Acellular PertussisPhase 3NCT00489970
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
A Phase 3 study testing Taking of blood samples, Boostrix and Adacel in people with Acellular Pertussis and Tetanus, run by GlaxoSmithKline at 37 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 28 to 73 yearsHealthy volunteers can take part
- Conditions the study is for
- Acellular Pertussis, Tetanus, Diphtheria
- What is being tested?
- Taking of blood samples, Boostrix and Adacel
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,954 participants
- Where
- 37 sitesUnited States
- Study dates
- 1 Jun 2007to 1 Mar 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 73 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
Show all 22Show fewer
- 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
Who cannot join
- 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):
Show all 24Show fewer
- 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.
Trial locations and contacts
37 sites in 1 country.
37 sites in 1 country
United States37 sites
GSK Investigational Site
Bardstown, Kentucky, 40004
GSK Investigational Site
Boise, Idaho, 83704
GSK Investigational Site
Bristol, Tennessee, 37620
GSK Investigational Site
Chandler, Arizona, 85224
GSK Investigational Site
Charleston, South Carolina, 29412
GSK Investigational Site
Colorado Springs, Colorado, 80909
GSK Investigational Site
Erie, Pennsylvania, 16505
GSK Investigational Site
Grove City, Pennsylvania, 16127
GSK Investigational Site
Houston, Texas, 77024
GSK Investigational Site
Huntsville, Alabama, 35802
GSK Investigational Site
Johnstown, Pennsylvania, 15904
GSK Investigational Site
Little Rock, Arkansas, 72205
GSK Investigational Site
Melbourne, Florida, 32935
GSK Investigational Site
Mesa, Arizona, 85203
GSK Investigational Site
Mesa, Arizona, 85213
GSK Investigational Site
Miami, Florida, 33143
GSK Investigational Site
Norfolk, Virginia, 23507
GSK Investigational Site
North Platte, Nebraska, 69101
GSK Investigational Site
Oklahoma City, Oklahoma, 73112
GSK Investigational Site
Pembroke Pines, Florida, 33024
GSK Investigational Site
Peoria, Illinois, 61602
GSK Investigational Site
Phoenix, Arizona, 85014
GSK Investigational Site
Pittsburgh, Pennsylvania, 15241
GSK Investigational Site
Pueblo, Colorado, 81001
GSK Investigational Site
Raleigh, North Carolina, 27609
GSK Investigational Site
Richland, Michigan, 49083
GSK Investigational Site
Salt Lake City, Utah, 84109
GSK Investigational Site
Salt Lake City, Utah, 84121
GSK Investigational Site
San Diego, California, 92103-6204
GSK Investigational Site
San Diego, California, 92108
GSK Investigational Site
South Bend, Indiana, 46601
GSK Investigational Site
St Louis, Missouri, 63141
GSK Investigational Site
Tabor City, North Carolina, 28463
GSK Investigational Site
Tempe, Arizona, 85283
GSK Investigational Site
Washington D.C., District of Columbia, 20006
GSK Investigational Site
West Jordan, Utah, 84088
GSK Investigational Site
Winston-Salem, North Carolina, 27103
About this study
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
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).
Read the 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:
- 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.
- The contact details for reporting of SAEs were clarified.
- Text pertaining to the reporting of spontaneous abortion was removed from the protocol.
- 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.
- Conditions
- Acellular Pertussis, Tetanus, Diphtheria
- Being tested
- Taking of blood samples, Boostrix, Adacel
- Keywords
- Persistence, immunogenicity
- Medical subject headings
- Tetanus, Diphtheria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Taking of blood samplesProcedure or surgery
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.
BoostrixBiological
A single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study.
AdacelBiological
A single dose of Adacel was administered in the primary study (NCT00346073). No treatment was given in this study.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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. Receives: Biological: Boostrix |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
The cut-off for anti-PT concentrations was defined as ≥ 5 ELISA units per mililiter (EL.U/mL).
Measured: 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
The cut-off for anti-PT concentrations was defined as equal to or greater than 2.693 IU/mL.
Measured: 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
The cut-off for anti-FHA concentrations was defined as equal to or greater than 5 EL.U/mL.
