Acellular Pertussis, Diphtheria, Diphtheria-Tetanus-acellular Pertussis Vaccines, Tetanus
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of repeating dTpa booster in adults 10 years after previous booster vaccination with dTpa in a previous clinical study (NCT01267058). Only subjects who received the booster vaccination in a previous clinical study are eligible for participation in this study. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. No new recruitment will be performed in this booster phase (see inclusion criteria).
Interventions
BIOLOGICALBoostrix™
Intramuscular injection, 1 dose
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * Subjects who have received dTpa vaccine or Td and pa vaccines in study 263855/002 . * A male or female subject, recruited 10 years (+/- 9 months) after booster vaccination in study 263855/002. * Healthy subjects as established by medical history and clinical examination before entering into the study. * If the subject is female, she must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of booster vaccination. * Written informed consent obtained from the subject.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the booster dose of study vaccine, or planned use during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose. * Administration of a vaccine not foreseen by the study protocol within 30 days prior to booster vaccination, or planned administration during the active study period * 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 product * Previous booster vaccination against diphtheria, tetanus or pertussis since the last dose received in study 263855/002 * History of diphtheria, tetanus, or pertussis diseases. * Any confirmed or suspected immunosuppressive or immunodeficiency condition, based on medical history and physical examination * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Administration of immunoglobulins and/or any blood products within the three months preceding the booster dose or planned administration during the study period. * Occurrence of transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus. * Occurrence of any of the following adverse event after a previous administration of a DTP vaccine :- hypersensitivity reaction to any component of the vaccine; - encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis-containing vaccine; - fever ≥ 40 °C (axillary temperature) within 48 hours of vaccination not due to another identifiable cause; - collapse or shock-like state within 48 hours of vaccination; - convulsions with or without fever, occurring within 3 days of vaccination. * Acute disease at the time of enrolment. * Pregnant or lactating female. * Female planning to become pregnant or planning to discontinue contraceptive precautions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL) | One month after the booster vaccination [PI(M1)] | Cut-off values defining seroprotected subjects against anti-DT/anti-TT were greater than or equal to (≥) 0.1 IU/mL as assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). The analysis was performed and presents results only for subjects who in the previous study NCT01267058, had received the Boostrix™ vaccine as first booster. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | Concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). |
| Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Prior (PRE) to booster vaccination | Cut-off values, as assessed by ELISA, were greater than or equal to (≥) 0.1 IU/mL and ≥ 1 IU/mL. This endpoint presents results for subjects included in the ATP cohort for antibody persistence. |
| Anti-DT and Anti-TT Antibody Concentrations | Prior to the booster vaccination | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). |
| Number of Seronegative Subjects for Anti-DT Antibodies - ELISA | Prior the booster vaccination | Seronegative subjects were defined as subjects with anti-DT antibody concentrations \< 0.1 IU/mL prior to vaccination, as assessed by ELISA. |
| Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test | Prior the booster vaccination | Sera with ELISA concentrations \<0.1 IU/mL before vaccination were tested for neutralising antibodies using a Vero-cell neutralisation assay. Concentrations ≥0.016 IU/mL by Vero-cell indicated detectable anti-diphteria neutralising antibodies. |
| Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Prior the booster vaccination | Cut-off values, as assessed by ELISA, were greater than or equal to ≥ 5 ELISA Units per millilitre (EL.U/mL) defining seropositive subjects post-vaccination. |
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Prior the booster vaccination | Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL) |
| Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | Cut-off values, as assessed by ELISA, were greater than or equal to (≥) 0.1 IU/mL and (≥) 1 IU/mL. |
| Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test. | Prior to the booster vaccination | Sera with ELISA concentrations \<0.1 IU/mL before vaccination were tested for neutralising antibodies using a Vero-cell neutralisation assay. Concentrations ≥0.016 IU/mL by Vero-cell indicated detectable anti-diphteria neutralising antibodies. |
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | Cut-off values, as assessed by ELISA, were greater than or equal to ≥ 5 ELISA Units per millilitre (EL.U/mL) defining seropositive subjects post-vaccination. |
| Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | One month after the booster vaccination | Booster response was defined as appearance of antibodies in subjects who were seronegative at the pre-vaccination time point (i.e. with concentrations \< 5 El.U/mL) or at least 2-fold increase of pre-vaccination antibody concentrations in subjects who were seropositive at the pre-vaccination time point (i.e. with concentrations ≥5 El.U/mL). |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | During the 4-day (Day 0-3) follow-up period after booster vaccination | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Relationship analysis was not performed. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group. |
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | During the 4-day (Day 0-3) follow-up period after booster vaccination | Assessed solicited general symptoms were fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], headache, gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group. |
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | During the 31-day (Day 0-30) follow-up period after booster vaccination | An unsolicited AE covers any untoward medical occurrence 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group. |
| Number of Subjects With Serious Adverse Events (SAEs) | Following the booster vaccination | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group. |
| Number of Seronegative Subjects for Anti-DT Antibodies - ELISA. | Prior to the booster vaccination | Seronegative subjects were defined as subjects with anti-DT antibody concentrations \< 0.1 IU/mL prior to vaccination, as assessed by ELISA. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Boostrix I Group Subjects who had received the Boostrix™ vaccine in the primary study 263855/002 (NCT01267058), were boosted in the current study with one dose of the same vaccine, intramuscularly in the deltoid region of the non-dominant arm. | 164 |
| Boostrix II Group Subjects who had received the Td vaccines in the primary study 263855/002 (NCT01267058), were boosted in the current study with one dose of the Boostrix™ vaccine intramuscularly in the deltoid region of the non-dominant arm. | 39 |
| Total | 203 |
Baseline characteristics
| Characteristic | Boostrix I Group | Boostrix II Group | Total |
|---|---|---|---|
| Age, Continuous | 50.1 Years STANDARD_DEVIATION 9.98 | 51.0 Years STANDARD_DEVIATION 8.7 | 50.27 Years STANDARD_DEVIATION 9.73 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 107 Participants | 33 Participants | 140 Participants |
| Sex: Female, Male Male | 57 Participants | 6 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 203 |
| other Total, other adverse events | 163 / 203 |
| serious Total, serious adverse events | 0 / 203 |
Outcome results
Primary
Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL)
Cut-off values defining seroprotected subjects against anti-DT/anti-TT were greater than or equal to (≥) 0.1 IU/mL as assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). The analysis was performed and presents results only for subjects who in the previous study NCT01267058, had received the Boostrix™ vaccine as first booster.
Time frame: One month after the booster vaccination [PI(M1)]
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL) | Anti-DT ≥ 0.1 PI(M1) | 151 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL) | Anti-TT ≥ 0.1 PI(M1) | 153 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL) | Anti-DT ≥ 0.1 PI(M1) | 35 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations Equal to or Above (≥) 0.1 International Units Per Milliliter (IU/mL) | Anti-TT ≥ 0.1 PI(M1) | 35 Participants |
Secondary
Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
Time frame: Prior to (PRE) and one month after [PI(M1)] the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix I Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-DT, PRE | 0.200 IU/mL |
| Boostrix I Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-DT, PI(M1) | 1.889 IU/mL |
| Boostrix I Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-TT, PRE | 1.026 IU/mL |
| Boostrix I Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-TT, PI(M1) | 6.927 IU/mL |
| Boostrix II Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-TT, PI(M1) | 5.933 IU/mL |
| Boostrix II Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-DT, PRE | 0.233 IU/mL |
| Boostrix II Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-TT, PRE | 0.845 IU/mL |
| Boostrix II Group | Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Anti-DT, PI(M1) | 1.605 IU/mL |
Secondary
Anti-DT and Anti-TT Antibody Concentrations
Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
Time frame: Prior to the booster vaccination
Population: The ATP cohort for antibody persistence included all subjects who had not received any additional dose of DTP vaccine after the booster dose received in study 263855/002 (dTpa-002), with no evidence of diphtheria, tetanus, or pertussis infection or disease, and for whom serological results were available at the pre-booster blood sampling time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix I Group | Anti-DT and Anti-TT Antibody Concentrations | Anti-DT, PRE | 0.208 IU/mL |
| Boostrix I Group | Anti-DT and Anti-TT Antibody Concentrations | Anti-TT, PRE | 1.031 IU/mL |
| Boostrix II Group | Anti-DT and Anti-TT Antibody Concentrations | Anti-DT, PRE | 0.235 IU/mL |
| Boostrix II Group | Anti-DT and Anti-TT Antibody Concentrations | Anti-TT, PRE | 0.898 IU/mL |
Secondary
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL).
