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

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.

Study Overview

• Status: Completed
• Conditions: Pertussis; Whooping Cough; Tetanus; Diphtheria
• Intervention / Treatment: Biological: Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine; Biological: Tetanus and Diphtheria Toxoids Adsorbed For Adult Use

Detailed Description

Healthy adults < 65 years of age who received Adacel vaccine 10 years previously will be randomized to receive either Adacel or TENIVAC (Td Adsorbed) vaccine. They will be assessed for immunogenicity at baseline and post-vaccination. Safety data will be collected for 6 months following vaccination.

• Study Type: Interventional
• Enrollment (Actual): 1330
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • Harbour Grace, Newfoundland and Labrador, Canada, A0A2M0
    • St. John, Newfoundland and Labrador, Canada, A1B3V6
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
    • Little Rock, Arkansas, United States, 72205
  • California
    • San Diego, California, United States, 92108
  • Colorado
    • Boulder, Colorado, United States, 80304
  • Georgia
    • Marietta, Georgia, United States, 30062
    • Woodstock, Georgia, United States, 30189
  • Illinois
    • Peoria, Illinois, United States, 61602
  • Indiana
    • Mishawaka, Indiana, United States, 46545
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Maryland
    • Rockville, Maryland, United States, 20850
  • Massachusetts
    • Woburn, Massachusetts, United States, 01801
  • Missouri
    • Columbia, Missouri, United States, 65212
    • Saint Louis, Missouri, United States, 63104
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
  • New York
    • Brooklyn, New York, United States, 11201
    • Ithaca, New York, United States, 14850
    • Rochester, New York, United States, 14618
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
    • Winston-Salem, North Carolina, United States, 27103
  • Ohio
    • Cincinnati, Ohio, United States, 45229
    • Cleveland, Ohio, United States, 44121
  • Pennsylvania
    • Clairton, Pennsylvania, United States, 15025
    • Hershey, Pennsylvania, United States, 17033
    • Latrobe, Pennsylvania, United States, 15650
    • Pittsburgh, Pennsylvania, United States, 15224
  • Utah
    • Syracuse, Utah, United States, 84075
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
  • Washington
    • Vancouver, Washington, United States, 98686
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
    • Marshfield, Wisconsin, United States, 54449

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• 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.

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. 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).
• Known or suspected receipt of tetanus toxoid (T), tetanus and diphtheria toxoids (Td), or tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine since receipt of the qualifying dose of Adacel vaccine described in Inclusion Criterion #2.
• 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.
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular (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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adacel® Vaccine Group; Participants randomized to receive a repeat dose of Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine (Adacel®)	Biological: Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine; 0.5 mL, Intramuscular; Other Names: Adacel®
Active Comparator: Td Adsorbed Vaccine Group; 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; 0.5 mL, Intramuscular; Other Names: TENIVAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions	Injection site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection site reactions: Pain, Significant, prevents daily activity. Erythema and Swelling, >100 mm. Grade 3 Systemic reactions: Fever, ≥39°C or ≥102.1 F; Headache, Malaise, and Myalgia, Significant; prevents daily activity.	Day 0 up to Day 7 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Actual): April 28, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Diphtheria; Tetanus; whooping cough; Adacel vaccine
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Clostridium Infections; Corynebacterium Infections; Whooping Cough; Tetanus; Diphtheria
• Other Study ID Numbers: Td537; U1111-1117-7012 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org