Measured: 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
The cut-off for anti-FHA concentrations was defined as equal to or greater than 2.046 IU/mL
Measured: 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
The cut-off for anti-PRN concentrations was defined as equal to or greater than 5 EL.U/mL.
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Number of Subjects With Anti-PRN Antibody Concentrations Equal to or Above Protocol Specified Cut-off
The cut-off for anti-PRN concentrations was defined as equal to or greater than 2.187 IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-D Antibody Concentration
Anti-D antibody concentration is expressed as geometric mean concentration (GMC) in IU/mL.
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-D Antibody Concentration
Anti-D antibody concentration is expressed as GMC in IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-T Antibody Concentration
Anti-T antibody concentration is expressed as GMC in IU/mL.
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-T Antibody Concentration
Anti-T antibody concentration is expressed as GMC in IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-PT Antibody Concentration
Anti-PT antibody concentration is expressed as GMC in EL.U/mL.
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-PT Antibody Concentration
Anti-PT antibody concentration was expressed as GMC in IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-FHA Antibody Concentration
Anti-FHA antibody concentration is expressed as GMC in IU/mL
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-FHA Antibody Concentration
Anti-FHA antibody concentration was expressed as GMC in IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-PRN Antibody Concentration
Anti-PRN antibody concentration is expressed as GMC in IU/mL
Measured: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-PRN Antibody Concentration
Anti-PRN antibody concentration is expressed as GMC in IU/mL.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Alternative Booster Response to Anti-D and Anti-T Antigens
Alternative Booster response to D and T antigens is defined as: - For subjects with pre-booster antibody concentration below 0.1 IU/mL: antibody concentrations at least four times the 0.1IU/ML, one month after vaccination, and - For subjects with pre-booster antibody concentration ≥0.1 IU/mL and <1.0 IU/mL: antibody concentrations of at least four times the pre-booster antibody concentration, one month after vaccination. - For subjects with pre-booster antibody concentration ≥1.0 IU/mL and <6.0 IU/mL: antibody concentrations of at least two times the pre-booster antibody concentration, one month after vaccination. - Subjects with pre-booster antibody concentration ≥6.0 IU/mL are not evaluable for booster response. S- = Antibody concentration < 0.1 IU/mL S+ = Antibody concentration ≥ 0.1 IU/mL Total = subjects either seropositive or seronegative
Measured: At Year 9, one month after booster vaccination
Alternative Booster Responses to Anti-PT, Anti-FHA and Anti-PRN Antigens
Alternative Booster response to PT, FHA and PRN antigens is defined as: - For subjects with pre-booster antibody concentration below the assay cut off: antibody concentrations at least four times the assay cut off one month after vaccination, and - For subjects with pre-booster antibody concentration ≥ assay cut off and < 60 IU/mL: antibody concentration increase of at least 30 IU/mL from the pre-booster antibody concentration, one month after vaccination. - For subjects with pre-booster antibody concentration ≥ 60 IU/mL : at least 1.5 fold increase of antibody concentration from the pre-booster antibody concentration, one month after vaccination. S- = seronegative subjects (antibody concentration below assay cut off for anti-PT, anti-FHA, anti-PRN) S+ = seropositive subjects (antibody concentration below assay cut off for anti-PT, anti-FHA, anti-PRN) Total = subjects either seropositive or seronegative
Measured: At Year 9, one month after booster vaccination
Seroprotection Status for Anti-D Antibody Concentration
Seroprotection status for anti-D antibody concentration < 0.1 IU/mL were tested for neutralizing antibodies using a VERO-cell neutralization assay. Seroprotection rate is defined as the percentage of subjects with antibody concentrations greater than or equal (≥) the seroprotection cut-off value defined for that antibody.
Measured: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Year 9
Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities. Grade 3 redness and swelling was greater than 50 millimeters (mm)
Measured: During the 4-day (Days 0-3) post vaccination period.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms - Year 9
The solicited general symptoms assessed were Fatigue, Gastrointestinal symptoms (including nausea, vomiting, diarrhea and abdominal pain), Headache and Fever [defined as temperature of ≥100.4 degrees Fahrenheit (F) by any route]. Any = Occurrence of any general symptom regardless of its intensity grade or relationship to vaccination; Grade 3 Symptom = Symptom that prevented normal activity; Grade 3 Fever > 104.0 degrees F.
