Clinical Trial Results:
Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America
Summary
|
|
EudraCT number |
2014-001715-39 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 May 2012
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
10 Feb 2016
|
First version publication date |
29 Jul 2015
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
CYD30
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01187433 | ||
WHO universal trial number (UTN) |
U1111-1111-6073 | ||
Sponsors
|
|||
Sponsor organisation name |
Sanofi Pasteur Inc
|
||
Sponsor organisation address |
1 Discovery Drive, Swiftwater, United States, 18370
|
||
Public contact |
Director, Clinical Development, Sanofi Pasteur Inc, 52 55 5484 4891, enrique.rivas@sanofipasteur.com
|
||
Scientific contact |
Director, Clinical Development, Sanofi Pasteur Inc, 52 55 5484 4891, enrique.rivas@sanofipasteur.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001201-PIP01-11 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
12 Oct 2012
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
15 May 2012
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
Humoral immune response to dengue before and after each vaccination with dengue vaccine
Safety and reactogenicity
|
||
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.
|
||
Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
20 Aug 2010
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Brazil: 150
|
||
Worldwide total number of subjects |
150
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
59
|
||
Adolescents (12-17 years) |
91
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
Study subjects were enrolled from 20 August 2010 to 8 December 2011 at 1 clinical site in Brazil. | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
A total of 150 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized. | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | ||||||||||||||||||
Blinding implementation details |
An observer-blind procedure was implemented for all three injections. The blind-observer Investigator, Sponsor, and subjects/parents did not know which vaccine was administered. To maintain the blind, the vaccinator prepared and administered the vaccine(s) in a separate room away from the blind-observer Investigator who was in charge of the assessment of safety.
|
||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
CYD Dengue vaccine group | ||||||||||||||||||
Arm description |
Subjects received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
CYD Dengue vaccine
|
||||||||||||||||||
Investigational medicinal product code |
323
|
||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Powder and solvent for suspension for injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
0.5 mL, subcutaneous, 1 injection each at 0, 6, and 12 months.
|
||||||||||||||||||
Arm title
|
Control group | ||||||||||||||||||
Arm description |
Subjects received 3 injections of placebo, 1 injection each at 0, 6, and 12 months. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo (NaCl 0.9%)
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
0.5 mL, subcutaneous, 1 injection each at 0, 6, and 12 months.
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CYD Dengue vaccine group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 3 injections of placebo, 1 injection each at 0, 6, and 12 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
CYD Dengue vaccine group
|
||
Reporting group description |
Subjects received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months. | ||
Reporting group title |
Control group
|
||
Reporting group description |
Subjects received 3 injections of placebo, 1 injection each at 0, 6, and 12 months. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Seropositivity Against Each Serotype with the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1,2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Flavivirus-immune Subjects With Seropositivity Against Each Serotype with the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Flavivirus-naïve Subjects With Seropositivity Against Each Serotype with the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Flavivirus-immune Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [5] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Flavivirus-naïve Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [6] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seropositivity was defined as subjects achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titer Ratios (GMTRs) Against Each Serotype with the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [7] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titer ratios of antibodies against the dengue virus serotypes were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers (GMTs) of Flavivirus-immune Subjects Against Each Serotype with the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [8] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers of antibodies against the dengue virus serotypes were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titer Ratios (GMTRs) of Flavivirus-naïve Subjects Against Each Serotype with the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [9] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titer ratios of antibodies against the dengue virus serotypes were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus-naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [9] - 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 Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo [10] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Injection site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Injection site reactions (9-11 yrs): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Injection site reactions (≥12 yrs): Pain, Significant; prevents daily activity; Erythema and Swelling, >10 cm. Grade 3 Systemic reactions: Fever, ≥39°C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 0 up to Day 14 post-any and each vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [10] - 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) Against Each Serotype with the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo [11] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers of antibodies against the dengue virus serotypes were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [11] - 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 |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were collected from Day 0 (post-vaccination) up to Day 14 post-Injection 3.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
CYD Dengue vaccine group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received 3 injections of placebo, 1 injection each at 0, 6, and 12 months. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 after any injection; 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 7 days after any injection; 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 7 days after any injection; 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 after any injection; 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 7 days after any injection; 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. [6] - 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 after any injection; 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. [7] - 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 after any injection; 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? Yes | |||
Date |
Amendment |
||
11 Sep 2009 |
Replaced Principal Investigators and Sponsor's Regional Clinical Trial Managers in Venezuela as well as updated the site name. |
||
15 Nov 2009 |
Revised trial dates, replaced the meningococcal A+C vaccine (in Brazil) or ADACEL (in Venezuela) as third vaccination by placebo injection, updated the "Product Logistics" section accordingly, clarified the minimum timeline between two febrile episodes to consider two separate episodes, replaced control products 2 and 3 with placebo, modified the inclusion and exclusion criteria, offered a licensed, commercial vaccine meningococcal A+C vaccine for Brazil and ADACEL for Brazil after the completion of the safety surveillance period, implemented a temperature monitoring card, adapted a second temporary contraindication in the context of future pandemic influenza vaccination campaigns, revised contraindications accordingly, modified the text describing blood collection, revised the text regarding the use of unused stored serum samples, added a full description of the enzyme-linked immunosorbent assay with all acute samples collected from suspected dengue cases having been tested with the wild-type dengue reverse transcriptase-polymerase chain reaction. |
||
31 Mar 2010 |
Updated the trial personnel (including the Principal Investigator in Brazil and Sanofi Pasteur personnel) |
||
22 Jul 2010 |
Reworded to confirm that it was a monocenter trial conducted in Brazil, updated number of enrolled subjects to 150 instead of 300, statistical methods were revised, updated the methodology to the dengue screen reverse transcriptase-polymerase chain reaction assay and dengue plaque reduction neutralization test. |
||
09 Feb 2011 |
Expanded the description of events to be reviewed by the Independent Data Monitoring Committee, increased the number of visits to 10, changed the last study contact to a clinic visit to allow for the optional administration of the vaccine, clarified subject benefits, quantity of blood drawn was no longer specified to give more flexibility due to differences in the amount of blood collected, added a description of the optional administration of the vaccine at the last study contact, reworded clinical supplies section, revised text in the assessment method section in addition to updating text to wild-type dengue reverse transcriptase-polymerase chain reaction for technical accuracy, modified the interim analysis and statistical methods, revised the immunogenicity methods, modified the description of the flavivirus serology, updated study violations, and reworded the description of the handling of missing data and outliers. |
||
20 Oct 2011 |
Updated the study design such that it clarified all three vaccinations were handled in the same way, updated personnel information on the cover page, updated the statistical analyses sections, updated text regarding the status of the phase II trials at the time of the writing of this amendment, updated the date and version number of the Investigator's Brochure, updated text regarding the current status of the clinical trials and current available document, replaced meningococcal A+C vaccine with influenza vaccine since meningococcal A+C vaccine was no longer licensed in Brazil, updated current information on Principal Investigator, updated text to delete the interim analysis after the second vaccination, modified the description of the yellow fever dengue plaque reduction neutralization test assay, updated the description of the Per Protocol Analysis Set, Full Analysis Set, and Safety Analysis Set, and revised the handling of missing data and outliers section to incorporate statistical standard text. |
||
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 | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/24189367 |