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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00489970
First received: June 21, 2007
Last updated: May 26, 2016
Last verified: May 2016
  Purpose

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).


Condition Intervention Phase
Acellular Pertussis
Tetanus
Diphtheria
Procedure: Taking of blood samples
Biological: Boostrix
Biological: Adacel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Persistence Study of GSK Biologicals' Tdap Vaccine (776423), 1, 3, 5 and 9 Years Following Administration as a Single Dose in NCT00346073 Study and to Evaluate the Immunogenicity and Safety of Boostrix as a Second Dose of Tdap, When Administered at Year 9

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Number of Subjects With Anti-tetanus (Anti-T) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-T cut-off was defined as greater than or equal to 0.1 IU/mL (ELISA).

  • Number of Subjects With Anti-tetanus (Anti-T) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-D cut-off was defined as greater than or equal to 0.1 international units per mililiter (IU/mL) determined with Enzyme-linked Immunosorbent Assay (ELISA) or VERO.


Secondary Outcome Measures:
  • Number of Subjects With Anti-pertussis Toxoid (PT) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    The cut-off for anti-PT concentrations was defined as equal to or greater than 5 ELISA units per mililiter (EL.U/mL).

  • Number of Subjects With Anti-filamentous Hemagglutinin (FHA) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    The cut-off for anti-FHA concentrations was defined as equal to or greater than 5 EL.U/mL.

  • Number of Subjects With Anti-pertactin (PRN) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    The cut-off for anti-PRN concentrations was defined as equal to or greater than 5 EL.U/mL.

  • Anti-D Antibody Concentration [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-D antibody concentration is expressed as geometric mean concentration (GMC) in IU/mL.

  • Anti-T Antibody Concentration [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-T antibody concentration is expressed as GMC in IU/mL.

  • Anti-PT Antibody Concentration [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-PT antibody concentration is expressed as GMC in EL.U/mL.

  • Anti-FHA Antibody Concentration [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-FHA antibody concentration is expressed as GMC in EL.U/mL.

  • Anti-PRN Antibody Concentration [ Time Frame: 1, 3 and 5 years following vaccination ] [ Designated as safety issue: No ]
    Anti-PRN antibody concentration is expressed as GMC in EL.U/mL.

  • Number of Subjects With Anti-pertussis Toxoid (PT) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Number of Subjects With Anti-filamentous Hemagglutinin (FHA) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Number of Subjects With Anti-pertactin (PRN) Antibody Concentrations Equal to or Above Protocol Specified Cut-off [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Anti-D Antibody Concentration [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Anti-T Antibody Concentration [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Anti-PT Antibody Concentration [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Anti-FHA Antibody Concentration [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]
  • Anti-PRN Antibody Concentration [ Time Frame: 9 years following vaccination ] [ Designated as safety issue: No ]

Enrollment: 1592
Study Start Date: June 2007
Study Completion Date: March 2016
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Boostrix Group
Subjects received in the primary study Subjects who had received Boostrix vaccine in study NCT00346073 and will receive a second dose of Boostrix vaccine in this study at Year 9.
Procedure: Taking of blood samples
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.
Biological: Boostrix
A single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study.
Active Comparator: Adacel Group
Subjects who had received Sanofi Pasteurs' Adacel™ vaccine in study NCT00346073 and will receive a second dose of Boostrix in this study at Year 9.
Procedure: Taking of blood samples
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.
Biological: Boostrix
A single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study.
Biological: Adacel
A single dose of Adacel was administered in the primary study (NCT00346073). No treatment was given in this study.
Active Comparator: Control group
Subjects in this group will receive the first dose of Tdap vaccine (Boostrix) in this study at Year 9.
Biological: Boostrix
A single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study.

Detailed Description:

Subjects were previously vaccinated with either Boostrix or a control Tdap vaccine (Sanofi Pasteurs' Adacel) in study NCT00346073. Only subjects who were part of the primary study will be invited to participate in this study. All subjects will receive a single dose of Boostrix at Visit 6 (Day 0) and subjects will be observed till Visit 7 (Day 30) for safety in terms of solicited adverse events (during 4 days post vaccination), unsolicited adverse events (during 31 days post vaccination) and serious adverse event (during the trial period). A blood sample will be collected from all subjects before vaccination (Visit 6) and one month after vaccination (Visit 7) for antibodies estimation.

This summary has been updated following Protocol amendment 1 dated 09 November 2010, amendment 2 dated 18 February 2014, and amendment 3 dated 10 December 2014. The protocol was amended first due to the following reasons:

  1. The maximum window period allowed for the return of subjects for the Year 5 and Year 10 follow-up visits (Visit 5 and Visit 6) was extended from ± 5 weeks to ± 8 weeks.
  2. The contact details for reporting of SAEs were clarified.
  3. Text pertaining to the reporting of spontaneous abortion was removed from the protocol.
  4. The number of attempts to contact subjects who did not return for scheduled persistence visits was clarified.

The main purpose of protocol amendment 2 is to evaluate the immunogenicity and safety of Boostrix as a second dose of Tdap vaccine when administered 8 years after an initial dose of Tdap. The Year 10 time point for evaluation of persistence has been cancelled because it is no longer feasible to conduct after a second dose of Tdap vaccine has been administered at Year 8.

The purpose of amendment 3 is to add co-primary objective to demonstrate that the immune response elicited by a second dose of Tdap vaccine, Boostrix (Boostrix group and Adacel group) is non-inferior to the immune response elicited by a first dose of Tdap vaccine (Control group), with respect to booster response against diphtheria, tetanus and pertussis (PT, FHA and PRN) antigens, one month following vaccination according to CBER's input. Accordingly, the study start has been pushed to Year 9 and this is reflected throughout the document.

  Eligibility

Ages Eligible for Study:   28 Years to 73 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

• 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.

Healthy subjects as established by medical history and clinical examination before entering into the study.

  • Female subjects of non-childbearing potential may be enrolled in the study.

    • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
  • Female subjects of child bearing potential may be enrolled in the study, if the subject

    • has practiced adequate contraception for 30 days prior to vaccination, and
    • has a negative pregnancy test on the day of vaccination, and
    • has agreed to continue adequate contraception for 1 month after completion of the vaccine dose

Exclusion Criteria:

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.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • Acute disease and/or fever at the time of enrolment.

    • Fever is defined as temperature ≥ 100.4°F by any route. The preferred route for recording temperature in this study will be oral.
    • Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
  • Administration of immunoglobulins and/or any blood products within three months preceding the dose of study vaccine or planned administration during the study period, 31 days (Day 0-30).

Administration of any tetanus or diphtheria containing vaccine or any registered or investigational vaccine utilizing a diphtheria toxoid or tetanus toxoid carrier within 5 years prior to the administration of Boostrix vaccine in this study.

  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions during the 31 day (Day 0-30) follow-up period post-vaccination.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489970

  Show 37 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00489970     History of Changes
Other Study ID Numbers: 110080  110082  110084  110086 
Study First Received: June 21, 2007
Results First Received: July 15, 2010
Last Updated: May 26, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Persistence
immunogenicity

Additional relevant MeSH terms:
Diphtheria
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 30, 2016