Clinical Trial Results:
Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially with Adacel® in Healthy Subjects Aged 9 to 60 Years in the Philippines
Summary
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EudraCT number |
2019-003136-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
10 Dec 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Jun 2020
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First version publication date |
21 Jun 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CYD66
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02992418 | ||
WHO universal trial number (UTN) |
U1111-1161-3294 | ||
Sponsors
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Sponsor organisation name |
Sanofi Pasteur
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Sponsor organisation address |
14, Espace Henry Vallée, Lyon, France, 69007
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Public contact |
Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Apr 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Dec 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
- To demonstrate the non-inferiority of the humoral immune response to the Tetanus Toxoid (T), Reduced Diphtheria Toxoid (D) and Acellular Pertussis Vaccine Adsorbed (ap) (Tdap) booster dose concomitantly administered with the first dose of CYD dengue vaccine as compared to sequential administration, measured 28 days after Tdap booster dose.
- To demonstrate the non-inferiority of the humoral immune response to the first dose of CYD dengue vaccine concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the first dose of CYD dengue vaccine.
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Protection of trial subjects |
Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Dec 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Philippines: 688
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Worldwide total number of subjects |
688
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
172
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Adolescents (12-17 years) |
172
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Adults (18-64 years) |
344
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study subjects were enrolled from 19 December 2016 to 17 April 2017 at 4 centres in the Philippines. A total of 688 subjects were enrolled and randomised in this study. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Safety signal was identified in seronegative subjects, which led to IDMC recommendation to not vaccinate them anymore. As no Health Authority feedback was received on amendment 1, study was stopped prematurely before 3rd (last) injection of CYD dengue vaccine and no subjects received 3rd CYD dengue dose. All subjects were followed for safety. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) | ||||||||||||||||||||||||
Arm description |
Subjects received 1 booster dose of Tdap vaccine 0.5 millilitre (mL) intramuscular (IM) injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL subcutaneous (SC) injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap)
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Investigational medicinal product code |
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Other name |
Adacel®
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5 mL, IM injection at Month 1.
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Investigational medicinal product name |
CYD Dengue Vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, SC injection at Month 1 and Month 7, respectively.
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Arm title
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CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration) | ||||||||||||||||||||||||
Arm description |
Subjects received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap)
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Investigational medicinal product code |
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Other name |
Adacel®
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5 mL, IM injection at Month 1.
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Investigational medicinal product name |
CYD Dengue Vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, SC injection at Month 1 and Month 7, respectively.
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Baseline characteristics reporting groups
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Reporting group title |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)
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Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 millilitre (mL) intramuscular (IM) injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL subcutaneous (SC) injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)
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Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 millilitre (mL) intramuscular (IM) injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL subcutaneous (SC) injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7. | ||
Reporting group title |
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7. |
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End point title |
Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Subjects | ||||||||||||||||||||||||
End point description |
GMCs against each pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM2+3]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/millilitre (EU/mL). Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Analysis was performed on per protocol analysis set of Tdap (PPT) population which included subjects who received at least one dose of Tdap and had no relevant protocol deviations. Here, 'n' = subjects with available data for each specified category.
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End point type |
Primary
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End point timeframe |
28 days after Tdap vaccination
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Statistical analysis title |
Anti-PT | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||
Point estimate |
0.848
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.721 | ||||||||||||||||||||||||
upper limit |
0.997 | ||||||||||||||||||||||||
Notes [1] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval (CI) of the ratio of GMCs between groups (Group 1/ Group 2) was greater than (>) 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority. |
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Statistical analysis title |
Anti-FHA | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||
Point estimate |
1.02
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.892 | ||||||||||||||||||||||||
upper limit |
1.18 | ||||||||||||||||||||||||
Notes [2] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority. |
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Statistical analysis title |
Anti-PRN | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||
Point estimate |
1.11
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.836 | ||||||||||||||||||||||||
upper limit |
1.46 | ||||||||||||||||||||||||
Notes [3] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority. |
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Statistical analysis title |
Anti-FIM2+3 | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||
Point estimate |
1.05
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.827 | ||||||||||||||||||||||||
upper limit |
1.33 | ||||||||||||||||||||||||
Notes [4] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority. |
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End point title |
Percentage of Subjects With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Subjects | ||||||||||||||||||
End point description |
Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration superior to 0.1 international units (IU)/mL. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Analysis was performed on PPT population. Here, ‘n’=subjects with available data for each specified category.