Time frame: Prior to (PRE) and one month after [PI(M1)] the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA, PRE | 140.2 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN, PRE | 56.2 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT, PI(M1) | 126.5 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN, PI(M1) | 303.6 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT, PRE | 13.9 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA, PI(M1) | 615.3 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN, PI(M1) | 370.7 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT, PI(M1) | 120.8 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA, PRE | 119.3 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA, PI(M1) | 677.4 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN, PRE | 45.7 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT, PRE | 8.4 EL.U/mL |
Secondary
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EL.U/mL)
Time frame: Prior the booster vaccination
Population: The ATP cohort for antibody persistence included all subjects who had not received any additional dose of DTP vaccine after the booster dose received in study 263855/002 (dTpa-002), with no evidence of diphtheria, tetanus, or pertussis infection or disease, and for whom serological results were available at the pre-booster blood sampling time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT | 13.9 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA | 137.2 EL.U/mL |
| Boostrix I Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN | 56.6 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PT | 8.3 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-FHA | 115.6 EL.U/mL |
| Boostrix II Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Anti-PRN | 50.2 EL.U/mL |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - ELISA
Seronegative subjects were defined as subjects with anti-DT antibody concentrations \< 0.1 IU/mL prior to vaccination, as assessed by ELISA.
Time frame: Prior the booster vaccination
Population: The ATP cohort for antibody persistence included all subjects who had not received any additional dose of DTP vaccine after the booster dose received in study 263855/002 (dTpa-002), with no evidence of diphtheria, tetanus, or pertussis infection or disease, and for whom serological results were available at the pre-booster blood sampling time point
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA | 56 Participants |
| Boostrix II Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA | 14 Participants |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - ELISA
Seronegative subjects were defined as subjects with anti-DT antibody concentrations \< 0.1 IU/mL prior to vaccination, as assessed by ELISA.
Time frame: One month after the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA | 1 Participants |
| Boostrix II Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA | 0 Participants |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - ELISA.
Seronegative subjects were defined as subjects with anti-DT antibody concentrations \< 0.1 IU/mL prior to vaccination, as assessed by ELISA.
Time frame: Prior to the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA. | 56 Participants |
| Boostrix II Group | Number of Seronegative Subjects for Anti-DT Antibodies - ELISA. | 14 Participants |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test
Sera with ELISA concentrations \<0.1 IU/mL before vaccination were tested for neutralising antibodies using a Vero-cell neutralisation assay. Concentrations ≥ 0.016 IU/mL by Vero-cell indicated detectable anti-diphteria neutralising antibodies.
Time frame: One month after the booster vaccination
Population: This analysis was performed on those participants from the According to Protocol (ATP) cohort for immunogenicity who were found to be seronegative for anti-diphtheria antibodies as assessed by ELISA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test | 0 Participants |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test
Sera with ELISA concentrations \<0.1 IU/mL before vaccination were tested for neutralising antibodies using a Vero-cell neutralisation assay. Concentrations ≥0.016 IU/mL by Vero-cell indicated detectable anti-diphteria neutralising antibodies.
Time frame: Prior the booster vaccination
Population: This analysis was performed on those participants from the According to Protocol (ATP) cohort for antibody persistence who were found to be seronegative for anti-diphtheria antibodies as tested by ELISA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test | 16 Participants |
| Boostrix II Group | Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test | 4 Participants |
Secondary
Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test.
Sera with ELISA concentrations \<0.1 IU/mL before vaccination were tested for neutralising antibodies using a Vero-cell neutralisation assay. Concentrations ≥0.016 IU/mL by Vero-cell indicated detectable anti-diphteria neutralising antibodies.
Time frame: Prior to the booster vaccination
Population: This analysis was performed on those participants from the According to Protocol (ATP) cohort for immunogenicity who were found to be seronegative for anti-diphtheria antibodies as assessed by ELISA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test. | 16 Participants |
| Boostrix II Group | Number of Seronegative Subjects for Anti-DT Antibodies - Neutralisation Test. | 4 Participants |
Secondary
Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies
Cut-off values, as assessed by ELISA, were greater than or equal to ≥ 5 ELISA Units per millilitre (EL.U/mL) defining seropositive subjects post-vaccination.
Time frame: Prior the booster vaccination
Population: The ATP cohort for antibody persistence included all subjects who had not received any additional dose of DTP vaccine after the booster dose received in study 263855/002 (dTpa-002), with no evidence of diphtheria, tetanus, or pertussis infection or disease, and for whom serological results were available at the pre-booster blood sampling time point
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-PT | 137 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-FHA | 159 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-PRN | 151 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-PT | 23 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-FHA | 37 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies | Anti-PRN | 33 Participants |
Secondary
Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies
Cut-off values, as assessed by ELISA, were greater than or equal to ≥ 5 ELISA Units per millilitre (EL.U/mL) defining seropositive subjects post-vaccination.
