Diphtheria, Pertussis, Tetanus
Conditions
Keywords
Diphtheria, Tetanus, Pertussis, DTaP vaccine, Adolescents
Brief summary
This study is designed to assess the immunogenicity and safety of DTaP vaccine (BK1301) as a booster dose in adolescents. The purposes of this study are as follows: * To confirm the non-inferiority of BK1301 to Adsorbed Diphtheria-Tetanus Combined Toxoid (DT toxoid) with respect to booster responses for anti-diphtheria toxoid (anti-D) and anti-tetanus toxoid (anti-T) antibodies * To confirm that booster responses for anti-pertussis toxoid (anti-PT) and anti-Filamentous Hemagglutinin (anti-FHA) antibodies are more than 80% of participants received BK1301
Interventions
BIOLOGICALDiphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP vaccine, BK1301)
0.5 mL, subcutaneous injection
BIOLOGICALAdsorbed Diphtheria-Tetanus Combined Toxoid (DT toxoid)
0.1 mL, subcutaneous injection
Sponsors
The Research Foundation for Microbial Diseases of Osaka University
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
11 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 11 or 12 years on the day of injection * Received 3 or 4 doses of DTaP vaccine
Exclusion criteria
* History of pertussis, diphtheria, tetanus * History of anaphylaxis to vaccine components * Serious conditions or diseases of the heart, vein, blood, respiratory, hepar, kidney, digestive system, psychiatric or nervous system * Transfused or received gamma globulin within 3 months, or received high-dose gamma globulin within 6 months before the day of injection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies | pre-vaccination and 28-42 days after vaccination | Booster response was defined as post titer ≥ 0.4 IU/mL and post/pre titer ≥ 4 increase. |
| Percentage of Participants With Booster Responses for Anti-pertussis Toxoid (Anti-PT) and Anti-Filamentous Hemagglutinin (Anti-FHA) Antibodies | pre-vaccination and 28-42 days after vaccination | Booster response was defined as post titer ≥ 20 EU/mL and post/pre titer ≥ 4 increase in a subject with pre titer \< 20 EU/mL, or post/pre titer ≥ 2 increase in a subject with pre titer ≥ 20 EU/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies | 28-42 days after vaccination | — |
| Geometric Mean Titers (GMTs) of Anti-PT and Anti-FHA Antibodies | 28-42 days after vaccination | — |
| Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values | 28-42 days after vaccination | Protocol defined cut-off values were 0.1 IU/mL for anti-D and 0.01 IU/mL for anti-T. |
| Geometric Mean Titer Ratios of Anti-PT and Anti-FHA Antibodies | pre vaccination and 28-42 days after vaccination | Ratios were calculated as 28-42 days after vaccination titers over pre vaccination titers |
| Percentage of Participants With Adverse Events | 28-42 days following vaccination | — |
| Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies | pre vaccination and 28-42 days after vaccination | Ratios were calculated as 28-42 days after vaccination titers over pre vaccination titers |
| Percentage of Participants With Anti-PT and Anti-FHA Antibody Titers Above Protocol Defined Cut-off Values | 28-42 days after vaccination | Protocol defined cut-off values were 10 EU/mL. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BK1301 Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP vaccine, BK1301): 0.5 mL, subcutaneous injection | 224 |
| DT Toxoid Adsorbed Diphtheria-Tetanus Combined Toxoid (DT toxoid): 0.1 mL, subcutaneous injection | 222 |
| Total | 446 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | BK1301 | DT Toxoid | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 224 Participants | 222 Participants | 446 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 113 Participants | 104 Participants | 217 Participants |
| Sex: Female, Male Male | 111 Participants | 118 Participants | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 200 / 223 | 194 / 222 |
| serious Total, serious adverse events | 0 / 223 | 0 / 222 |
Outcome results
Primary
Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies
Booster response was defined as post titer ≥ 0.4 IU/mL and post/pre titer ≥ 4 increase.
Time frame: pre-vaccination and 28-42 days after vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BK1301 | Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies | anti-D | 100.0 percentage of Participants |
| BK1301 | Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies | anti-T | 98.7 percentage of Participants |
| DT Toxoid | Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies | anti-D | 99.5 percentage of Participants |
| DT Toxoid | Percentage of Participants With Booster Responses for Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibodies | anti-T | 97.3 percentage of Participants |
Primary
Percentage of Participants With Booster Responses for Anti-pertussis Toxoid (Anti-PT) and Anti-Filamentous Hemagglutinin (Anti-FHA) Antibodies
Booster response was defined as post titer ≥ 20 EU/mL and post/pre titer ≥ 4 increase in a subject with pre titer \< 20 EU/mL, or post/pre titer ≥ 2 increase in a subject with pre titer ≥ 20 EU/mL.
