Trial Outcomes & Findings for Study of SP306 Given Intramuscularly Compared to DT Given Subcutaneously in Japanese Adolescents 11 - 12 Years Old (NCT NCT02089347)
NCT ID: NCT02089347
Last Updated: 2017-05-30
Results Overview
Diphtheria booster response was defined as a ≥4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.56 IU/mL or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \>2.56 IU/mL. A tetanus booster response is defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.7 IU/mL or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \>2.7 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
COMPLETED
PHASE3
534 participants
Day 28 post-vaccination
2017-05-30
Participant Flow
The study participants were enrolled from 01 March 2014 through 31 May 2014 at 21 clinic centers in Japan.
A total of 533 participants who met all of the inclusion criteria - including having completed childhood vaccination against diphtheria, pertussis and tetanus (i.e., received 4 doses of Japanese-produced DTaP vaccine), and none of the exclusion criteria were randomized and vaccinated in this study.
Participant milestones
| Measure |
SP306 Group
Participants received SP306 vaccine intramuscularly
|
DT Group
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Overall Study
STARTED
|
356
|
178
|
|
Overall Study
COMPLETED
|
355
|
178
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
SP306 Group
Participants received SP306 vaccine intramuscularly
|
DT Group
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Study of SP306 Given Intramuscularly Compared to DT Given Subcutaneously in Japanese Adolescents 11 - 12 Years Old
Baseline characteristics by cohort
| Measure |
SP306 Group
n=356 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=178 Participants
Participants received DT vaccine subcutaneously
|
Total
n=534 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
356 Participants
n=5 Participants
|
178 Participants
n=7 Participants
|
534 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
Age Continuous
|
11.2 Years
STANDARD_DEVIATION 0.4 • n=5 Participants
|
11.2 Years
STANDARD_DEVIATION 0.4 • n=7 Participants
|
11.2 Years
STANDARD_DEVIATION 0.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
183 Participants
n=5 Participants
|
83 Participants
n=7 Participants
|
266 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
173 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
268 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
356 Participants
n=5 Participants
|
178 Participants
n=7 Participants
|
534 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28 post-vaccinationPopulation: Post-vaccination booster response was determined in the per-protocol population
Diphtheria booster response was defined as a ≥4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.56 IU/mL or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \>2.56 IU/mL. A tetanus booster response is defined as a ≥ 4-fold rise in pre- to post-vaccination antitoxin concentration in a subject with a pre-vaccination antitoxin concentration ≤ 2.7 IU/mL or a ≥ 2-fold rise in a subject with a pre-vaccination antitoxin concentration \>2.7 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants With Diphtheria and Tetanus Post-vaccination Booster Response Following Vaccination With Either SP306 or DT
Diphtheria Booster Response
|
99.7 Percentage of Participants
|
98.3 Percentage of Participants
|
|
Percentage of Participants With Diphtheria and Tetanus Post-vaccination Booster Response Following Vaccination With Either SP306 or DT
Tetanus Booster Response
|
100 Percentage of Participants
|
93.8 Percentage of Participants
|
PRIMARY outcome
Timeframe: Day 28 post-vaccinationPopulation: Seroprotection was assessed in the per-protocol population
Seroprotection was defined as the proportion of subjects at 28 days post-vaccination with diphtheria and tetanus antitoxin concentration ≥0.1 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Post-booster Vaccination With Either SP306 or DT Vaccine
Diphtheria
|
100 Percentage of Participants
|
99.4 Percentage of Participants
|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Post-booster Vaccination With Either SP306 or DT Vaccine
Tetanus
|
100 Percentage of Participants
|
100 Percentage of Participants
|
PRIMARY outcome
Timeframe: Day 28 post-vaccinationPopulation: Post-vaccination pertussis booster response was determined in the per-protocol population
Pertussis booster response was defined as a pre-vaccination antibody concentration less than the lower limit of quantitation (LLOQ) and a post vaccination level ≥ 4XLLOQ; or a pre-vaccination antibody concentration ≥ LLOQ but \< 4XLLOQ and a 4-fold rise (i.e. post/pre-vaccination ≥ 4); or a pre-vaccination antibody concentrations ≥ 4XLLOQ and a 2-fold rise (i.e. post/pre-vaccination ≥2). Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method.