Time frame: Prior to (PRE) and one month after [PI(M1)] the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PT, PRE | 131 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PT, PI(M1) | 152 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-FHA, PRE | 152 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-FHA, PI(M1) | 152 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PRN, PRE | 144 Participants |
| Boostrix I Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PRN, PI(M1) | 153 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PRN, PRE | 31 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PT, PRE | 22 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-FHA, PI(M1) | 35 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PT, PI(M1) | 35 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-PRN, PI(M1) | 34 Participants |
| Boostrix II Group | Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Anti-FHA, PRE | 35 Participants |
Secondary
Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values
Cut-off values, as assessed by ELISA, were greater than or equal to (≥) 0.1 IU/mL and (≥) 1 IU/mL.
Time frame: Prior to (PRE) and one month after [PI(M1)] the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PRE | 95 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PI(M1) | 151 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PRE | 24 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PI(M1) | 106 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PRE | 145 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PI(M1) | 153 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PRE | 90 Participants |
| Boostrix I Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PI(M1) | 153 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PI(M1) | 35 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PRE | 20 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PRE | 30 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PI(M1) | 35 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PRE | 23 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PRE | 7 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PI(M1) | 35 Participants |
| Boostrix II Group | Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PI(M1) | 23 Participants |
Secondary
Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values
Cut-off values, as assessed by ELISA, were greater than or equal to (≥) 0.1 IU/mL and ≥ 1 IU/mL. This endpoint presents results for subjects included in the ATP cohort for antibody persistence.
Time frame: Prior (PRE) to booster vaccination
Population: The ATP cohort for antibody persistence included all subjects who had not received any additional dose of DTP vaccine after the booster dose received in study 263855/002 (dTpa-002), with no evidence of diphtheria, tetanus, or pertussis infection or disease, and for whom serological results were available at the pre-booster blood sampling time point
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PRE | 102 Participants |
| Boostrix I Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PRE | 25 Participants |
| Boostrix I Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PRE | 152 Participants |
| Boostrix I Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PRE | 95 Participants |
| Boostrix II Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 1 IU/mL, PRE | 25 Participants |
| Boostrix II Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 0.1 IU/mL, PRE | 22 Participants |
| Boostrix II Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-TT ≥ 0.1 IU/mL, PRE | 32 Participants |
| Boostrix II Group | Number of Subjects With Anti-DT and Anti-TT Antibody Concentrations Equal to or Above Cut-off Values | Anti-DT ≥ 1 IU/mL, PRE | 7 Participants |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Relationship analysis was not performed. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group.
Time frame: During the 4-day (Day 0-3) follow-up period after booster vaccination
Population: The Total Vaccinated Cohort (TVC) included all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 72 Participants |
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 14 Participants |
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 66 Participants |
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 20 Participants |
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 142 Participants |
| Boostrix I Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 2 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were fatigue, fever \[defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)\], headache, gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group.
Time frame: During the 4-day (Day 0-3) follow-up period after booster vaccination
Population: The Total Vaccinated Cohort (TVC) included all vaccinated subjects for whom data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue | 47 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue | 0 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue | 25 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fever | 6 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fever | 0 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fever | 5 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptom | 15 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptom | 1 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptom | 7 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache | 39 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache | 2 Participants |
| Boostrix I Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache | 18 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group.
Time frame: During the 31-day (Day 0-30) follow-up period after booster vaccination
Population: The Total Vaccinated Cohort (TVC) included all vaccinated subjects for whom data were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 35 Participants |
Secondary
Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN
Booster response was defined as appearance of antibodies in subjects who were seronegative at the pre-vaccination time point (i.e. with concentrations \< 5 El.U/mL) or at least 2-fold increase of pre-vaccination antibody concentrations in subjects who were seropositive at the pre-vaccination time point (i.e. with concentrations ≥5 El.U/mL).
Time frame: One month after the booster vaccination
Population: The ATP cohort for immunogenicity included all evaluable subjects who had received the booster dose of Boostrix™ vaccine and for whom immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-vaccination blood-sampling time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boostrix I Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-PT | 148 Participants |
| Boostrix I Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-FHA | 119 Participants |
| Boostrix I Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-PRN | 106 Participants |
| Boostrix II Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-PT | 33 Participants |
| Boostrix II Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-FHA | 31 Participants |
| Boostrix II Group | Number of Subjects With Booster Response to Anti-PT, Anti-FHA and Anti-PRN | Anti-PRN | 26 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. For safety assessment Boostrix I Group and Boostrix II Group were pooled into Booster Pooled Group.
Time frame: Following the booster vaccination
Population: The Total Vaccinated Cohort (TVC) included all vaccinated subjects for whom data were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Boostrix I Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |