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

NCT01373281 | Completed Phase 3 Results DMC

• 3 other identifiers: CYD14UTN: U1111-1116-49572014-001708-24
• Study Type: interventional
• Target: 10,275
• Locations: 5 countries
• Sites: 12

Brief Summary

The aim of the trial was to assess the efficacy of the CYD dengue vaccine in preventing symptomatic, virologically-confirmed dengue (VCD) cases. Primary Objective: To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic VCD 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 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 serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period.
• To describe the occurrence of hospitalized virologically-confirmed dengue (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 to 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.

Conditions

Dengue; Dengue Fever; Dengue Hemorrhagic Fever

Keywords

Dengue; Dengue fever; Dengue Hemorrhagic Fever; CYD dengue vaccine; Flavivirus

Outcome Measures

Primary Outcomes (1)

• Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection (Inj.) With Either CYD Dengue Vaccine or a Placebo

  Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction and/or dengue NS protein 1 antigen enzyme-linked immunosorbent assay. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Vaccine Group.

  28 days and up to 13 months post-dose 3

Secondary Outcomes (13)

• Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo

  Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit 07) and 60 months (Visit 12) post-injection 3

• Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo

  Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3

• 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

  28 days post-injection 1 and up to 13 months post-injection 3

• Number of Symptomatic VCD Cases Due to Any Serotype 28 Days Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo

  28 days post-injection 2 and up to 13 months post-injection 3

• Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group

  Day 0 up to 13 months post-injection 3

Study Arms (2)

Dengue Vaccine Group

EXPERIMENTAL

Participants were to receive CYD dengue vaccine at 0, 6, and 12 months.

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

Control Group

PLACEBO COMPARATOR

Participants were to receive a placebo vaccine at 0, 6, and 12 months.

Biological: Placebo: Sodium chloride (NaCl) 0.9%

Interventions

Live, attenuated, dengue serotype 1, 2, 3, 4 virus BIOLOGICAL

0.5 mL, Subcutaneous

Also known as: CYD Dengue Vaccine

Dengue Vaccine Group

Placebo: Sodium chloride (NaCl) 0.9% BIOLOGICAL

0.5 mL, Subcutaneous

Control Group

Eligibility Criteria

• Age: 2 Years - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participant was 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 attended all scheduled visits and to comply with all trial procedures.

You may not qualify if:

• Participant was pregnant, or lactating, or was 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (12)

Unknown Facility

Denpasar, Bali, 80114, Indonesia

Location

Unknown Facility

Bandung, West Java, 40161, Indonesia

Location

Unknown Facility

Jakarta, 10430, Indonesia

Location

Unknown Facility

Kuala Lumpur, 50586, Malaysia

Location

Unknown Facility

Pulau Pinang, 10450, Malaysia

Location

Unknown Facility

Cebu City, 6000, Philippines

Location

Unknown Facility

San Pablo, 4000, Philippines

Location

Unknown Facility

Nai Muang, Changwat Kamphaeng Phet, 6200, Thailand

Location

Unknown Facility

Ban Pong, Changwat Ratchaburi, 70110, Thailand

Location

Unknown Facility

Photharam, Changwat Ratchaburi, 70120, Thailand

Location

Unknown Facility

Long Xuyen, An Giang, Vietnam

Location

Unknown Facility

Mỹ Tho, Tien Giang Province, Vietnam

Location

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MeSH Terms

Conditions

Dengue; Severe Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Medical Director
• Organization: Sanofi Pasteur Inc.

Contact-US@sanofi.com

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 14, 2011
• Study Start: June 3, 2011
• Primary Completion: August 1, 2014
• Study Completion: November 21, 2017
• Last Updated: March 21, 2022
• Results First Posted: November 16, 2015

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

MY (2); TH (3); VN (2); PH (2); ID (3)