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants With Pertussis Booster Response Following Vaccination With Either SP306 or DT Vaccine
Pertussis Toxoid
|
39.1 Percentage of Participants
|
1.1 Percentage of Participants
|
|
Percentage of Participants With Pertussis Booster Response Following Vaccination With Either SP306 or DT Vaccine
Filamentous Hemagglutinin
|
95.1 Percentage of Participants
|
2.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Pre-vaccination (Day 0)Population: Seroprotection was assessed in the per-protocol population
Seroprotection was defined as the proportion of participants with pre-vaccination with diphtheria and tetanus antitoxin concentration ≥ 0.1 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method.
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participation With Seroprotection to Diphtheria and Tetanus Antigens Before Vaccination With Either SP306 or DT Vaccine
Diphtheria
|
46.6 Percentage of Participants
|
46.6 Percentage of Participants
|
|
Percentage of Participation With Seroprotection to Diphtheria and Tetanus Antigens Before Vaccination With Either SP306 or DT Vaccine
Tetanus
|
77.1 Percentage of Participants
|
77.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccinationPopulation: Seroprotection was assessed in the per-protocol population
Seroprotection was defined as the proportion of participants with diphtheria and tetanus antitoxin concentration level ≥ 0.01 IU/mL. Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method.
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine
Diphtheria (Pre-vaccination)
|
97.4 Percentage of Participants
|
97.7 Percentage of Participants
|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine
Diphtheria (Post-vaccination)
|
100 Percentage of Participants
|
99.4 Percentage of Participants
|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine
Tetanus (Pre-vaccination)
|
100 Percentage of Participants
|
99.4 Percentage of Participants
|
|
Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine
Tetanus (Post-vaccination)
|
100 Percentage of Participants
|
100 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccinationPopulation: Geometric Mean Concentration were assessed in the per-protocol population
Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Diphtheria (pre-vaccination)
|
0.10 Titers
Interval 0.09 to 0.12
|
0.10 Titers
Interval 0.08 to 0.12
|
|
Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Diphtheria (post-vaccination)
|
8.64 Titers
Interval 7.78 to 9.59
|
10.08 Titers
Interval 8.29 to 12.26
|
|
Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Tetanus (pre-vaccination)
|
0.25 Titers
Interval 0.22 to 0.27
|
0.24 Titers
Interval 0.2 to 0.28
|
|
Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Tetanus (post-vaccination)
|
26.15 Titers
Interval 24.2 to 28.26
|
7.58 Titers
Interval 6.75 to 8.52
|
SECONDARY outcome
Timeframe: Day 28 post-vaccinationPopulation: Post-vaccination pertussis booster response was determined in the per-protocol population
Pertussis booster response was defined as a pre-vaccination antibody concentration less than the lower limit of quantitation (LLOQ) and a post-vaccination level ≥ 4XLLOQ; or a pre-vaccination antibody concentration ≥ LLOQ but \< 4XLLOQ and a 4-fold rise (i.e. post/pre-vaccination ≥ 4); or a pre-vaccination antibody concentrations ≥ 4XLLOQ and a 2-fold rise (i.e. post/pre-vaccination ≥2). Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method.
