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Safety and Immunogenicity in Adults of Revaccination With Adacel® Vaccine 10 Years After a Previous Dose

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ClinicalTrials.gov Identifier: NCT01439165
Recruitment Status : Completed
First Posted : September 23, 2011
Results First Posted : October 9, 2017
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Prevention
Conditions Tetanus
Diphtheria
Pertussis
Whooping Cough
Interventions Biological: Tetanus Toxoid, Diphtheria Toxoid and Pertussis Vaccine
Biological: Tetanus and Diphtheria Toxoids Adsorbed For Adult Use
Enrollment 1330
Recruitment Details Study participants were enrolled from 30 November 2011 to 13 August 2015 at 31 clinic sites in the United States and 2 clinic sites in Canada.
Pre-assignment Details A total of 1330 participants who met all inclusion criteria and no exclusion criteria were randomized; 1327 participants were vaccinated.
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine
Hide Arm/Group Description Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine. Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine).
Period Title: Overall Study
Started 1002 328
Completed 981 326
Not Completed 21 2
Reason Not Completed
Protocol Violation             3             0
Lost to Follow-up             11             1
Withdrawal by Subject             7             1
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine Total
Hide Arm/Group Description Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine. Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine). Total of all reporting groups
Overall Number of Baseline Participants 1002 328 1330
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 328 participants 1330 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1002
 100.0%
328
 100.0%
1330
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age Continuous Number Analyzed 1002 participants 328 participants 1330 participants
28.9  (10.0) 29.2  (10.6) 29  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 328 participants 1330 participants
Female
646
  64.5%
212
  64.6%
858
  64.5%
Male
356
  35.5%
116
  35.4%
472
  35.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1002 participants 328 participants 1330 participants
United States
270
  26.9%
84
  25.6%
354
  26.6%
Canada
732
  73.1%
244
  74.4%
976
  73.4%
1.Primary Outcome
Title Percentage of Participants With Diphtheria and Tetanus Seroprotection
Hide Description Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. Seroprotection was defined as the following: Anti-Diphtheria and Anti-Tetanus ≥ 0.1 IU/mL.
Time Frame 1 month post-booster vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the Per Protocol Analysis Set.
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine
Hide Arm/Group Description:
Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine.
Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine).
Overall Number of Participants Analyzed 948 317
Measure Type: Number
Unit of Measure: Percentage of participants
Tetanus 100.0 100.0
Diphtheria 99.8 99.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine, Td Adsorbed Vaccine
Comments Comparison of anti-tetanus seroprotection rate between the two groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% Confidence Interval (CI) of the difference of seroprotection rates between groups is > -10%
Method of Estimation Estimation Parameter Difference (%) in Adacel-Td Adsorbed
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.4 to 1.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine, Td Adsorbed Vaccine
Comments Comparison of anti-diphtheria seroprotection rates between the two groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of seroprotection rates between groups is > -10%
Method of Estimation Estimation Parameter Difference (%) in Adacel-Td Adsorbed
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
-0.3 to 2.1
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Diphtheria and Tetanus Booster Response
Hide Description Anti-Diphtheria antibodies were assessed by a toxin neutralization test. Anti-Tetanus antibodies were assessed using an enzyme-linked immunosorbent assay. A booster response was defined as a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with pre-vaccination antibody concentrations ≤2.56 IU/mL for diphtheria and ≤ 2.7 IU/mL for tetanus. If the pre vaccination antibody concentrations were > 2.56 IU/mL for diphtheria and > 2.7 IU/mL for tetanus, then a 2-fold increase in response rate was defined as a booster response.
