Clinical trial NCT01374516: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America
Official title: Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue Fever
Dengue Hemorrhagic Fever
Dengue
Keywords: Dengue Virus
Dengue fever
Dengue Hemorrhagic Fever
CYD dengue vaccine
Flavivirus
Dengue Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-06-16
Enrollment: 20869
Sex: ALL
Minimum age (years): 9
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study was to assess the efficacy of Sanofi Pasteur's CYD dengue vaccine in preventing symptomatic virologically-confirmed dengue cases for dengue-endemic areas of Latin America.

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 (VCD) cases, regardless of the severity, due to any of the four serotypes in children and adolescents aged 9 to 16 years at the time of inclusion.

Secondary Objectives:

* To describe the efficacy of CYD dengue vaccine in preventing symptomatic VCD cases after the third dose to the end of the Active Phase, after at least 1 dose, and after 2 doses.
* To describe the occurrence of hospitalized VCD cases and the occurrence of severe (clinically severe or as per World Health Organization (WHO) criteria) VCD cases, throughout the Surveillance Expansion Period (SEP) and throughout the trial (from Day 0 until the end of the study).
* To describe the antibody response to each dengue serotype after Dose 2, after Dose 3, and 1 and 5 years after Dose 3.
* To describe the occurrence of serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period.

Detailed description: Participants were 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 (N=2000) was also evaluated for reactogenicity and immunogenicity.

For each participant, the Active Phase of dengue case detection began after the first injection (Dose 1) and continued until 13 months after the third injection (Dose 3). It was assumed that 12 months of surveillance should result in the detection of a sufficient number of VCD cases to allow for an assessment of efficacy.

The Hospital Phase began after the Active Phase. Participants with a febrile illness and requiring hospitalization were screened for dengue until the end of the study.

Participants who consented to participate in the SEP were actively followed for dengue case detection (i.e. at least weekly contact and capturing any acute febrile illness, not just hospitalized febrile cases, as in the Active Phase). The SEP was designed to maximize the detection of symptomatic VCD (hospitalized or not) in order to describe CYD dengue vaccine efficacy and safety in preventing symptomatic dengue in the long-term. Participants who declined participating in the SEP continued surveillance as in the Hospital Phase until trial completion.

Symptomatic VCD cases occurring more than (\>) 28 days after dose 3 (during the Active Phase) are defined as:

* Acute febrile illness (i.e. temperature \>=38 degree Celsius (°C) on at least 2 consecutive days)
* Virologically confirmed by dengue Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and/or dengue non-structural (NS)1 enzyme-linked immunosorbent assay (ELISA) Ag test.

Severity was assessed using a definition consistent with the 1997 WHO Classification Dengue Hemorrhagic Fever and by an independent Data Monitoring Committee (IDMC) severity criteria.

Eligibility criteria: Inclusion Criteria:

* Aged 9 to 16 years on the day of inclusion and resident of the site zone
* Participant in good health, based on medical history and physical examination
* Assent form or informed consent form has been signed and dated by the participant (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)
* Participant was able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

* Participant was 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 may interfere with the participant's 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.

Primary outcomes:
measure: Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: 28 days and up to 13 months post-injection 3
Secondary outcomes:
measure: Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 up to 13 months post-injection 3
measure: Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: 28 days post-injection 1 and up to 13 months post-injection 3
measure: Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: 28 days post-injection 2 and up to 13 months post-injection 3
measure: Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 to the end of study (up to 72 months)
measure: Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
measure: Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 up to the end of study (up to 72 months)
measure: Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)
measure: Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 to the end of study (up to 72 months)
measure: Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
measure: Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo
timeFrame: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3
measure: Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo
timeFrame: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3
measure: Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Within 7 days after each and any injection
measure: Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
timeFrame: Within 14 days after each and any injection
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
state: CE
city: Vitória
country: Brazil
state: ES
city: Goiania
country: Brazil
state: GO
city: Campo Grande
country: Brazil
state: MS
city: Natal
country: Brazil
state: RN
city: Aguazul
country: Colombia
state: Casanare
city: Yopal
country: Colombia
state: Casanare
city: Girardot
country: Colombia
state: Cundinamarca
city: Acacias
country: Colombia
state: Meta
city: Armenia
country: Colombia
state: Quindío
city: Calarcá
country: Colombia
state: Quindío
city: La Tebaida
country: Colombia
state: Quindío
city: Montenegro
country: Colombia
state: Quindío
city: Bucaramanga
country: Colombia
state: Santander
city: Tegucigalpa
country: Honduras
state: Municipalidad Del Distrito Central
city: Temixco
country: Mexico
state: Morelos
city: Municipio De Cd. Mante
country: Mexico
state: Tamaulipas
city: Veracruz Puerto
country: Mexico
state: Veracruz
city: Tizimin
country: Mexico
state: Yucatán
city: Valladolid
country: Mexico
state: Yucatán
city: Guayama
country: Puerto Rico
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
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