Measured: During the 4-day (Days 0-3) post vaccination period.
Number of Subjects With Any Large Injection Site Reaction - Year 9
Large injection site reaction = a swelling with a diameter > 100 mm, noticeable diffuse swelling or noticeable increase in limb circumference.
Measured: During the 4-day (Days 0-3) follow-up period after vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AEs) - Year 9
An unsolicited AE covers any untoward medical oc-currence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Measured: During the 31-day (Days 0-30) post-vaccination period.
Number of Subjects With Serious Adverse Events (SAEs) - Year 9
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: During the 31-day (Days 0-30) post-vaccination period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2007 (estimated)
- Study start1 Jun 2007
- Primary completion1 Sep 2011
- Study completion1 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acellular PertussisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,954 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489970
- Sponsor's protocol ID
- 110080
- Other IDs
- 110082, 110084, 110086
- Status last verified
- Apr 2020
- First submitted
- 21 Jun 2007
- Last updated
- 1 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Publications
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.
PubMed 30197282Weston 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.
PubMed 21945698
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00489970
- Acronym / sponsor ID
- 110080
- Conditions
- Acellular Pertussis, Tetanus, Diphtheria
- Keywords
- Persistence, immunogenicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,954 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jun 2007 (actual)
- Primary completion
- 1 Sep 2011 (actual)
- Study completion
- 1 Mar 2016 (actual)
- First posted
- 22 Jun 2007 (estimated)
- Results
- Posted 11 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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:
- 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.
- The contact details for reporting of SAEs were clarified.
- Text pertaining to the reporting of spontaneous abortion was removed from the protocol.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Boostrix Group | Experimental | Procedure: Taking of blood samples, Biological: BoostrixSubjects 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). |
| Adacel Group | Active comparator | Procedure: Taking of blood samples, Biological: Boostrix, Biological: AdacelSubjects 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). |
| Control group | Active comparator | Biological: BoostrixSubjects received the first dose of Boostrix vaccine [Tdap](GSK776423) in this study at Year 9. |
Who may qualify
- Ages
- 28 to 73 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
- The following criterion is applicable to subjects willing to consent to vaccination at Year 9 time point in the Boostrix and Adacel groups:
Key exclusion criteria (24 listed)
- 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:
- Administration of Tdap vaccine since the last dose received in the study NCT00346073.
- Administration of Tdap (Boostrix or Adacel) vaccine at any time prior to the administration of Boostrix vaccine in this study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Taking of blood samplesNo 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. | Procedure or surgery | Adacel Group, Boostrix Group |
| BoostrixA single dose of Boostrix was administered in the primary study (NCT00346073). No treatment was given in this study. | Biological | Adacel Group, Boostrix Group, Control group |
| AdacelA single dose of Adacel was administered in the primary study (NCT00346073). No treatment was given in this study. | Biological | Adacel Group |
Primary outcome
Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Greater Than or Equal to (≥) Protocol Specified Cut-off
Time frame: At year 1 after the vaccination in primary study (NCT00346073)
Anti-D cut-off was defined as ≥ 0.1 International Units per milliliter (IU/mL) determined with Enzyme-linked Immunosorbent Assay (ELISA)
Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At year 3 after the vaccination in primary study (NCT00346073)
Anti-D cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA
Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At year 5 after the vaccination in primary study (NCT00346073)
Anti-D cut-off was defined as ≥ 0.1IU/mL as assessed by ELISA.
Number of Subjects With Anti-D Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At Year 9, one month before the booster vaccination.
Anti-D cut-off was defined as ≥ to 0.1IU/mL as assessed by ELISA.
Number of Subjects With Anti-tetanus (Anti-T) Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At year 1 after the vaccination in primary study (NCT00346073)
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At year 3 after the vaccination in primary study (NCT00346073)
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At year 5 after the vaccination in primary study (NCT00346073)
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-T Antibody Concentrations ≥ Protocol Specified Cut-off
Time frame: At Year 9, one month before the booster vaccination.
Anti-T cut-off was defined as ≥ 0.1 IU/mL as assessed by ELISA.
Number of Subjects With Anti-D and Anti-T Concentrations ≥ 0.1 IU/mL and 1 IU/mL
Time frame: At Year 9, one month after the booster vaccination.
