Clinical Trial Results:
Safety of ChimeriVax™ Dengue Tetravalent Vaccine in Subjects Aged 2 to 45 Years in Mexico
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Summary
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EudraCT number |
2014-001706-17 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
27 Aug 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Feb 2016
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First version publication date |
22 Jul 2015
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Other versions |
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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 |
CYD06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Sanofi Pasteur SA
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Sponsor organisation address |
2, avenue Pont Pasteur, Lyon cedex 07, France, F-69367
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Public contact |
Director, Clinical Development, Sanofi Pasteur SA, 33 (0)437 65 60 60, remi.forrat@sanofipasteur.com
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Scientific contact |
Director, Clinical Development, Sanofi Pasteur SA, 33 (0)437 65 60 60, remi.forrat@sanofipasteur.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001201-PIP01-11 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Feb 2008
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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 |
27 Aug 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
- To describe the safety of each injection of ChimeriVax™ Dengue Tetravalent Vaccine in four age groups of subjects: adults (18 to 45), adolescents (12 to 17), children (6 to 11), and children (2 to 5).
- To describe viremia after each injection of ChimeriVax™ Dengue Tetravalent Vaccine in the four age groups of subjects.
- To describe the humoral immune response against dengue before injection, and after each injection of ChimeriVax™ Dengue Tetravalent Vaccine in the four age groups of subjects.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. 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 |
Not applicable | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jan 2006
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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 |
Mexico: 126
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Worldwide total number of subjects |
126
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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) |
72
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Adolescents (12-17 years) |
36
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Adults (18-64 years) |
18
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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 02 February 2006 to 23 July 2007 at 2 clinical centers in Mexico. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 126 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Blinding implementation details |
The blind observer method was used for the first vaccination. The delegate study personnel(s)/pharmacist, independent of the safety evaluation and other evaluations, prepared and administered the vaccine. The subjects, Investigator or designated study personnel in charge of safety assessment did not know which treatment or product being administered. Labels on the secondary packaging were also designed to prevent the treatment from being identified.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Study Group 1 | |||||||||||||||||||||||||||
Arm description |
Subjects who received Sanofi Pasteur’s ChimeriVax™ Dengue Tetravalent Vaccine (serotypes 1, 2, 3, and 4) as first, second, and third injections on Day 0, Day 0 + 3.5 months, and Day 0 + 12 months. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
ChimeriVax Dengue Tetravalent Vaccine
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Investigational medicinal product code |
323
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL dose, subcutaneous, administered on Day 0 (1st injection), Day 0 + 3.5 months (2nd injection), and Day 0 + 12 months (3rd injection).
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Arm title
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Study Group 2 | |||||||||||||||||||||||||||
Arm description |
Subjects received Stamaril Pasteur® (Yellow Fever vaccine) as first injection on Day 0 and sanofi pasteur’s CYD Dengue vaccine (serotypes 1, 2, 3, and 4) as second injection (Day 0 + 3.5 months ) and third injection (Day 0 + 12 months). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
ChimeriVax Dengue Tetravalent Vaccine
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Investigational medicinal product code |
323
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL dose, subcutaneous, administered on Day 0 (1st injection), Day 0 + 3.5 months (2nd injection), and Day 0 + 12 months (3rd injection).
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Investigational medicinal product name |
Sanofi Pasteur live attenuated YF vaccine (Stamaril Pasteur®)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injection into the deltoid region on Day 0 as the first injection
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Baseline characteristics reporting groups
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Reporting group title |
Study Group 1
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Reporting group description |
Subjects who received Sanofi Pasteur’s ChimeriVax™ Dengue Tetravalent Vaccine (serotypes 1, 2, 3, and 4) as first, second, and third injections on Day 0, Day 0 + 3.5 months, and Day 0 + 12 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Study Group 2
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Reporting group description |
Subjects received Stamaril Pasteur® (Yellow Fever vaccine) as first injection on Day 0 and sanofi pasteur’s CYD Dengue vaccine (serotypes 1, 2, 3, and 4) as second injection (Day 0 + 3.5 months ) and third injection (Day 0 + 12 months). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Study Group 1
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Reporting group description |
Subjects who received Sanofi Pasteur’s ChimeriVax™ Dengue Tetravalent Vaccine (serotypes 1, 2, 3, and 4) as first, second, and third injections on Day 0, Day 0 + 3.5 months, and Day 0 + 12 months. | ||
Reporting group title |
Study Group 2
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Reporting group description |
Subjects received Stamaril Pasteur® (Yellow Fever vaccine) as first injection on Day 0 and sanofi pasteur’s CYD Dengue vaccine (serotypes 1, 2, 3, and 4) as second injection (Day 0 + 3.5 months ) and third injection (Day 0 + 12 months). | ||
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End point title |
Number of Subjects Reporting a Solicited Injection-site or Systemic Reactions Following the First Vaccination with Sanofi Pasteur's CYD Dengue Vaccine or Yellow Fever Vaccine (Stamaril Pasteur®) [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site: Pain, Erythema, and Edema. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection site reactions: Pain – Incapacitating, unable to perform usual activities; Erythema and Edema - ≥5 cm. Grade 3 Solicited systemic reactions: Fever - ≥39˚C axillary; Headache, Malaise, Myalgia, and Asthenia – Prevents daily activity.