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End point type |
Primary
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End point timeframe |
28 days after Tdap vaccination
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Statistical analysis title |
Anti-D | ||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | ||||||||||||||||||
Method |
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Parameter type |
Percentage difference | ||||||||||||||||||
Point estimate |
0.26
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-4.53 | ||||||||||||||||||
upper limit |
5.04 | ||||||||||||||||||
Notes [5] - The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference was > -10% for all antigens. |
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Statistical analysis title |
Anti-T | ||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration) v CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)
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Number of subjects included in analysis |
626
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [6] | ||||||||||||||||||
Method |
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Parameter type |
Percentage difference | ||||||||||||||||||
Point estimate |
-0.66
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.87 | ||||||||||||||||||
upper limit |
1.37 | ||||||||||||||||||
Notes [6] - The non-inferiority was demonstrated if the lower limit of all the 95% CI of the difference was > -10% for all antigens. |
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End point title |
Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||
End point description |
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution. Analysis was performed on per-protocol analysis set for CYD dengue vaccine (PPC) population which included subjects who received the first dose of CYD dengue vaccine and had no relevant protocol deviations.
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End point type |
Primary
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End point timeframe |
28 days after first CYD dengue vaccination
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Statistical analysis title |
Serotype 1 | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
620
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [7] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMT ratio | ||||||||||||||||||||||||
Point estimate |
1.11
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.862 | ||||||||||||||||||||||||
upper limit |
1.44 | ||||||||||||||||||||||||
Notes [7] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority. |
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Statistical analysis title |
Serotype 2 | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
620
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [8] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMT ratio | ||||||||||||||||||||||||
Point estimate |
1.19
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.97 | ||||||||||||||||||||||||
upper limit |
1.47 | ||||||||||||||||||||||||
Notes [8] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority. |
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Statistical analysis title |
Serotype 3 | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
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Number of subjects included in analysis |
620
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [9] | ||||||||||||||||||||||||
Method |
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Parameter type |
GMT ratio | ||||||||||||||||||||||||
Point estimate |
0.925
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.739 | ||||||||||||||||||||||||
upper limit |
1.16 | ||||||||||||||||||||||||
Notes [9] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority. |
|||||||||||||||||||||||||
Statistical analysis title |
Serotype 4 | ||||||||||||||||||||||||
Comparison groups |
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) v CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
620
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
non-inferiority [10] | ||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||
Parameter type |
GMT ratio | ||||||||||||||||||||||||
Point estimate |
0.802
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.644 | ||||||||||||||||||||||||
upper limit |
0.999 | ||||||||||||||||||||||||
Notes [10] - The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority. |
|
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End point title |
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||||||||||||||
End point description |
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution. Analysis was performed on the subset of FAS population who received at least one dose of the study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'number of subjects analysed'=subjects evaluable for this end-point and ‘n’=subjects with available data for each specified category.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Pre-vaccination 1) and 28 days after the first CYD dengue vaccination
|
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|
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No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After first Dose of CYD Dengue Vaccination in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||||||||||||||
End point description |
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Analysis was performed on the subset of FAS population who were immune to dengue at baseline. Here, 'number of subjects analysed'=subjects evaluable for this end-point and ‘n’=subjects with available data for each specified category.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Pre-vaccination 1) and 28 days after the first CYD dengue vaccination
|
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|
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No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Neutralizing Antibody Titers Above Pre-defined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) were measured by PRNT50. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Percentage of subjects with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dilution]) against at least 1, 2, 3, or 4 serotypes of CYD were reported. Analysis was performed on the subset of FAS population who were immune to dengue at baseline. Here, 'number of subjects analysed'=subjects evaluable for this end-point and ‘n’=subjects with available data for each specified categories. Here, 'dil'=dilution and "vac"=vaccination in the specified categories.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Pre-vaccination 1) and 28 days after the first CYD dengue vaccination
|
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|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the dose of Tdap Vaccine in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||||||||||||||
End point description |
GMCs against each pertussis antigens (PT, FHA, PRN, FIM2+3) were assessed using ELISA assay method and were measured in EU/mL. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Analysis was performed on the subset of FAS population who were immune to dengue at baseline. Here, 'number of subjects analysed'=subjects evaluable for this end-point and 'n' = subjects with available data for each specified category.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Pre-vaccination) and 28 days after the Tdap vaccination
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects Achieving Serum Antibody Concentration (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Subjects | ||||||||||||||||||||||||
End point description |
