Immunogenicity & Reactogenicity of Boostrix 10 Years After Previous Booster Vaccination in Study NCT01267058

Study Overview
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Brief Summary
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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).

Official Title
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Evaluation of GSK Biologicals' dTpa Booster Vaccine in Adults, Given 10 Years After Previous dTpa Boosting.

Conditions
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Acellular Pertussis, Tetanus, Diphtheria, Diphtheria-Tetanus-acellular Pertussis Vaccines

Intervention / Treatment
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* Biological: Boostrix™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 28 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boostrix I Group<br>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. | Biological: Boostrix™<br>* Intramuscular injection, 1 dose<br>|
| Active Comparator: Boostrix II Group<br>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. | Biological: Boostrix™<br>* Intramuscular injection, 1 dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | One month after the booster vaccination [PI(M1)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | 
| 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). | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | 
| 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. | Prior (PRE) to booster vaccination | 
| Anti-DT and Anti-TT Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). | Prior to the booster vaccination | 
| 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. | Prior the booster vaccination | 
| 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. | Prior the booster vaccination | 
| 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. | Prior the booster vaccination | 
| 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) | Prior the booster vaccination | 
| 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. | Prior to the booster vaccination | 
| 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. | Prior to the booster vaccination | 
| 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. | One month after the booster vaccination | 
| 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. | One month after the booster vaccination | 
| 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. | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | 
| 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). | Prior to (PRE) and one month after [PI(M1)] the booster vaccination | 
| 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). | One month after the booster vaccination | 
| 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. | During the 4-day (Day 0-3) follow-up period after booster vaccination | 
| 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. | During the 4-day (Day 0-3) follow-up period after booster vaccination | 
| 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. | During the 31-day (Day 0-30) follow-up period after booster vaccination | 
| 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. | Following the booster vaccination |