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Study of SP306 Given Intramuscularly Compared to DT Given Subcutaneously in Japanese Adolescents 11 - 12 Years Old

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ClinicalTrials.gov Identifier: NCT02089347
Recruitment Status : Completed
First Posted : March 17, 2014
Results First Posted : October 8, 2015
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Tetanus
Diphtheria
Pertussis
Interventions Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed
Biological: Diphtheria and Tetanus toxoids adsorbed
Enrollment 534
Recruitment Details The study participants were enrolled from 01 March 2014 through 31 May 2014 at 21 clinic centers in Japan.
Pre-assignment Details 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.
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description Participants received SP306 vaccine intramuscularly Participants received DT vaccine subcutaneously
Period Title: Overall Study
Started 356 178
Completed 355 178
Not Completed 1 0
Reason Not Completed
Protocol Violation             1             0
Arm/Group Title SP306 Group DT Group Total
Hide Arm/Group Description Participants received SP306 vaccine intramuscularly Participants received DT vaccine subcutaneously Total of all reporting groups
Overall Number of Baseline Participants 356 178 534
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 178 participants 534 participants
<=18 years
356
 100.0%
178
 100.0%
534
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age Continuous Number Analyzed 356 participants 178 participants 534 participants
11.2  (0.4) 11.2  (0.4) 11.2  (0.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 356 participants 178 participants 534 participants
Female
183
  51.4%
83
  46.6%
266
  49.8%
Male
173
  48.6%
95
  53.4%
268
  50.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 356 participants 178 participants 534 participants
356 178 534
1.Primary Outcome
Title Percentage of Participants With Diphtheria and Tetanus Post-vaccination Booster Response Following Vaccination With Either SP306 or DT
Hide Description

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

Time Frame Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Post-vaccination booster response was determined in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Diphtheria Booster Response 99.7 98.3
Tetanus Booster Response 100 93.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SP306 Group, DT Group
Comments Non-inferiority comparison of post-booster response for Diphtheria.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority is supported by a data if the lower bound of the two-sided 95% confidence interval (CI) is greater than -10%
Method of Estimation Estimation Parameter Wilson score method
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
-0.31 to 4.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SP306 Group, DT Group
Comments Non-inferiority comparison of post-vaccination booster response for tetanus
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority is supported by the data if lower bound ot the two-sided 95% is greater than -10%
Method of Estimation Estimation Parameter Wilson score method
Estimated Value 6.25
Confidence Interval (2-Sided) 95%
3.32 to 10.84
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Post-booster Vaccination With Either SP306 or DT Vaccine
Hide Description

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

Time Frame Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Diphtheria 100 99.4
Tetanus 100 100
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SP306 Group, DT Group
Comments Non-inferiority comparison of Diphtheria post-vaccination seroprotection rates at ≥ 0.1 IU/mL
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority is supported by a data if the lower bound of the two-sided 95% confidence interval (CI) is greater than -10%
Method of Estimation Estimation Parameter Wilson score method
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
-0.61 to 3.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SP306 Group, DT Group
Comments Non-inferiority comparison of Tetanus post-vaccination seroprotection rates at ≥ 0.1 IU/mL
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority is supported by a data if the lower bound of the two-sided 95% confidence interval (CI) is greater than -10%.
Method of Estimation Estimation Parameter Wilson score method
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-1.09 to 2.14
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants With Pertussis Booster Response Following Vaccination With Either SP306 or DT Vaccine
Hide Description

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.

Time Frame Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Post-vaccination pertussis booster response was determined in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Pertussis Toxoid 39.1 1.1
Filamentous Hemagglutinin 95.1 2.3
4.Secondary Outcome
Title Percentage of Participation With Seroprotection to Diphtheria and Tetanus Antigens Before Vaccination With Either SP306 or DT Vaccine
Hide Description

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.

Time Frame Pre-vaccination (Day 0)
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Diphtheria 46.6 46.6
Tetanus 77.1 77.8
5.Secondary Outcome
Title Percentage of Participants With Seroprotection to Diphtheria and Tetanus Antigens Before and Following Vaccination With Either SP306 or DT Vaccine
Hide Description

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.