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 14 post-first vaccination
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects Reporting a Solicited Injection-site or Systemic Reactions Following the Second Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site: Pain, Erythema, and Edema. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection site reactions: Pain – Incapacitating, unable to perform usual activities; Erythema and Edema - ≥5 cm. Grade 3 Solicited systemic reactions: Fever - ≥39˚C axillary; Headache, Malaise, Myalgia, and Asthenia – Prevents daily activity.
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End point type |
Primary
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End point timeframe |
Day 0 to Day 14 post-second vaccination
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects Reporting a Solicited Injection-site or Systemic Reactions Following the Third Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site: Pain, Erythema, and Edema. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection site reactions: Pain – Incapacitating, unable to perform usual activities; Erythema and Edema - ≥5 cm. Grade 3 Solicited systemic reactions: Fever - ≥39˚C axillary; Headache, Malaise, Myalgia, and Asthenia – Prevents daily activity.
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End point type |
Primary
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End point timeframe |
Day 0 to Day 14 post-third vaccination
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Non-serotype Specific CYD Viremia by Flavivirus Reverse Transcriptase Polymerase Chain Reaction After the First Vaccination with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) [4] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
CYD Dengue vaccine and Yellow Fever vaccine virus were assessed using the flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR).
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End point type |
Primary
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End point timeframe |
Day 0 (V01; pre-vaccination) and Day 7 (V01+7) and Day 14 (V01+14) post-first vaccination
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Non-serotype Specific CYD Viremia by Flavivirus Reverse Transcriptase-Polymerase Chain Reaction After the Second Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [5] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
CYD Dengue Vaccine and Yellow Fever vaccine antibodies were assessed using the flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR).
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End point type |
Primary
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End point timeframe |
Day 0 (V06; pre-second vaccination) and Day 7 (V06+7) and Day 14 (V06+14) post-second vaccination
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Non-serotype Specific CYD Viremia by Yellow Fever Flavivirus Reverse Transcriptase-Polymerase Chain Reaction After the Second Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [6] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibodies to CYD Dengue vaccine and Yellow Fever vaccine antigens were assessed using the Yellow Fever Flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR).
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End point type |
Primary
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End point timeframe |
Day 0 (V06; pre-second vaccination) and Day 7 (V06+7) and Day 14 (V06+14) post-second vaccination
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Non-serotype Specific CYD Viremia by Flavivirus Reverse Transcriptase-Polymerase Chain Reaction After the Third Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [7] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibodies to CYD Dengue vaccine and Yellow Fever vaccine antigens were assessed using the Yellow Fever Flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR).
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End point type |
Primary
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End point timeframe |
Day 0 (V11; pre-third vaccination) and Day 7 (V11+7) post-third vaccination
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects with Non-serotype Specific CYD Viremia by Yellow Fever Reverse Transcriptase-Polymerase Chain Reaction After the Third Vaccination with Sanofi Pasteur's CYD Dengue Vaccine [8] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibodies to CYD Dengue vaccine and Yellow Fever vaccine antigens were assessed using the Yellow Fever Flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR).
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End point type |
Primary
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End point timeframe |
Day 0 (V11; pre-third vaccination) and Day 7 (V11+7) post-third vaccination
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Geometric Mean Titers of Neutralizing Antibodies Against Dengue Serotype Strain 1 Before and Following Each Injection with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against each of the four parental dengue virus serotype strains of ChimeriVax™ Dengue Tetravalent Vaccine constructs, and against the Thai Mahidol four dengue virus serotype strains were assessed by the Plaque Reduction Neutralization Test, (PRNT)
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first, second, and third vaccination) and Day 28 post-first, second, and third post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
P-value test comparing GMT pre- and post-injection | ||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
P-values for tests comparing GMTs after vaccinations between vaccine groups are adjusted on age groups. ANCOVA models performed on Log10 distributions after vaccinations adjusted on age groups and on Log10 distributions before vaccinations.
|
||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Study Group 1 v Study Group 2
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
126
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
other [9] | ||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
= 0.5656 [10] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [9] - Intra-group comparisons were assessed in pre-first, second, and third injection (inj.) vs. post-first, second, and third inj. [10] - Grp 1; Parental: Pre-each inj. vs. Post-each inj. was P=0.5656, 0.9408; and 0.5194, respectively. Mahidol: P=0.0723, 0.3274, and 0.2250. Grp 2; Parental: P=0.5656, 0.9408, 0.5194. Mahidol: P=0.0723, 0.3274, and 0.2250. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers of Neutralizing Antibodies Against Dengue Serotype Strain 2 Before and Following Each Injection with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against each of the four parental dengue virus serotype strains of ChimeriVax™ Dengue Tetravalent Vaccine constructs, and against the Thai Mahidol four dengue virus serotype strains were assessed by the Plaque Reduction Neutralization Test, (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first, second, and third vaccination) and Day 28 post-first, second, and third post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
P-value test comparing GMT pre- and post-injection | ||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
P-values for tests comparing GMTs after vaccinations between vaccine groups are adjusted on age groups. ANCOVA models performed on Log10 distributions after vaccinations adjusted on age groups and on Log10 distributions before vaccinations.
