Tetanus, Acellular Pertussis, Diphtheria, Diphtheria-Tetanus-acellular Pertussis Vaccines
Conditions
Keywords
Boostrix®, adults
Brief summary
This phase IIIb, observer-blind study will evaluate the immunogenicity and safety of GSK Biologicals' Boostrix® vaccine in adults (extending indication) aged 65 years or older.
Interventions
BIOLOGICALBoostrix®
Intramuscular, single dose.
BIOLOGICALDecavac™
Intramuscular, single dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that can and will comply with the requirements of the protocol should be enrolled in the study. * Males or females 65 years of age and older at the time of study entry. * Free of an acute aggravation of the health status as established by medical history and medical history and clinical examination before entering into the study. * Written informed consent from all subjects.
Exclusion criteria
* Administration of a diphtheria-tetanus (Td) booster within the previous 5 years. * Administration of a Tdap vaccine at any time prior to study entry. * History of diphtheria and/or tetanus and/or pertussis disease. * Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding vaccination, or planned use during the entire study period. * Administration of other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study, with the exception of influenza, vaccine, which may be administered at any time up to or during the study period, including the day of study vaccination. * Planned administration of any vaccine not foreseen by the study protocol up to 30 days following vaccination, with the exception of influenza, vaccine, which may be administered at any time up to or during the study period, including the day of study vaccination. Pneumococcal and zoster vaccines can be administered at the discretion of the investigator when the subject comes back at Visit 2. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination or planned administration during the study period. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. * History of serious allergic reaction following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine or any component of the study vaccines. * History of encephalopathy within seven days of administration of a previous booster dose of pertussis vaccine that is not attributable to another identifiable cause. * Progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy: pertussis vaccine should not be administered to individuals with these conditions until a treatment regimen has been established and the condition has stabilized. * Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by clinical evaluation or pre-existing laboratory screening tests. * Acute disease at the time of vaccination. * Administration of immunoglobulins and/or any blood products within the three months preceding vaccination, or planned administration during the study period. * Any medical condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | One month after vaccination. | Antibodies against vaccine antigens assessed were: anti-diphtheria (anti-D) and anti-tetanus (anti-T). Anti-D antibody cut-off value assessed was ≥ 0.1 International Unit per milliliter (IU/mL) Anti-T antibody cut-off values assessed were ≥ 0.1 IU/mL and ≥ 1.0 IU/mL |
| Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Before (PRE) and one month after vaccination (POST) | Concentration for anti-PT, anti-FHA and anti-PRN antibodies given as geometric mean concentration (GMC) in Enzyme-Linked Immuno Sorbent Assay (ELISA) units per millilitre (EL.U/mL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | One month after vaccination | Booster response defined as : For initially seronegative subjects (\< 5 EL.U/mL), antibody concentration ≥ 20 EL.U/mL one month after vaccination. For initially seropositive subjects (≥ 5 EL.U/mL) with pre-vaccination antibody concentration \< 20 EL.U/mL: antibody concentration one month after vaccination ≥ 4 fold the pre-vaccination antibody concentration. For initially seropositive subjects (≥ 5 EL.U/mL) with pre-vaccination antibody concentration ≥ 20 EL.U/mL : antibody concentration one month after vaccination ≥ 2 fold the pre-vaccination antibody concentration. |
| Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | One month after vaccination | Vaccine response using alternative definitions defined as: For initially seronegative subjects (\< 5 EL.U/mL ), antibody concentration ≥ 10 EL.U/mL one month after vaccination. For initially seropositive subjects (≥ 5 EL.U/mL), antibody concentration one month after vaccination ≥ 2 fold the pre-vaccination antibody concentration. |
| Number of Subjects Reporting Solicited Local Symptoms | Within the 4-day (Day 0-3) post-vaccination period | Solicited local symptoms assessed include pain, redness and swelling. |