Time Frame Day 0 (pre-vaccination) and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Diphtheria (Pre-vaccination) 97.4 97.7
Diphtheria (Post-vaccination) 100 99.4
Tetanus (Pre-vaccination) 100 99.4
Tetanus (Post-vaccination) 100 100
6.Secondary Outcome
Title Geometric Mean Concentration of Diphtheria and Tetanus Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Hide Description Diphtheria antitoxin concentration was assayed by the toxin neutralization test; Tetanus antitoxin concentration was assayed by the enzyme-linked immunosorbent assay (ELISA) method
Time Frame Day 0 (pre-vaccination) and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric Mean Concentration were assessed in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Diphtheria (pre-vaccination)
0.10
(0.09 to 0.12)
0.10
(0.08 to 0.12)
Diphtheria (post-vaccination)
8.64
(7.78 to 9.59)
10.08
(8.29 to 12.26)
Tetanus (pre-vaccination)
0.25
(0.22 to 0.27)
0.24
(0.20 to 0.28)
Tetanus (post-vaccination)
26.15
(24.20 to 28.26)
7.58
(6.75 to 8.52)
7.Secondary Outcome
Title Percentage of Participants With Pertussis (Pertactin and Fimbriae Types 2 and 3) Booster Response Following Vaccination With Either SP306 or DT Vaccine
Hide Description

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.

Time Frame Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Post-vaccination pertussis booster response was determined in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Measure Type: Number
Unit of Measure: Percentage of Participants
Pertactin 90.3 0.6
Fimbriae Types 2 and 3 94.6 0.6
8.Secondary Outcome
Title Geometric Mean Concentration of Pertussis Antibodies Before and Following Vaccination With Either SP306 or DT Vaccine
Hide Description Pertussis antitoxin concentration were assayed by the enzyme-linked immunosorbent assay (ELISA) method
Time Frame Day 0 (pre-vaccination) and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric Mean Concentration was assessed in the per-protocol population
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 350 176
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Pertussis toxoid (pre-vaccination)
6.27
(5.59 to 7.03)
6.15
(5.24 to 7.21)
Pertussis toxoid (post-vaccination)
23.83
(21.59 to 26.30)
6.07
(5.16 to 7.13)
Filamentous Hemagglutinin (pre-vaccination)
19.14
(17.01 to 21.55)
21.55
(18.41 to 25.22)
Filamentous Hemagglutinin (post-vaccination)
160.66
(149.49 to 172.66)
21.16
(18.17 to 24.65)
Pertactin (pre-vaccination)
7.02
(6.15 to 8.01)
8.20
(6.74 to 9.98)
Pertactin (post-vaccination)
129.59
(112.15 to 149.73)
7.94
(6.52 to 9.67)
Fimbriae (pre-vaccination)
3.43
(3.12 to 3.76)
3.68
(3.18 to 4.25)
Fimbriae (post-vaccination)
233.01
(198.02 to 274.17)
3.63
(3.13 to 4.21)
9.Secondary Outcome
Title Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following a Single Booster Dose of SP306 or DT Vaccine
Hide Description 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.
Time Frame Day 0 up to Day 7 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited injection-site reactions and systemic reactions were assessed in the Safety Analysis Set.
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description:
Participants received SP306 vaccine intramuscularly
Participants received DT vaccine subcutaneously
Overall Number of Participants Analyzed 356 178
Measure Type: Number
Unit of Measure: Percentage of Participants
Any Injection-site reaction 83.1 64.0
Grade 3 Injection-site reaction 2.2 0
Injection-site Pain 80.1 48.3
Grade 3 Injection-site Pain 0 0
Injection-site Erythema 20.2 27.5
Grade 3 Injection-site Erythema 1.4 0
Injection-site Swelling 20.2 22.5
Grade 3 Injection-site Swelling 1.4 0
Any solicited systemic reaction 60.7 32.0
Grade 3 Solicited systemic reaction 0.8 0
Fever 9.3 2.2
Grade 3 Fever 0.6 0
Headache 20.5 12.4
Grade 3 Headache 0.3 0
Malaise 23.9 13.5
Grade 3 Malaise 0.3 0
Myalgia 44.1 20.2
Grade 3 Myalgia 0.3 0
Time Frame Adverse events data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SP306 Group DT Group
Hide Arm/Group Description Participants received SP306 vaccine intramuscularly Participants received DT vaccine subcutaneously
All-Cause Mortality
SP306 Group DT Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
SP306 Group DT Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/356 (0.00%)      0/178 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
SP306 Group DT Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/356 (5.34%)      12/178 (6.74%)    
General disorders     
Injection site Pruritus * 1  16/356 (4.49%)  16 11/178 (6.18%)  11
Infections and infestations     
Nasopharyngitis * 1  18/356 (5.06%)  19 10/178 (5.62%)  12
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
EMail: RegistryContactUs@sanofipasteur.com
Layout table for additonal information
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT02089347    
Other Study ID Numbers: Td536 (EFC12579)
U1111-1124-7550 ( Other Identifier: WHO )
First Submitted: March 13, 2014
First Posted: March 17, 2014
Results First Submitted: September 9, 2015
Results First Posted: October 8, 2015
Last Update Posted: May 30, 2017