Persistence Study of GSK Biologicals' Tdap Vaccine 1, 3, 5 and 9 Years Following Administration as an Initial Single Dose in Healthy Young Adults and to Evaluate the Immunogenicity and Safety of Boostrix as a Second Dose of Tdap, When Administered at Year 9

NCT00489970 | Completed Phase 3 Results

• 4 other identifiers: 110080110082110084110086
• Study Type: interventional
• Target: 1,954
• Locations: 1 country
• Sites: 37

Brief Summary

The purpose of this study is to evaluate the persistence of antibodies against all the vaccine antigens 1, 3, 5 and 9 years after an initial vaccination with Tdap, and also to assess immunogenicity and safety of another dose of Boostrix, administered in this study. This protocol posting deals with objectives and outcome measures of the extension phase. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00346073).

Conditions

Acellular Pertussis; Tetanus; Diphtheria

Keywords

Persistence; immunogenicity

Outcome Measures

Primary Outcomes (13)

• Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Greater Than or Equal to (≥) Protocol Specified Cut-off

  Anti-D cut-off was defined as ≥ 0.1 International Units per milliliter (IU/mL) determined with Enzyme-linked Immunosorbent Assay (ELISA)

  At year 1 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-D cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA

  At year 3 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-D cut-off was defined as ≥ 0.1IU/mL as assessed by ELISA.

  At year 5 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-D cut-off was defined as ≥ to 0.1IU/mL as assessed by ELISA.

  At Year 9, one month before the booster vaccination.

• Number of Subjects With Anti-tetanus (Anti-T) Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.

  At year 1 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.

  At year 3 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.

  At year 5 after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off

  Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.

  At Year 9, one month before the booster vaccination.

• Number of Subjects With Anti-D and Anti-T Concentrations ≥ 0.1 IU/mL and 1 IU/mL

  Number of subjects with anti-D and anti-T concentrations ≥ 0.1 IU/mL and 1 IU/mL were tabulated

  At Year 9, one month after the booster vaccination.

• Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations

  Anti-PT, anti-FHA and anti-PRN antibody concentrations were measured by ELISA, tabulated as GMCs and expressed in IU/mL.

  At Year 9, one month before booster vaccination

• Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations

  Anti-PT, anti-FHA and anti-PRN antibody concentrations were measured by ELISA, tabulated as GMCs and expressed in IU/mL.

  At Year 9, one month after the booster vaccination

• Booster Response to D and T Antigens

  A booster response was defined as: for initially seronegative subjects (S-) (pre-vaccination concentration below cut-off: \< 0.1 IU/mL) antibody concentrations at least four times the cut-off (post vaccination concentration ≥ 0.4 IU/mL); for initially seropositive subjects (S+) (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least four times the pre-vaccination concentration; Total = subjects either seropositive or seronegative.

  At Year 9, one month after the booster vaccination.

• Booster Response to PT, FHA and PRN Antigens

  Booster response was defined as: for subjects with pre-vaccination antibody concentration \< 5 EL.U/mL (S-): antibody concentration ≥ 20 EL.U/mL; for subjects with pre-vaccination antibody concentration ≥ 5 EL.U/mL and \< 20 EL.U/mL (S+, \<4\*cut-off): antibody concentration at least four times the pre-vaccination concentration; for subjects with pre-vaccination antibody concentration ≥ 20 EL.U/mL (S+, ≥4\*cut-off): antibody concentration at least two times the pre-vaccination concentration; Total = subjects either seropositive or seronegative

  At Year 9, one month after the booster vaccination.

Secondary Outcomes (24)

• Number of Subjects With Anti-pertussis Toxoid (PT) Antibody Concentrations Equal to or Above Protocol Specified Cut-off

  At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-PT Antibody Concentrations Equal to or Above Protocol Specified Cut-off

  At Year 9, one month before(pre booster) and after the booster vaccination(post booster)

• Number of Subjects With Anti-FHA Antibody Concentrations Equal to or Above Protocol Specified Cut-off

  At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)

• Number of Subjects With Anti-FHA Antibody Concentrations Equal to or Above Protocol Specified Cut-off

  At Year 9, one month before(pre booster) and after the booster vaccination(post booster)

• Number of Subjects With Anti-PRN Antibody Concentrations Equal to or Above Protocol Specified Cut-off

  At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)

Study Arms (3)

Boostrix Group

EXPERIMENTAL

Subjects received in the primary study (NCT00346073) a single dose of Boostrix vaccine \[Tdap\](GSK776423) intramuscularly in the deltoid region of the non-dominant upper arm and in this study at Year 9 received a second dose of Boostrix vaccine \[Tdap\](GSK776423).

Procedure: Taking of blood samples; Biological: Boostrix

Adacel Group

ACTIVE COMPARATOR

Subjects received in the primary study (NCT00346073) a single dose of Adacel vaccine intramuscularly in the deltoid region of the non-dominant upper arm and in this study at Year 9 received a dose of Boostrix vaccine \[Tdap\](GSK776423).

Procedure: Taking of blood samples; Biological: Boostrix; Biological: Adacel

Control group

ACTIVE COMPARATOR

Subjects received the first dose of Boostrix vaccine \[Tdap\](GSK776423) in this study at Year 9.

Biological: Boostrix

Interventions

Taking of blood samples PROCEDURE

No treatment is planned to be given in this study. Blood samples will be collected at the following time points: 1 year, 3 years, 5 years and 9 years after the dose of vaccination.

Adacel Group; Boostrix Group

Boostrix BIOLOGICAL

A single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study.

Adacel Group; Boostrix Group; Control group

Adacel BIOLOGICAL

A single dose of Adacel was administered in the primary study (NCT00346073). No treatment was given in this study.

Adacel Group

Eligibility Criteria

• Age: 28 Years - 73 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persistence follow-up phase up to Year 9 time point:
• The following criteria are applicable to subjects who refuse vaccination at Year 8 time point:
• All subjects who received study vaccination (Boostrix or Adacel) in study NCT00346073 will be considered eligible to participate in this study.
• Written informed consent must be obtained from the subject prior to each study time point.
• Vaccination phase at Year 9 applicable for subjects in Boostrix and Adacel groups only:
• The following criterion is applicable to subjects willing to consent to vaccination at Year 9 time point in the Boostrix and Adacel groups:
• All subjects who received study vaccination (Boostrix or Adacel) in study NCT00346073 will be considered eligible to participate in this study.
• Vaccination phase at Year 9 applicable for subjects in the Control group only:
• The following criterion is applicable to subjects willing to consent to vaccination at Year 9 time point in the Control group only:
• Subjects within the age range of 28-73 years will be considered eligible to participate in this study in the Control group.
• Vaccination phase at Year 9 applicable for ALL subjects (Control, Boostrix and Adacel groups):
• The following criteria are applicable to subjects willing to consent to vaccination at Year 9 time point in the Boostrix, Adacel and Control groups:
• All subjects must satisfy the following criteria at study entry at Year 9 time point:
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written informed consent obtained from the subject for vaccination at Year 9 time point.

You may not qualify if:

• The following criteria should be checked at the time of Year 9 vaccination time point. If any criteria is applicable, the subject must not be vaccinated in the study:
• For subjects in Boostrix and Adacel groups:
• Administration of Tdap vaccine since the last dose received in the study NCT00346073.
• For subjects in the Control group:
• Administration of Tdap (Boostrix or Adacel) vaccine at any time prior to the administration of Boostrix vaccine in this study.
• For ALL subjects (Control, Boostrix and Adacel groups):
• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period, 31 days (Day 0-30).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to Visit 6 (pre-vacc). Inhaled and topical steroids are allowed.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of vaccine, with the exception of inactivated Influenza vaccine which is allowed throughout the study period, 31 days (Day 0-30).
• \-- Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
• Hypersensitivity to latex.
• History of diphtheria, tetanus or pertussis diseases.
• Severe allergic reaction (e.g. anaphylaxis) after previous administration of any tetanus toxoid, diphtheria toxoid, or pertussis-antigen containing vaccines, or any component of Boostrix.
• History of any neurological disorders or seizures.
• Encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) of unknown etiology occurring within seven days following previous vaccination with pertussis-containing vaccine.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (37)