| Anti-T and Anti-D Antibody Concentrations | Before (PRE) and one month after vaccination (POST) | Concentrations for anti-T and anti-D antibodies given as GMC in IU/mL. |
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | Within the 31-day (Day 0-30) post-vaccination period | An AE is 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. |
| Number of Subjects Reporting Serious Adverse Events (SAE) | From the vaccination up to Day 182 | An SAE is any untoward medical occurrence that: results in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. |
| Number of Subjects Reporting Solicited General Symptoms | Within the 4-day (Day 0-3) post-vaccination period | Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache, and fever |
| Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off | One month after vaccination | Booster response defined as : For initially seronegative subjects (\< 0.1 IU/mL), antibody concentration ≥ 0.4 IU/mL one month after vaccination. For initially seropositive subjects (≥ 0.1 IU/mL): antibody concentration one month after vaccination ≥ 4 fold the pre-vaccination antibody concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Boostrix Group Subjects received a single dose of Boostrix (tetanus toxoids, reduced diphtheria toxoids and acellular pertussis vaccine) | 887 |
| Decavac Group Subjects received a single dose of Decavac (tetanus and diphtheria toxoids vaccine) | 445 |
| Total | 1,332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Boostrix Group | Decavac Group | Total |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 5.35 | 71.9 years STANDARD_DEVIATION 5.62 | 71.7 years STANDARD_DEVIATION 5.44 |
| Sex: Female, Male Female | 478 Participants | 237 Participants | 715 Participants |
| Sex: Female, Male Male | 409 Participants | 208 Participants | 617 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 351 / 887 | 202 / 445 |
| serious Total, serious adverse events | 37 / 887 | 10 / 445 |
Outcome results
Primary
Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration
Concentration for anti-PT, anti-FHA and anti-PRN antibodies given as geometric mean concentration (GMC) in Enzyme-Linked Immuno Sorbent Assay (ELISA) units per millilitre (EL.U/mL)
Time frame: Before (PRE) and one month after vaccination (POST)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PT (PRE) (N=859;433) | 6.6 EL.U/mL |
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PT (POST) (N=852;431) | 49.1 EL.U/mL |
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-FHA (PRE) (N=848;430) | 50.2 EL.U/mL |
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-FHA (POST) (N=835;428) | 689.0 EL.U/mL |
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PRN (PRE) (N=864;439) | 8.1 EL.U/mL |
| Boostrix Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PRN (POST) (N=865;439) | 104.2 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PRN (PRE) (N=864;439) | 7.8 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PT (PRE) (N=859;433) | 6.5 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-FHA (POST) (N=835;428) | 44.4 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PT (POST) (N=852;431) | 6.4 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-PRN (POST) (N=865;439) | 7.7 EL.U/mL |
| Decavac Group | Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration | Anti-FHA (PRE) (N=848;430) | 44.3 EL.U/mL |
Primary
Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value
Antibodies against vaccine antigens assessed were: anti-diphtheria (anti-D) and anti-tetanus (anti-T). Anti-D antibody cut-off value assessed was ≥ 0.1 International Unit per milliliter (IU/mL) Anti-T antibody cut-off values assessed were ≥ 0.1 IU/mL and ≥ 1.0 IU/mL
Time frame: One month after vaccination.
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-D (≥ 0.1 IU/mL) (N= 859;432) | 729 subjects |
| Boostrix Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-T (≥ 0.1 IU/mL) (N= 864;439) | 836 subjects |
| Boostrix Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-T (≥ 1.0 IU/mL) (N= 864;439) | 767 subjects |
| Decavac Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-D (≥ 0.1 IU/mL) (N= 859;432) | 374 subjects |
| Decavac Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-T (≥ 0.1 IU/mL) (N= 864;439) | 428 subjects |
| Decavac Group | Number of Subjects With Antibody Concentration Against Vaccine Antigens, Above a Protocol Defined Cut-off Value | Anti-T (≥ 1.0 IU/mL) (N= 864;439) | 395 subjects |
Secondary
Anti-T and Anti-D Antibody Concentrations
Concentrations for anti-T and anti-D antibodies given as GMC in IU/mL.
