Clinical Trial Results:
Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril®) Administered Concomitantly with Tetravalent Dengue Vaccine in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru
Summary
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EudraCT number |
2014-001714-26 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
02 Sep 2013
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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 |
29 Jul 2015
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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 |
CYD29
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01436396 | ||
WHO universal trial number (UTN) |
U1111-1116-4913 | ||
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, 69367
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Public contact |
Director, Clinical Development, Sanofi Pasteur SA, 598 2710 3710 X109, betzana.zambrano@sanofipasteur.com
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Scientific contact |
Director, Clinical Development, Sanofi Pasteur SA, 598 2710 3710 X109, betzana.zambrano@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? |
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 |
25 Nov 2013
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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 |
02 Sep 2013
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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 demonstrate the non-inferiority of the immune response against Yellow Fever (YF) in Flavivirus (FV)-naïve subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to subjects receiving one dose of Stamaril vaccine concomitantly with placebo.
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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 |
Not applicable | ||
Actual start date of recruitment |
07 Sep 2011
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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 |
Peru: 320
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Country: Number of subjects enrolled |
Colombia: 467
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Worldwide total number of subjects |
787
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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) |
787
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 07 September 2011 to 08 March 2012 at 2 clinical sites (1 in Colombia and 1 in Peru). | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 792 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized; 787 subjects were vaccinated. | |||||||||||||||||||||||||||
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, Monitor, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
To ensure that objective safety data were obtained, the trial was designed using an observer-blind methodology since the products were visually different and may be recognized. For first trial vaccination (V01), the person who administered the injections knew which products were administered while neither the subject or parent nor the Investigator in charge of safety evaluation knew which products were administered.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | |||||||||||||||||||||||||||
Arm description |
Subjects received the Stamaril vaccine and the CYD dengue vaccine at enrollment (M0) at 12 to 13 months, measles, mumps, rubella (MMR) vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV//Hib) (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
CYD Dengue vaccine
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Investigational medicinal product code |
323
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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, subcutaneous in the deltoid region of the upper arm, 1 injection each at 0, 6, and 12 months.
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Investigational medicinal product name |
Yellow Fever vaccine (Stamaril®)
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Investigational medicinal product code |
105
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Other name |
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Pharmaceutical forms |
Powder and solvent for suspension for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous in the deltoid region of the upper arm, 1 injection at Month 0.
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Arm title
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Group 2 | |||||||||||||||||||||||||||
Arm description |
Subjects received the Stamaril vaccine and placebo at enrollment (M0) at 12 to 13 months of age, MMR vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, DTaP-IPV//Hib (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
CYD Dengue vaccine
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Investigational medicinal product code |
323
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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, subcutaneous in the deltoid region of the upper arm, 2 injections each at 6 and 12 months.
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Investigational medicinal product name |
Yellow Fever vaccine (Stamaril®)
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Investigational medicinal product code |
105
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Other name |
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Pharmaceutical forms |
Powder and solvent for suspension for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous in the deltoid region of the upper arm, 1 injection at Month 0.
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Investigational medicinal product name |
Placebo (NaCl)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous in the deltoid region of the upper arm, 1 injection at Month 0.
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Baseline characteristics reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Subjects received the Stamaril vaccine and the CYD dengue vaccine at enrollment (M0) at 12 to 13 months, measles, mumps, rubella (MMR) vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV//Hib) (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Subjects received the Stamaril vaccine and placebo at enrollment (M0) at 12 to 13 months of age, MMR vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, DTaP-IPV//Hib (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Subjects received the Stamaril vaccine and the CYD dengue vaccine at enrollment (M0) at 12 to 13 months, measles, mumps, rubella (MMR) vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV//Hib) (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. | ||
Reporting group title |
Group 2
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Reporting group description |
Subjects received the Stamaril vaccine and placebo at enrollment (M0) at 12 to 13 months of age, MMR vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (M1) at 13 to 14 months, CYD dengue vaccine (M6) at 18 to 19 months, DTaP-IPV//Hib (M7) at 19 to 20 months, CYD dengue vaccine (M12) at 24 to 25 months, and hepatitis A vaccine (M13) at 25 to 26 months. |
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End point title |
Percentage of Non-immune Subjects With Seroconversion Against Yellow Fever Antigen After Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo | |||||||||||||||
End point description |
Neutralizing antibodies against yellow fever (YF) were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies ≥10 (1/dil) in flavivirus non-immune subjects.
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End point type |
Primary
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End point timeframe |
28 days Post-Injection 1
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Statistical analysis title |
Non-inferiority (Group 1 - Group 2) | |||||||||||||||
Statistical analysis description |
Non-inferiority of YF seroconversion rate was assessed 28 days post-Stamaril/CYD dengue vaccine (Group 1) or post-Stamaril/placebo (Group 2).
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Comparison groups |
Group 1 v Group 2
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Number of subjects included in analysis |
595
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | |||||||||||||||
Method |
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Parameter type |
Difference in Grp 1 - Grp 2 (percentage) | |||||||||||||||
Point estimate |
0.334
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-0.976 | |||||||||||||||
upper limit |
1.87 | |||||||||||||||
Notes [1] - The non-inferiority will be demonstrated if the lower limit of the 95% CI is greater than -10. The difference in percentage of seroconversion rates between group 1 and 2 is based on the Wilson score (without continuity adjustment) 95% two-sided confidence intervals. |
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End point title |
Percentage of All Subjects With Seroconversion Against Yellow Fever Antigen After Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo | |||||||||||||||
End point description |
Neutralizing antibodies against yellow fever (YF) were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies ≥10 (1/dil) in subjects YF-seronegative at baseline or 4-fold increase from pre- to post-YF antibody titers in subjects YF-seropositive at baseline.