|
||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Study Group 1 v Study Group 2
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
126
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
other [11] | ||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
= 0.0003 [12] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [11] - Intra-group comparisons were assessed in pre-first, second, and third injection (inj.) vs. post-first, second, and third inj. [12] - Grp 1; Parental: Pre-each inj. vs. Post-each inj. was P=0.0003, 0.6049; and 0.8375, respectively. Mahidol: P=0.0033, 0.1651, and 0.0759. Grp 2; Parental: P=0.0003, 0.6049, 0.8375. Mahidol: P=0.0033, 0.1651, and 0.0759. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers of Neutralizing Antibodies Against Dengue Serotype Strain 3 Before and Following Each Injection with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against each of the four parental dengue virus serotype strains of ChimeriVax™Dengue Tetravalent Vaccine constructs and against the Thai Mahidol four dengue virus serotype strains were assessed using the Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first, second, and third vaccination) and Day 28 post-first, second, and third post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
P-value test comparing GMT pre- and post-injection | ||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
P-values for tests comparing GMTs after vaccinations between vaccine groups are adjusted on age groups. ANCOVA models performed on Log10 distributions after vaccinations adjusted on age groups and on Log10 distributions before vaccinations.
|
||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Study Group 1 v Study Group 2
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
126
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
other [13] | ||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [14] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [13] - Intra-group comparisons were assessed pre-first, second, and third injection (inj.) vs. post-first, second, and third inj. [14] - Grp 1; Parental: Pre-each inj. vs. Post-each inj. was P<0.0001, 0.2976; and 0.8712, respectively. Mahidol: P=0.0011, 0.5503, and 0.9928. Grp 2; Parental: P<0.0001, 0.2976, 0.8712. Mahidol: P=0.0011, 0.5503, and 0.9928. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers of Neutralizing Antibodies Against Yellow Fever Before and Following Vaccination with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) [15] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against Yellow Fever antigens were assessed using the Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first [V01] and second vaccination [V06]) and Day 28 post-first (V04) and second (V09) post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects with Antibody titer ≥ 10 (1/dil) Against Yellow Fever Antigen Before and Following Vaccination with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever Vaccine (Stamaril Pasteur®) [16] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against Yellow Fever antigens were assessed using the Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first [V01] and second vaccination [V06]) and Day 28 post-first (V04) and second (V09) post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Dengue Serotype Strain 4 Before and Following Each Injection with Sanofi Pasteur's CYD Dengue Vaccine and Yellow Fever (YF) vaccine (Stamaril Pasteur®) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against each of the four parental dengue virus serotype strains of ChimeriVax™ Dengue Tetravalent Vaccine constructs and against the Thai Mahidol four dengue virus serotype strains were assessed using the Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 (pre-first, second, and third vaccination) and Day 28 post-first, second, and third post-vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
P-value test comparing GMT pre- and post-injection | ||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
P-values for tests comparing GMTS after vaccinations between vaccine groups are adjusted on age groups. ANCOVA models performed on Log10 distributions after vaccinations adjusted on age groups and on Log10 distributions before vaccinations.
|
||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Study Group 1 v Study Group 2
|
||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
126
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
other [17] | ||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [18] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [17] - Intra-group comparisons were assessed in pre-first, second, and third injection (inj.) vs. post-first, second, and third inj. [18] - Grp 1; Parental: Pre-each inj. vs. Post-each inj. was P<0.0001, 0.0183, and 0.4596, respectively. Mahidol: P<0.0001, 0.0094, and 0.7019. Grp 2; Parental: P<0.0001, 0.0183, 0.4596. Mahidol: P<0.0001, 0.0094, and 0.7019. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events data were collected from Day 0 up to 28 days after each vaccination.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
7.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CYD TV/CYD TV
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects who received Sanofi Pasteur’s ChimeriVax™ dengue Tetravalent Vaccine (CYD TV; serotypes 1, 2, 3, and 4) as first, second, and third injections on Day 0, Day 0 + 3.5 months, and Day 0 + 12 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
YFV/CYD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Stamaril Pasteur® as first injection on Day 0 and sanofi pasteur’s CYD TV (serotypes 1, 2, 3, and 4) as second and third injections on Day 0 + 3.5 months and Day 0 + 12 months, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This was a solicited adverse event recorded in a diary card within 14 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This was a solicited adverse event recorded in a diary card within 14 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This was a solicited adverse event recorded in a diary card within 14 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This was a solicited adverse event recorded in a diary card within 14 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This was a solicited adverse event recorded in a diary card within 14 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
