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

Tetanus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439165
• Other study ID #: Td537
• Secondary ID: U1111-1117-7012
• Status: Completed
• Phase: Phase 4
• Start date: November 2011
• Est. completion date: February 2017

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1330
• Est. completion date: February 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diphtheria
• Pertussis
• Tetanus
• Whooping Cough

Intervention

Biological:
• Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine
0.5 mL, Intramuscular
• Tetanus and Diphtheria Toxoids Adsorbed For Adult Use
0.5 mL, Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 Adult — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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