GSK Investigational Site

Huntsville, Alabama, 35802, United States

Location

GSK Investigational Site

Chandler, Arizona, 85224, United States

Location

GSK Investigational Site

Mesa, Arizona, 85203, United States

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GSK Investigational Site

Mesa, Arizona, 85213, United States

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GSK Investigational Site

Phoenix, Arizona, 85014, United States

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GSK Investigational Site

Tempe, Arizona, 85283, United States

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GSK Investigational Site

Little Rock, Arkansas, 72205, United States

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GSK Investigational Site

San Diego, California, 92103-6204, United States

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GSK Investigational Site

San Diego, California, 92108, United States

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GSK Investigational Site

Colorado Springs, Colorado, 80909, United States

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GSK Investigational Site

Pueblo, Colorado, 81001, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20006, United States

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GSK Investigational Site

Melbourne, Florida, 32935, United States

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GSK Investigational Site

Miami, Florida, 33143, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33024, United States

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GSK Investigational Site

Boise, Idaho, 83704, United States

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GSK Investigational Site

Peoria, Illinois, 61602, United States

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GSK Investigational Site

South Bend, Indiana, 46601, United States

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GSK Investigational Site

Bardstown, Kentucky, 40004, United States

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GSK Investigational Site

Richland, Michigan, 49083, United States

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GSK Investigational Site

St Louis, Missouri, 63141, United States

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GSK Investigational Site

North Platte, Nebraska, 69101, United States

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GSK Investigational Site

Raleigh, North Carolina, 27609, United States

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GSK Investigational Site

Tabor City, North Carolina, 28463, United States

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GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

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GSK Investigational Site

Oklahoma City, Oklahoma, 73112, United States

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GSK Investigational Site

Erie, Pennsylvania, 16505, United States

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GSK Investigational Site

Grove City, Pennsylvania, 16127, United States

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GSK Investigational Site

Johnstown, Pennsylvania, 15904, United States

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GSK Investigational Site

Pittsburgh, Pennsylvania, 15241, United States

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GSK Investigational Site

Charleston, South Carolina, 29412, United States

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GSK Investigational Site

Bristol, Tennessee, 37620, United States

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GSK Investigational Site

Houston, Texas, 77024, United States

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GSK Investigational Site

Salt Lake City, Utah, 84109, United States

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GSK Investigational Site

Salt Lake City, Utah, 84121, United States

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GSK Investigational Site

West Jordan, Utah, 84088, United States

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GSK Investigational Site

Norfolk, Virginia, 23507, United States

Location

Related Publications (2)

• Brandon D, Kimmel M, Kuriyakose SO, Kostanyan L, Mesaros N. Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults. Vaccine. 2018 Oct 8;36(42):6325-6333. doi: 10.1016/j.vaccine.2018.08.051. Epub 2018 Sep 7.

  PMID: 30197282 BACKGROUND

• Weston W, Messier M, Friedland LR, Wu X, Howe B. Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine. Vaccine. 2011 Nov 3;29(47):8483-6. doi: 10.1016/j.vaccine.2011.09.063. Epub 2011 Sep 25.

  PMID: 21945698 DERIVED

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.
• Redacted with child studies \& included

MeSH Terms

Conditions

Tetanus; Diphtheria

Interventions

Boostrix; adacel

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Corynebacterium Infections; Actinomycetales Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2007
• First Posted: June 22, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: March 1, 2016
• Last Updated: May 1, 2020
• Results First Posted: August 11, 2010

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (37)