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants With Pertussis (Pertactin and Fimbriae Types 2 and 3) Booster Response Following Vaccination With Either SP306 or DT Vaccine
Pertactin
|
90.3 Percentage of Participants
|
0.6 Percentage of Participants
|
|
Percentage of Participants With Pertussis (Pertactin and Fimbriae Types 2 and 3) Booster Response Following Vaccination With Either SP306 or DT Vaccine
Fimbriae Types 2 and 3
|
94.6 Percentage of Participants
|
0.6 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccinationPopulation: Geometric Mean Concentration was assessed in the per-protocol population
Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method
Outcome measures
| Measure |
SP306 Group
n=350 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=176 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Pertussis toxoid (pre-vaccination)
|
6.27 Titers
Interval 5.59 to 7.03
|
6.15 Titers
Interval 5.24 to 7.21
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Pertussis toxoid (post-vaccination)
|
23.83 Titers
Interval 21.59 to 26.3
|
6.07 Titers
Interval 5.16 to 7.13
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Filamentous Hemagglutinin (pre-vaccination)
|
19.14 Titers
Interval 17.01 to 21.55
|
21.55 Titers
Interval 18.41 to 25.22
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Filamentous Hemagglutinin (post-vaccination)
|
160.66 Titers
Interval 149.49 to 172.66
|
21.16 Titers
Interval 18.17 to 24.65
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Pertactin (pre-vaccination)
|
7.02 Titers
Interval 6.15 to 8.01
|
8.20 Titers
Interval 6.74 to 9.98
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Pertactin (post-vaccination)
|
129.59 Titers
Interval 112.15 to 149.73
|
7.94 Titers
Interval 6.52 to 9.67
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Fimbriae (pre-vaccination)
|
3.43 Titers
Interval 3.12 to 3.76
|
3.68 Titers
Interval 3.18 to 4.25
|
|
Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Fimbriae (post-vaccination)
|
233.01 Titers
Interval 198.02 to 274.17
|
3.63 Titers
Interval 3.13 to 4.21
|
SECONDARY outcome
Timeframe: Day 0 up to Day 7 post-vaccinationPopulation: Solicited injection-site reactions and systemic reactions were assessed in the Safety Analysis Set.
Solicited injection-site: Pain, Erythema, Swelling; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 injection-site: Pain Significant, prevents daily activity; Erythema and Swelling \>100 mm. Grade 3 systemic reactions: Fever, \>39˚C; Headache, Malaise, and Myalgia, Significant, prevents daily activity.
Outcome measures
| Measure |
SP306 Group
n=356 Participants
Participants received SP306 vaccine intramuscularly
|
DT Group
n=178 Participants
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Myalgia
|
0.3 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Any Injection-site reaction
|
83.1 Percentage of Participants
|
64.0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Injection-site reaction
|
2.2 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Injection-site Pain
|
80.1 Percentage of Participants
|
48.3 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Injection-site Pain
|
0 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Injection-site Erythema
|
20.2 Percentage of Participants
|
27.5 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Injection-site Erythema
|
1.4 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Injection-site Swelling
|
20.2 Percentage of Participants
|
22.5 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Injection-site Swelling
|
1.4 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Any solicited systemic reaction
|
60.7 Percentage of Participants
|
32.0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Solicited systemic reaction
|
0.8 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Fever
|
9.3 Percentage of Participants
|
2.2 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Fever
|
0.6 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Headache
|
20.5 Percentage of Participants
|
12.4 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Headache
|
0.3 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Malaise
|
23.9 Percentage of Participants
|
13.5 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Grade 3 Malaise
|
0.3 Percentage of Participants
|
0 Percentage of Participants
|
|
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Myalgia
|
44.1 Percentage of Participants
|
20.2 Percentage of Participants
|
Adverse Events
SP306 Group
DT Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SP306 Group
n=356 participants at risk
Participants received SP306 vaccine intramuscularly
|
DT Group
n=178 participants at risk
Participants received DT vaccine subcutaneously
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.1%
18/356 • Number of events 19 • Adverse events data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination.
|
5.6%
10/178 • Number of events 12 • Adverse events data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination.
|
|
General disorders
Injection site Pruritus
|
4.5%
16/356 • Number of events 16 • Adverse events data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination.
|
6.2%
11/178 • Number of events 11 • Adverse events data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications
- Publication restrictions are in place
Restriction type: OTHER