Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Sanofi

Status and phase

Completed

Phase 3

Conditions

Dengue Hemorrhagic Fever

Dengue Fever

Dengue

Treatments

Biological: Placebo: (NaCl) 0.9% solution

Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus

Study type

Interventional

Funder types

Industry

Identifiers

NCT01374516

CYD15

UTN: U1111-1116-4986 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

20,869 patients

Sex

All

Ages

9 to 16 years old

Volunteers

Accepts Healthy Volunteers

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.