Clinical Trial Results:
Immunogenicity and Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Viet Nam
Summary
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EudraCT number |
2014-001709-41 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 Jul 2014
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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 |
CYD22
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00875524 | ||
WHO universal trial number (UTN) |
- | ||
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 |
Senior Director, Clinical Development, Sanofi Pasteur SA, +65 6431 2358, Anh.Wartel-Tram@sanofipasteur.com
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Scientific contact |
Senior Director, Clinical Development, Sanofi Pasteur SA, +65 6431 2358, Anh.Wartel-Tram@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 |
10 Nov 2014
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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 |
12 Jul 2014
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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 |
Humoral immune response to dengue before and after each vaccination with CYD dengue vaccine
Persistence of antibodies (Abs) against dengue during 5 years after the first vaccination with CYD dengue vaccine
Safety and reactogenicity
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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 |
14 Mar 2009
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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 |
Vietnam: 180
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Worldwide total number of subjects |
180
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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) |
120
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Adolescents (12-17 years) |
30
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Adults (18-64 years) |
30
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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 18 March 2009 to 01 July 2010 at 1 clinical center in Vietnam. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 180 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized. | ||||||||||||||||||||||||
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 first and second vaccinations were administered in a blind-observer manner. The third vaccination was planned to be administered in a single-blind manner; however, due to the cancellation of the statistical analysis after the second vaccination, the third vaccination was also administered in a blind-observer manner. To ensure the blind-observer design of the 3 vaccinations, the product was prepared in a separate room whether neither the Investigator nor subject had access.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Dengue Group | ||||||||||||||||||||||||
Arm description |
Subjects who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations. | ||||||||||||||||||||||||
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, 3 injections at Day 0, Day 0 + 6 months, and Day 0 + 12 months.
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Arm title
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Control group | ||||||||||||||||||||||||
Arm description |
Subjects who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations, respectively. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Meningococcal Polysaccharide Vaccine A+C
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for suspension for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mL, subcutaneous, 1 injection at Day 0.
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Investigational medicinal product name |
Placebo (NaCl containing human serum albumin)
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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, subcutaneoous, 1 injection at Day 0 + 6 months.
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Investigational medicinal product name |
Typhoid Vi polysaccharide vaccine (Typhim Vi Vaccine)
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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 |
0.5 mL, subcutaneous, 1 injection at Day 0 + 12 months.
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Baseline characteristics reporting groups
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Reporting group title |
Dengue Group
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Reporting group description |
Subjects who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Subjects who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations, respectively. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Dengue Group
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Reporting group description |
Subjects who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations. | ||
Reporting group title |
Control group
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Reporting group description |
Subjects who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations, respectively. |
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End point title |
Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype with the Parental Dengue Virus Strain Before and Following Injection with ChimeriVax™ Dengue Tetravalent Vaccine [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Geometric mean titers against each serotype of the Parental Dengue Virus strains were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
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End point type |
Primary
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End point timeframe |
Pre-dose 1, 2, and 3 and 28 days Post-dose 1, 2, and 3
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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 |
Percentage of Subjects with Antibody titers ≥ 10 (1/dil) Against Each Serotypes with the Parental Dengue Virus Strains Following Injection with ChimeriVax™ Dengue Tetravalent Vaccine [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neutralizing antibody levels against each serotype of the Parental Dengue Virus strains were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
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End point type |
Primary
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End point timeframe |
Pre-dose 1, 2, and 3 and 28 days Post-dose 1, 2, and 3
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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 |
Percentage of Subjects with Solicited Injection-site and Systemic Reactions Following Any and Each Injection with CYD Dengue Tetravalent Vaccine [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 solicited injection site reactions: Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 solicited systemic reactions: Fever, >39.0°C; Headache, Malaise, Myalgia, and Asthenia, Prevents daily activities.
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End point type |
Primary
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End point timeframe |
Day 0 up to Day 14 post-each 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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Adverse events information
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Timeframe for reporting adverse events |
Adverse event data were collected from Day 0 (post-vaccination) up to 6 months after the last vaccination.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Dengue Group
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Reporting group description |
Subjects who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Subjects who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) vaccinations, respectively. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 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 7 days after any 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 after any 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 after any 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 after any 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. |
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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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08 Apr 2008 |
Refined methods used for diagnosis of symptomatic dengue cases, implemented third vaccination blind-observer procedures, clarified exclusion criteria, deleted the fingerprint system for identification, modified the category designations of the intensity scales, avoided the use of the trade name ChimeriVax™, and aligned the informed consent form and assent form with the modifications of the protocol. |
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23 Jul 2008 |
Updated the protocol in response to comments from the Vietnamese Ministry of Health Ethic Committee and added the possibility to perform safety surveillance on the 4-year follow-up in all subjects with at least 1 dose of dengue vaccine, including subjects who discontinued for any reason, except those discontinued due to consent withdrawal. |
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04 Nov 2008 |
Changed the name of the Coordinating Investigator, identified the trial organization for laboratory analyses, and updated the planned trial calendar. |
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15 Jun 2009 |
Updated time period for assay analyses, updated information reviewed by the Safety Review Committee, revised and updated the inclusion and exclusion criteria, and modified follow-up phone call procedures. |
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10 Jun 2010 |
Replaced the Pan reverse transcriptase-polymerase chain reaction (RT-PCR) assay with the dengue screen RT-PCR and the microneutralization assay with the Dengue Plaque Reduction Neutralization Test (PRNT), and cancelled the post-dose 2 analysis of safety and immunogenicity. |
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17 Oct 2013 |
Changed the name of the Sponsor's responsible medical officer and regional clinical trial manager, added a database lock and interim analysis on follow-up unblinded data, updated the Institutional Review Board section regarding the Joint Research Ethics Committee, updated the pharmacovigilance email address, and exploratory analyses about natural booster infections were added. |
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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 |