Number of subjects with anti-D and anti-T concentrations ≥ 0.1 IU/mL and 1 IU/mL were tabulated
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
Time frame: At Year 9, one month before booster vaccination
Anti-PT, anti-FHA and anti-PRN antibody concentrations were measured by ELISA, tabulated as GMCs and expressed in IU/mL.
Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations
Time frame: At Year 9, one month after the booster vaccination
Anti-PT, anti-FHA and anti-PRN antibody concentrations were measured by ELISA, tabulated as GMCs and expressed in IU/mL.
Booster Response to D and T Antigens
Time frame: At Year 9, one month after the booster vaccination.
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.
Booster Response to PT, FHA and PRN Antigens
Time frame: At Year 9, one month after the booster vaccination.
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
24 secondary outcomes
Number of Subjects With Anti-pertussis Toxoid (PT) Antibody Concentrations Equal to or Above Protocol Specified Cut-off
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Number of Subjects With Anti-PRN Antibody Concentrations Equal to or Above Protocol Specified Cut-off
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-D Antibody Concentration
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-D Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-T Antibody Concentration
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-T Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-PT Antibody Concentration
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-PT Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-FHA Antibody Concentration
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-FHA Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Anti-PRN Antibody Concentration
Time frame: At 1, 3, and 5 years after the vaccination in primary study (NCT00346073)
Anti-PRN Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Alternative Booster Response to Anti-D and Anti-T Antigens
Time frame: At Year 9, one month after booster vaccination
Alternative Booster Responses to Anti-PT, Anti-FHA and Anti-PRN Antigens
Time frame: At Year 9, one month after booster vaccination
Seroprotection Status for Anti-D Antibody Concentration
Time frame: At Year 9, one month before(pre booster) and after the booster vaccination(post booster)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Year 9
Time frame: During the 4-day (Days 0-3) post vaccination period.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms - Year 9
Time frame: During the 4-day (Days 0-3) post vaccination period.
Number of Subjects With Any Large Injection Site Reaction - Year 9
Time frame: During the 4-day (Days 0-3) follow-up period after vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AEs) - Year 9
Time frame: During the 31-day (Days 0-30) post-vaccination period.
Number of Subjects With Serious Adverse Events (SAEs) - Year 9
Time frame: During the 31-day (Days 0-30) post-vaccination period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30197282Brandon 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.
- Derived from this study: PubMed 21945698Weston 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.
- IPD for this study will be made available via the Clinical Study Data Request site.Link provided by the sponsor.
- Redacted with child studies \& includedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD is available via the Clinical Study Data Request site (click on the link provided below)
Related trials for Acellular Pertussis
RecruitingPhase 2
A Phase II Clinical Trial of Absorbed Acellular Pertussis (Two-Component) Diphtheria-Tetanus Combined Vaccine (For Adults and Adolescents)
Pertussis (Whooping Cough), Diphtheria
RecruitingPhase 1/2
A Phase I/II Clinical Trial of the Diphtheria, Tetanus, Acellular Component Pertussis and Sabin Inactivated Poliomyelitis Vaccine Adsorbed
Diphtheria, Pertussis
RecruitingPhase 4
Concurrent Versus Sequential Administration of Tdap and RSV Vaccines in Pregnancy
RSV, Tdap - Tetanus, Diphtheria and Acellular Pertussis Vaccination
Active, not recruitingPhase 3
A Study on the Immune Response and Safety of a Combined Vaccine Against Diphtheria, Tetanus and Acellular Pertussis (dTpa) in Japanese Healthy Pregnant Women
Diphtheria-Tetanus-acellular Pertussis Vaccines
Not yet recruitingObservational study
A Clinical Study on Immunogenicity Persistence of Adsorbed 5-component Acellular Pertussis, Diphtheria and Tetanus Combined Vaccine
Diphtheria, Tetanus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
37 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Taking of blood samples, Boostrix and Adacel in people with Acellular Pertussis and Tetanus, run by GlaxoSmithKline at 37 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Anti-diphtheria (Anti-D) Antibody Concentrations Greater Than or Equal to (≥) Protocol Specified Cut-off (time frame: At year 1 after the vaccination in primary study (NCT00346073)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00489970, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2020.