jpids/pix113.

  PMID: 29438562 RESULT

• Pool V, Tomovici A, Johnson DR, Greenberg DP, Decker MD. Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine in the USA. Vaccine. 2018 Apr 19;36(17):2282-2287. doi: 10.1016/j.vaccine.2018.03.029. Epub 2018 Mar 21.

  PMID: 29573876 DERIVED

MeSH Terms

Conditions

Tetanus; Diphtheria; Whooping Cough

Interventions

Tetanus Toxoid; Diphtheria Toxoid; Pertussis Vaccine; adacel; Diphtheria-Tetanus Vaccine

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Corynebacterium Infections; Actinomycetales Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines, Combined

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur Inc.

RegistryContactUs@sanofipasteur.com

Study Officials

• Medical Director

  Sanofi Pasteur Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: September 23, 2011
• Study Start: November 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2017
• Last Updated: April 28, 2022
• Results First Posted: October 9, 2017

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); US (31)