Time Frame 1 month post-booster vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Booster response rates were assessed in the Per Protocol Analysis Set.
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine
Hide Arm/Group Description:
Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine.
Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine).
Overall Number of Participants Analyzed 948 317
Measure Type: Number
Unit of Measure: Percentage of participants
Tetanus Number Analyzed 944 participants 315 participants
74.5 81.6
Diphtheria Number Analyzed 945 participants 315 participants
83.2 84.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine, Td Adsorbed Vaccine
Comments Comparison of the anti-tetanus booster response rates between the two groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10%
Method of Estimation Estimation Parameter Difference (%) in Adacel-Td Adsorbed
Estimated Value -7.12
Confidence Interval (2-Sided) 95%
-12.0 to -1.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine, Td Adsorbed Vaccine
Comments Comparison of the anti-diphteria booster response rates between the two groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10%
Method of Estimation Estimation Parameter Difference (%) in Adacel-Td Adsorbed
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-5.4 to 4.0
Estimation Comments [Not Specified]
3.Primary Outcome
Title Geometric Mean Concentrations (GMC) of Anti Pertussis Antibodies
Hide Description Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin (FHA), Pertactin, Fimbriae types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Anti-pertussis GMCs further to Adacel vaccination was compared to an historical control group with Daptacel (NCT00255047 for pertussis toxoid and PMID 8538705 for FHA, Pertactin and Fimbriae) since Td Adsorbed Vaccine does not contain any pertussis antigens.
Time Frame 1 month post-booster vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean concentrations were assessed in the Per Protocol Analysis Set.
Arm/Group Title Adacel Vaccine
Hide Arm/Group Description:
Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine.
Overall Number of Participants Analyzed 948
Geometric Mean (95% Confidence Interval)
Unit of Measure: Concentrations (1/dil)
Pertussis Toxoid Number Analyzed 935 participants
102
(94.9 to 110)
FHA Number Analyzed 948 participants
209
(200 to 217)
Pertactin Number Analyzed 948 participants
318
(302 to 334)
Fimbriae types 2 and 3 Number Analyzed 948 participants
745
(711 to 781)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of anti-pertussis toxoid GMCs between Adacel and historical control groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the ratio of GMCs between groups is > 0.66
Method of Estimation Estimation Parameter GMC ratio (Adacel/Historical Control)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.92 to 1.18
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the anti-FHA GMCs between Adacel and historical Control groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the ratio of GMCs between groups is > 0.66
Method of Estimation Estimation Parameter GMC Ratio (Adacel/Historical Control)
Estimated Value 5.22
Confidence Interval (2-Sided) 95%
4.51 to 6.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the anti-Pertactin GMCs between Adacel and historical Control groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the ratio of GMCs between groups is > 0.66
Method of Estimation Estimation Parameter GMC Ratio (Adacel/Historical Control)
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
2.46 to 3.51
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the post-vaccination anti-Fimbriae (types 2 and 3) GMCs between Adacel and historical Control groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the ratio of GMCs between groups is > 0.66
Method of Estimation Estimation Parameter GMC Ratio (Adacel/Historical Control)
Estimated Value 2.18
Confidence Interval (2-Sided) 95%
1.84 to 2.60
Estimation Comments [Not Specified]
4.Primary Outcome
Title Percentage of Subjects With Pertussis Antigen Booster Response
Hide Description