The GMC against diphtheria and tetanus antigens was performed by MIT-TNA and ELISA, respectively. Dengue immune subjects at Baseline were defined as subjects with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Analysis was performed on the subset of FAS population who were immune to dengue at baseline. Here, 'number of subjects analysed'=subjects evaluable for this end-point and ‘n’=subjects with available data for each specified category.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Pre-vaccination) and 28 days after the dose of Tdap vaccination
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Immediate Unsolicited Adverse Events (AE) Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||||||||
End point description |
An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the electronic case report form (eCRF) in terms of diagnosis and/or onset post-vaccination. Any unsolicited systemic AE occurred during first 30 minutes post-vaccination was recorded on the CRF as immediate AE. At Visit 1, subjects of Group 1 received no vaccination and subjects of Group 2 received only Tdap vaccination. At Visit 2, subjects of Group 1 received both CYD and Tdap vaccination and subjects of Group 2 received only CYD vaccination. At Visit 4, subjects of Groups 1 and 2 received CYD vaccination. Analysis was performed on safety analysis set (SafAS) population, which included subjects who received at least one dose of the study vaccines (CYD and Tdap). Here, ‘n’=subjects with available data for each specified category and '99999' was used as a space filler which signifies that the subjects of Group 1 did not receive any vaccination at Visit 1 and therefore were not evaluable.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 30 minutes after any and each vaccination
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Solicited Injection Site Reactions Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A solicited reaction was an AE observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reactions included pain, erythema, and swelling. At Visit 1, subjects of Group 1 received no vaccination and subjects of Group 2 received only Tdap vaccination. At Visit 2, subjects of Group 1 received both CYD and Tdap vaccinations and subjects of Group 2 received only CYD vaccination. At Visit 4, subjects of Groups 1 and 2 received only CYD vaccination. Analysis was performed on SafAS population. Here, ‘n’=subjects with available data for each specified category. Here, '99999' was used as a space filler which signifies that the Group 1 subjects did not receive any vaccination at Visit 1 and therefore were not evaluable.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Within 7 days after any and each vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Solicited Systemic Reactions Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A solicited reaction was an adverse reaction observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited injection site reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1, subjects of Group 1 received no vaccination and subjects of Group 2 received only Tdap vaccination. At Visit 2, subjects of Group 1 received both CYD and Tdap vaccinations and subjects of Group 2 received only CYD vaccination. At Visit 4, subjects of Groups 1 and 2 received only CYD vaccination. Analysis was performed on SafAS population. Here, ‘n’=subjects with available data for each specified category. Here, '99999' was used as space filler which signifies that Group 1 subjects did not receive any vaccination at Visit 1 and were not evaluable.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Within 14 days after any and each vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||||||||
End point description |
An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination. At Visit 1, subjects of Group 1 received no vaccination and subjects of Group 2 received only Tdap vaccination. At Visit 2, subjects of Group 1 received both CYD and Tdap vaccinations and subjects of Group 2 received only CYD vaccination. At Visit 4, subjects of Groups 1 and 2 received CYD vaccination. Analysis was performed on SafAS population. Here, ‘n’=subjects with available data for each specified category and '99999' was used as a space filler which signifies that the subjects from Group 1 did not receive any vaccination at Visit 1 and therefore were not evaluable.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 28 days after any and each vaccination
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||||||||
End point description |
AESIs were AEs that are considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1, subjects of Group 1 received no vaccination and subjects of Group 2 received only Tdap vaccination. At Visit 2, subjects of Group 1 received both CYD and Tdap vaccinations and subjects of Group 2 received only CYD vaccination. At Visit 4, subjects of Groups 1 and 2 received CYD vaccination. Analysis was performed on SafAS population. Here, ‘n’=subjects with available data for each specified category and '99999' was used as a space filler which signifies that the subjects from Group 1 did not receive any vaccination at Visit 1 and therefore were not evaluable.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Within 7 days post any and each vaccination
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of Subjects Reporting Serious Adverse Events (SAEs) Including Serious AESIs Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||||||||
End point description |
SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; required hospitalisation or prolonged existing hospitalisation; persistent or significant disability/incapacity; congenital anomaly or a medically important event. AESIs were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. Analysis was performed on SafAS population.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From Day 0 up to 6 months after the last Tdap or CYD vaccination
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Subjects Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Tdap or CYD Dengue Vaccine | ||||||||||||
End point description |
Hospitalised suspected dengue case was defined as an acute febrile illness with diagnosis of dengue requiring hospitalisation (with bed attribution). In such cases, 1 unplanned acute blood sample (within the first 5 days after fever onset) was collected for virological confirmation of hospitalised suspected dengue case. A suspected case was considered VCD if there was a detection of wild type dengue virus by dengue non-structural protein 1 antigen ELISA and/or dengue reverse transcriptase-polymerase chain reactions. Analysis was performed on SafAS population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Day 0 up to 6 months after the last Tdap or CYD vaccination
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
AE data were collected from Day 0 up to Day 28 post any vaccination. SR data were collected from Day 0 up to Day 14 post-vaccination. The SAEs were collected throughout the trial, i.e. 6 months after last Tdap or CYD vaccination.
|
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Adverse event reporting additional description |
SR was an AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF (i.e., solicited) in terms of symptom and/or onset post-vaccination. Analysis was performed on SafAS population.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
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Reporting groups
|
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Reporting group title |
CYD Dengue Vaccine + Tdap vaccine (Concomitant Administration)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
Due to absence of response of competent authorities from The Philippines on the protocol amendment, the study was prematurely terminated before injection of last dose (3rd dose) of CYD dengue vaccine. Objectives related to 3rd dose was not assessed. |