Time frame: pre-vaccination and 28-42 days after vaccination
Population: The Outcome Measure was only pre-specified for the BK1301 Arm/Group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BK1301 | Percentage of Participants With Booster Responses for Anti-pertussis Toxoid (Anti-PT) and Anti-Filamentous Hemagglutinin (Anti-FHA) Antibodies | anti-PT | 91.0 percentage of Participants |
| BK1301 | Percentage of Participants With Booster Responses for Anti-pertussis Toxoid (Anti-PT) and Anti-Filamentous Hemagglutinin (Anti-FHA) Antibodies | anti-FHA | 91.5 percentage of Participants |
Secondary
Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies
Ratios were calculated as 28-42 days after vaccination titers over pre vaccination titers
Time frame: pre vaccination and 28-42 days after vaccination
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BK1301 | Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies | anti-D | 137.5 titer ratio |
| BK1301 | Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies | anti-T | 47.9 titer ratio |
| DT Toxoid | Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies | anti-D | 106.3 titer ratio |
| DT Toxoid | Geometric Mean Titer Ratios of Anti-D and Anti-T Antibodies | anti-T | 44.3 titer ratio |
Secondary
Geometric Mean Titer Ratios of Anti-PT and Anti-FHA Antibodies
Ratios were calculated as 28-42 days after vaccination titers over pre vaccination titers
Time frame: pre vaccination and 28-42 days after vaccination
Population: The Outcome Measure was only pre-specified for the BK1301 Arm/Group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BK1301 | Geometric Mean Titer Ratios of Anti-PT and Anti-FHA Antibodies | anti-PT | 12.6 titer ratio |
| BK1301 | Geometric Mean Titer Ratios of Anti-PT and Anti-FHA Antibodies | anti-FHA | 8.5 titer ratio |
Secondary
Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies
Time frame: 28-42 days after vaccination
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BK1301 | Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies | anti-D | 20.856 IU/mL |
| BK1301 | Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies | anti-T | 13.378 IU/mL |
| DT Toxoid | Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies | anti-D | 15.581 IU/mL |
| DT Toxoid | Geometric Mean Titers (GMTs) of Anti-D and Anti-T Antibodies | anti-T | 11.638 IU/mL |
Secondary
Geometric Mean Titers (GMTs) of Anti-PT and Anti-FHA Antibodies
Time frame: 28-42 days after vaccination
Population: The Outcome Measure was only pre-specified for the BK1301 Arm/Group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BK1301 | Geometric Mean Titers (GMTs) of Anti-PT and Anti-FHA Antibodies | anti-PT | 241.15 EU/mL |
| BK1301 | Geometric Mean Titers (GMTs) of Anti-PT and Anti-FHA Antibodies | anti-FHA | 344.46 EU/mL |
Secondary
Percentage of Participants With Adverse Events
Time frame: 28-42 days following vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BK1301 | Percentage of Participants With Adverse Events | 90.1 percentage of participants |
| DT Toxoid | Percentage of Participants With Adverse Events | 89.6 percentage of participants |
Secondary
Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values
Protocol defined cut-off values were 0.1 IU/mL for anti-D and 0.01 IU/mL for anti-T.
Time frame: 28-42 days after vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BK1301 | Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values | anti-D | 100.0 percentage of Participants |
| BK1301 | Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values | anti-T | 100.0 percentage of Participants |
| DT Toxoid | Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values | anti-D | 100.0 percentage of Participants |
| DT Toxoid | Percentage of Participants With Anti-D and Anti-T Antibody Titers Above Protocol Defined Cut-off Values | anti-T | 100.0 percentage of Participants |
Secondary
Percentage of Participants With Anti-PT and Anti-FHA Antibody Titers Above Protocol Defined Cut-off Values
Protocol defined cut-off values were 10 EU/mL.
Time frame: 28-42 days after vaccination
Population: The Outcome Measure was only pre-specified for the BK1301 Arm/Group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BK1301 | Percentage of Participants With Anti-PT and Anti-FHA Antibody Titers Above Protocol Defined Cut-off Values | anti-PT | 100.0 percentage of Participants |
| BK1301 | Percentage of Participants With Anti-PT and Anti-FHA Antibody Titers Above Protocol Defined Cut-off Values | anti-FHA | 100.0 percentage of Participants |