Anti-Pertussis antibodies (Pertussis toxoid, Filamentous Hemagglutinin [FHA], Pertactin, Fimbriae (types 2 and 3) were assessed using an enzyme-linked immunosorbent assay. Booster response is defined as a minimum rise in antibody concentration from pre- to post-vaccination. The minimum rise is at least 2 times if the pre-vaccination concentration is above the cutoff value, or at least 4 times if it is at or below the cutoff value.

Anti-pertussis toxoid booster response rates further to Adacel vaccination was compared to an expected booster rates based on study Td506 (PMID 15933223) since Td Adsorbed Vaccine does not contain any pertussis antigens.

Time Frame 1 month post-booster vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Booster response rate was assessed in the Per protocol analysis set
Arm/Group Title Adacel Vaccine
Hide Arm/Group Description:
Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine.
Overall Number of Participants Analyzed 948
Measure Type: Number
Unit of Measure: Percentage of subjects
Pertussis Toxoid Number Analyzed 894 participants
77.5
FHA Number Analyzed 945 participants
68.9
Pertactin Number Analyzed 945 participants
65.3
Fimbriae (types 2 and 3) Number Analyzed 945 participants
56.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments comparison of anti-pertussis toxoid booster response rates was performed between the Adacel and historical groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10% .
Method of Estimation Estimation Parameter Difference (%) Adacel-Expected Booster
Estimated Value 16.12
Confidence Interval (2-Sided) 95%
13.27 to 18.73
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the anti-FHA booster response rates between the Adacel and historical groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10%
Method of Estimation Estimation Parameter Difference (%) Adacel-Expected Booster
Estimated Value -4.21
Confidence Interval (2-Sided) 95%
-7.23 to -1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the anti-Pertactin booster response rates between Adacel and historical groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10% .
Method of Estimation Estimation Parameter Difference (%) Adacel-Expected Booster
Estimated Value -18.61
Confidence Interval (2-Sided) 95%
-21.7 to -15.6
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Adacel Vaccine
Comments Comparison of the anti-Fimbriae (types 2 and 3) booster response rates between Adacel and historical groups
Type of Statistical Test Non-Inferiority
Comments Non-inferiority concluded if the lower limit of the 2-sided 95% CI of the difference of booster response rates between groups is > -10% .
Method of Estimation Estimation Parameter Difference (%) Adacel-Expected Booster
Estimated Value -19.07
Confidence Interval (2-Sided) 95%
-22.3 to -16.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Reporting a Solicited Injection Site or Systemic Reactions
Hide Description Injection site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection site reactions: Pain, Significant, prevents daily activity. Erythema and Swelling, >100 mm. Grade 3 Systemic reactions: Fever, ≥39°C or ≥102.1 F; 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 and systemic reactions were assessed in the Safety Analysis Set.
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine
Hide Arm/Group Description:
Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine.
Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine).
Overall Number of Participants Analyzed 999 328
Measure Type: Number
Unit of Measure: Percentage of participants
Any Injection site Pain Number Analyzed 982 participants 325 participants
87.1 87.4
Grade 3 Injection site Pain Number Analyzed 982 participants 325 participants
3.6 2.8
Any Injection site Erythema Number Analyzed 982 participants 325 participants
6.4 5.5
Grade 3 Injection site Erythema Number Analyzed 982 participants 325 participants
0.2 0
Any Injection site Swelling Number Analyzed 981 participants 325 participants
6.9 8.0
Grade 3 Injection site Swelling Number Analyzed 981 participants 325 participants
0.3 0
Any Fever Number Analyzed 978 participants 325 participants
0.9 1.8
Grade 3 Fever Number Analyzed 978 participants 325 participants
0.2 0.3
Any Headache Number Analyzed 982 participants 325 participants
41.4 39.1
Grade 3 Headache Number Analyzed 982 participants 325 participants
2.6 4.0
Any Malaise Number Analyzed 982 participants 325 participants
33.3 30.8
Grade 3 Malaise Number Analyzed 982 participants 325 participants
3.0 3.7
Any Myalgia Number Analyzed 982 participants 325 participants
58.1 58.2
Grade 3 Myalgia Number Analyzed 982 participants 325 participants
3.0 3.1
Time Frame Adverse event data were collected from Day 0 up to 1 month post-booster vaccination.
Adverse Event Reporting Description Adverse Events were assessed in the Safety Analysis Set
 
Arm/Group Title Adacel Vaccine Td Adsorbed Vaccine
Hide Arm/Group Description Healthy adults <65 years of age who received Adacel 10 years ago received a repeat dose of Adacel vaccine. Healthy adults <65 years of age who received Adacel 10 years ago received TENIVAC® (Td Adsorbed vaccine).
All-Cause Mortality
Adacel Vaccine Td Adsorbed Vaccine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/999 (0.00%)      0/328 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Adacel Vaccine Td Adsorbed Vaccine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/999 (0.80%)      1/328 (0.30%)    
Gastrointestinal disorders     
Abdominal pain * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Crohn's disease * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Intestinal obstruction * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Infections and infestations     
Infectious mononucleosis * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Injury, poisoning and procedural complications     
Upper limb fracture * 1  0/999 (0.00%)  0 1/328 (0.30%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm malignant * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Abortion spontaneous * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pickwickian syndrome * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
Tonsillar haemorrhage * 1  1/999 (0.10%)  1 0/328 (0.00%)  0
1
Term from vocabulary, MedDRA v14
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
Adacel Vaccine Td Adsorbed Vaccine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   855/999 (85.59%)      284/328 (86.59%)    
General disorders     
Injection site Pain  1  855/999 (85.59%)  855 284/328 (86.59%)  284
Injection site Erythema  1  63/999 (6.31%)  63 18/328 (5.49%)  18
Injection site Swelling  1  68/999 (6.81%)  68 26/328 (7.93%)  26
Malaise  1  327/999 (32.73%)  327 100/328 (30.49%)  100
Musculoskeletal and connective tissue disorders     
Myalgia  1  571/999 (57.16%)  571 189/328 (57.62%)  189
Nervous system disorders     
Headache  1  407/999 (40.74%)  407 127/328 (38.72%)  127
1
Term from vocabulary, MedDRA v14
Indicates events were collected by systematic assessment
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
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01439165     History of Changes
Other Study ID Numbers: Td537
U1111-1117-7012 ( Other Identifier: WHO )
First Submitted: September 20, 2011
First Posted: September 23, 2011
Results First Submitted: July 28, 2017
Results First Posted: October 9, 2017
Last Update Posted: July 24, 2018