Time frame: Before (PRE) and one month after vaccination (POST)
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Boostrix Group | Anti-T and Anti-D Antibody Concentrations | Anti-D (PRE) (N=844;430) | 0.2 IU/mL |
| Boostrix Group | Anti-T and Anti-D Antibody Concentrations | Anti-D (POST) (N=859;432) | 0.9 IU/mL |
| Boostrix Group | Anti-T and Anti-D Antibody Concentrations | Anti-T (PRE) (N=864;439) | 0.6 IU/mL |
| Boostrix Group | Anti-T and Anti-D Antibody Concentrations | Anti-T (POST) (N=864;439) | 4.0 IU/mL |
| Decavac Group | Anti-T and Anti-D Antibody Concentrations | Anti-T (POST) (N=864;439) | 7.1 IU/mL |
| Decavac Group | Anti-T and Anti-D Antibody Concentrations | Anti-D (PRE) (N=844;430) | 0.2 IU/mL |
| Decavac Group | Anti-T and Anti-D Antibody Concentrations | Anti-T (PRE) (N=864;439) | 0.6 IU/mL |
| Decavac Group | Anti-T and Anti-D Antibody Concentrations | Anti-D (POST) (N=859;432) | 0.8 IU/mL |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAE)
An SAE is any untoward medical occurrence that: results in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Time frame: From the vaccination up to Day 182
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boostrix Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 37 subjects |
| Decavac Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 10 subjects |
Secondary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache, and fever
Time frame: Within the 4-day (Day 0-3) post-vaccination period
Population: Analysis was performed on the Total Vaccinated cohort on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 110 subjects |
| Boostrix Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal symptoms | 67 subjects |
| Boostrix Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 101 subjects |
| Boostrix Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 18 subjects |
| Decavac Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 11 subjects |
| Decavac Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 66 subjects |
| Decavac Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 52 subjects |
| Decavac Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal symptoms | 41 subjects |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed include pain, redness and swelling.
Time frame: Within the 4-day (Day 0-3) post-vaccination period
Population: Analysis was performed on the Total Vaccinated cohort on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 190 subjects |
| Boostrix Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 95 subjects |
| Boostrix Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 66 subjects |
| Decavac Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 56 subjects |
| Decavac Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 123 subjects |
| Decavac Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 52 subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An AE is 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.
Time frame: Within the 31-day (Day 0-30) post-vaccination period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boostrix Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 152 subjects |
| Decavac Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 64 subjects |
Secondary
Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off
Booster response defined as : For initially seronegative subjects (\< 5 EL.U/mL), antibody concentration ≥ 20 EL.U/mL one month after vaccination. For initially seropositive subjects (≥ 5 EL.U/mL) with pre-vaccination antibody concentration \< 20 EL.U/mL: antibody concentration one month after vaccination ≥ 4 fold the pre-vaccination antibody concentration. For initially seropositive subjects (≥ 5 EL.U/mL) with pre-vaccination antibody concentration ≥ 20 EL.U/mL : antibody concentration one month after vaccination ≥ 2 fold the pre-vaccination antibody concentration.
Time frame: One month after vaccination
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-PT (N=846;430) | 585 subjects |
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-FHA (N=821;422) | 762 subjects |
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-PRN (N=864;439) | 638 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-PT (N=846;430) | 430 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-FHA (N=821;422) | 7 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off | Anti-PRN (N=864;439) | 9 subjects |
Secondary
Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions.
Vaccine response using alternative definitions defined as: For initially seronegative subjects (\< 5 EL.U/mL ), antibody concentration ≥ 10 EL.U/mL one month after vaccination. For initially seropositive subjects (≥ 5 EL.U/mL), antibody concentration one month after vaccination ≥ 2 fold the pre-vaccination antibody concentration.
Time frame: One month after vaccination
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-PT (N=846;430) | 699 subjects |
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-FHA (N=821;422) | 765 subjects |
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-PRN (N=864;439) | 714 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-PT (N=846;430) | 9 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-FHA (N=821;422) | 8 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentrations Above the Cut-off, Using Alternative Definitions. | Anti-PRN (N=864;439) | 11 subjects |
Secondary
Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off
Booster response defined as : For initially seronegative subjects (\< 0.1 IU/mL), antibody concentration ≥ 0.4 IU/mL one month after vaccination. For initially seropositive subjects (≥ 0.1 IU/mL): antibody concentration one month after vaccination ≥ 4 fold the pre-vaccination antibody concentration.
Time frame: One month after vaccination
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, on subjects with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off | Anti-T (N=863;439) | 438 subjects |
| Boostrix Group | Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off | Anti-D (N=842;428) | 383 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off | Anti-D (N=842;428) | 189 subjects |
| Decavac Group | Number of Subjects With Vaccine Response for Anti-T and Anti-D Antibodies Concentrations Above the Cut-off | Anti-T (N=863;439) | 306 subjects |