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End point type |
Secondary
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End point timeframe |
28 days Post-Injection 1
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Statistical analysis title |
Non-inferiority (Group 1 - Group 2) | |||||||||||||||
Statistical analysis description |
Non-inferiority of YF seroconversion rate was assessed 28 days post-Stamaril/CYD dengue vaccine (Group 1) or post-Stamaril/placebo (Group 2).
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Comparison groups |
Group 1 v Group 2
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Number of subjects included in analysis |
758
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | |||||||||||||||
Method |
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Parameter type |
Difference in Grp 1 - Grp 2 (percentage) | |||||||||||||||
Point estimate |
-1.06
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-2.81 | |||||||||||||||
upper limit |
0.383 | |||||||||||||||
Notes [2] - The non-inferiority will be demonstrated if the lower limit of the 95% CI is greater than -10. The difference in percentage of seroconversion rates between group 1 and 2 is based on the Wilson score (without continuity adjustment) 95% two-sided confidence intervals. |
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End point title |
Geometric Mean Titers (GMTs) of Yellow Fever Antibodies In All Subjects Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||
End point description |
Geometric mean titers against yellow fever (YF) were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injection 1
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titer Ratios (GMTRs) of Yellow Fever Antibodies In All Subjects Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | |||||||||||||||
End point description |
Geometric mean titer ratios against yellow fever (YF) were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injection 1
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No statistical analyses for this end point |
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End point title |
Percentage of All Subjects With Yellow Fever Antibody Titers of ≥10 (1/dil) Before and After Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo | ||||||||||||||||||
End point description |
Neutralizing antibodies against yellow fever (YF) were assessed using a YF virus plaque reduction neutralization test (YF PRNT50) assay. Seroconversion was defined as YF antibodies ≥10 (1/dil) regardless of the flavivirus status of subjects at baseline.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injection 1
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titers (GMTs) of Dengue Virus Antibodies Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titer Ratios (GMTRs) of Dengue Virus Antibodies Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titer ratios against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Antibody Titer ≥ 10 (1/dil) Against Each Serotype with the Parental Dengue Virus Strains After Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibodies against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seroconversion was defined as antibody titers ≥10 (1/dil) against each serotype with the parental dengue virus strains.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Antibody Titer ≥ 10 (1/dil) Against At Least 1, 2, 3, or 4 Serotypes with the Parental Dengue Virus Strains After Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibodies against at least 1, 2, 3, or 4 serotypes with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titers of Dengue Virus Antibodies of Flavivirus-immune Subjects Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines, Followed by CYD Dengue Vaccin | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Flavivirus-immune subjects at baseline were defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for YF virus.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titers of Dengue Virus Antibodies of Flavivirus-Naïve Subjects Following Vaccination With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Flavivirus-non-immune (naïve) subjects at baseline were defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for YF virus.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Percentage of Flavivirus-immune Subjects With Antibody Titer ≥ 10 (1/dil) Against Each Serotype with the Parental Dengue Virus Strains After Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibodies against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Flavivirus-immune subjects at baseline were defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for YF virus.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Percentage of Flavivirus-naïve Subjects With Antibody Titer ≥ 10 (1/dil) Against Each Serotype with the Parental Dengue Virus Strains After Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibodies against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Flavivirus-non-immune (naïve) subjects at baseline were defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for YF virus.
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End point type |
Secondary
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End point timeframe |
Pre-Injection 1 and Post-Injections 2 and 3
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Injection With Yellow Fever Vaccine Concomitantly with Either CYD Dengue Vaccine or a Placebo, Followed by CYD Dengue Vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost and Irritability. Grade 3 Solicited injection site reactions: Tenderness, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, ≥50 mm. Grade 3 Solicited systemic reactions: Fever, >39.5°C; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Drowsiness, Sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable.
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End point type |
Secondary
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End point timeframe |
Day 0 up to Day 14 post-Injection 3
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from Day 0 (post-vaccination) up to 6 months post-Injection 3.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.4
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Reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Subjects received the Stamaril vaccine and the first dose of the CYD dengue vaccine at enrollment (Month 0) at 12 to 13 months of age, measles, mumps, rubella (MMR) vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (Month 1) at 13 to 14 months of age, second dose of CYD dengue vaccine (Month 6) at 18 to 19 months of age, diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV//Hib) (Month 7) at 19 to 20 months of age, third dose of the CYD dengue vaccine (Month 12) at 24 to 25 months of age, and hepatitis A vaccine (Month 13) at 25 to 26 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Subjects received the Stamaril vaccine and placebo at enrollment (Month 0) at 12 to 13 months of age, measles, mumps, rubella (MMR) vaccine, pneumococcal conjugated vaccine, and hepatitis A vaccine (Month 1) at 13 to 14 months of age, first dose of CYD dengue vaccine (Month 6) at 18 to 19 months of age, diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenza type b (DTaP-IPV//Hib) (Month 7) at 19 to 20 months of age, second dose of the CYD dengue vaccine (Month 12) at 24 to 25 months of age, and hepatitis A vaccine (Month 13) at 25 to 26 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 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. [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 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. [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 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. [8] - 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. [9] - 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. [10] - 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. [11] - 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. [12] - 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. [13] - 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. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Sep 2011 |
The Bogoto site initially planned could not participate due to incompletion of certification with the regulatory process, Peru requested 2 doses of Hepatitis A vaccines should be offered instead of 1 to all subjects as a benefit and the 6-month follow up visit could be a home visit if needed, information regarding the composition and administration of products was reworded to provide more flexibility, minor updates, methodology updates, and process clarification were made, and minor administrative updates including the change of the Regional Director of Clinical Development and Regional Clinical Trial Manager were included. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/22863660 |