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Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01373281
First received: June 8, 2011
Last updated: March 24, 2016
Last verified: March 2016
  Purpose

The aim of this trial is to assess the efficacy of the CYD dengue vaccine in preventing symptomatic, virologically-confirmed dengue cases.

Primary Objective:

To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic virologically-confirmed dengue cases, regardless of the severity, due to any of the four serotypes in children aged 2 to 14 years at the time of inclusion.

Secondary Objectives:

To describe the efficacy of CYD dengue vaccine after each dose in:

  • Preventing symptomatic virologically-confirmed dengue cases due to any of the four serotypes
  • Preventing symptomatic dengue cases, either virologically-confirmed or probable based on serological criteria, due to any of the four serotypes

To describe the occurrence of serious adverse events (SAEs), including serious adverse events of special interest in all subjects throughout the trial period.


Condition Intervention Phase
Dengue
Dengue Fever
Dengue Hemorrhagic Fever
Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus
Biological: Placebo: NaCl 0.9%
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Symptomatic Virologically Confirmed Dengue Cases (Vaccine Efficacy) Due to Any Serotype During the Active Phase Post-dose 3 Injection With CYD Dengue Vaccine [ Time Frame: 28 days and up to 13 months post-injection 3 ] [ Designated as safety issue: No ]

    Symptomatic virologically-confirmed dengue (VCD) cases were defined as acute febrile illness (temperature ≥38°C on at least 2 consecutive days) and confirmed by dengue reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. Cases defined as number of subjects with at least one symptomatic VCD episode from 28 days post-injection 3 to the end of Active Phase.

    The vaccine efficacy is considered as significant if the lower bound of its 95% CI (exact method by Breslow & Day) is greater than 25%.


  • The Person-years at Risk for Participants With Symptomatic Virologically Confirmed Dengue Cases (Vaccine Efficacy) Due to Any Serotype During the Active Phase Post-dose 3 Injection With CYD Dengue Vaccine [ Time Frame: 28 days and up to 14 months post-injection 3 ] [ Designated as safety issue: No ]
    The person-years at risk was the cumulative time (in years) until the participant was diagnosed with VCD or until the end of the active period, whichever came first. Data presented is the sum of individual units of time for which the participants contributed to the analyses. Incidence density was calculated as the number of VCD cases divided by the cumulative person-years at risk. The vaccine efficacy is considered as significant if the lower bound of its 95% CI (exact method by Breslow & Day) is greater than 25%.

  • Density Incidence of Symptomatic Virologically Confirmed Dengue Cases Due to Any Serotype During the Active Phase Post-dose 3 Injection With CYD Dengue Vaccine [ Time Frame: 28 days and up to 14 months post-injection 3 ] [ Designated as safety issue: No ]

    Symptomatic virologically-confirmed dengue (VCD) cases were defined as acute febrile illness (temperature ≥38°C on at least 2 consecutive days) and confirmed by dengue reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. Cases defined as number of subjects with at least one symptomatic VCD episode from 28 days post-injection 3 to the end of Active Phase.

    Density incidence: data are cases per 100 person-years at risk. Data presented is the sum of individual units of time for which the participants contributed to the analyses. Incidence density was calculated as the number of VCD cases divided by the cumulative person-years at risk.



Secondary Outcome Measures:
  • Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With CYD Dengue Tetravalent Vaccine [ Time Frame: Pre-vaccination 1 and Day 28 post each vaccination up to 25 months (visit 07) ] [ Designated as safety issue: No ]
    Geometric mean titers against each serotypes of the Dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) in a pre-defined subset of 2,000 subjects from each country (1,333 in the CYD Dengue Vaccine Group and 667 in the Control Group).

  • Percentage of Flavi Virus-Immuned Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine [ Time Frame: Pre-vaccination 1 and Day 28 post each vaccination up to 25 months (visit 07) ] [ Designated as safety issue: No ]
    Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) immune participants at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.

  • Percentage of Subjects With Solicited Injection-site and Systemic Reactions Following Any and Each Injection With CYD Dengue Tetravalent Vaccine [ Time Frame: Day 0 up to Day 14 post each vaccination ] [ Designated as safety issue: No ]
    Solicited injection-site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥50 mm. Grade 3 Solicited injection site reactions (12-14 years): Pain, Significant, prevents daily activity; Erythema and Swelling, >100 mm. Grade 3 Solicited injection site reactions: Fever, ≥39°C; Headache, Malaise, Myalgia, and Asthenia, Significant, prevents daily activity.


Enrollment: 10275
Study Start Date: June 2011
Estimated Study Completion Date: November 2017
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dengue Vaccine Group
Participants will receive CYD dengue vaccine at 0, 6, and 12 months
Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus
0.5 mL, Subcutaneous
Other Name: CYD Dengue Vaccine
Placebo Comparator: Control Group
Participants will receive a placebo vaccine at 0, 6, and 12 months
Biological: Placebo: NaCl 0.9%
0.5 mL, Subcutaneous

Detailed Description:

Participants will be randomized to either receive 3 injections of CYD dengue vaccine or a placebo at 0, 6, and 12 months.

A subset of participants from each country will also be evaluated for reactogenicity and immunogenicity to enable the generation of country-specific data on reactogenicity, immunogenicity, and baseline dengue and JE antibody levels.

  Eligibility

Ages Eligible for Study:   2 Years to 14 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 2 to 14 years on the day of inclusion and resident of the site zone
  • Subject in good health, based on medical history and physical examination
  • Assent form or informed consent form has been signed and dated by the subject (based on local regulations), and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations)
  • Subject able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria:
  • Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).
  • Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
  • Planned participation in another clinical trial during the present trial period
  • Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
  • Self-reported seropositivity for Human Immunodeficiency Virus (HIV) infection
  • Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
  • Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
  • Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
  • Planned receipt of any vaccine in the 4 weeks following any trial vaccination
  • Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily
  • Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
  • Identified as a site employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member (i.e., immediate, husband, wife and their children, adopted or natural) of the site employees or the Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373281

Locations
Indonesia
Denpasar, Bali, Indonesia, 80114
Bandung, West Java, Indonesia, 40161
Jakarta, Indonesia, 10430
Malaysia
Kuala Lumpur, Malaysia, 50586
Penang, Malaysia, 10450
Philippines
Cebu City, Philippines, 6000
San Pablo City, Philippines
Thailand
Muang District, Kamphaeng Phet Province, Thailand, 6200
Ban Pong Districts, Ratchaburi Province, Thailand, 70110
Photharam Districts, Ratchaburi Province, Thailand, 70120
Vietnam
Long Xuyen City, An Giang Province, Vietnam
My Tho City, Tien Giang Province, Vietnam
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur SA
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01373281     History of Changes
Other Study ID Numbers: CYD14  UTN: U1111-1116-4957 
Study First Received: June 8, 2011
Results First Received: September 15, 2015
Last Updated: March 24, 2016
Health Authority: United States: Food and Drug Administration
Philippines: Department of Health
Malaysia: Ministry of Health
Indonesia: National Agency of Drug and Food Control
Vietnam: Ministry of Health

Keywords provided by Sanofi:
Dengue
Dengue fever
Dengue Hemorrhagic Fever
CYD dengue vaccine
Flavivirus

Additional relevant MeSH terms:
Fever
Dengue
Hemorrhagic Fevers, Viral
Severe Dengue
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 05, 2016