Study of a Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 11 Years in Malaysia

Safety and Immunogenicity of a Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 11 Years in Malaysia

The purpose of this study was to evaluate the safety and immunogenicity of Phase III lots of the CYD dengue vaccine in a pediatric population in Malaysia.

Primary Objectives:

• To describe the safety (in terms of solicited and unsolicited adverse events) of the CYD dengue vaccine in all participants after each injection.
• To describe the antibody response to each dengue virus serotype post-injection 2 and post-injection 3.

Study Overview

• Status: Completed
• Conditions: Dengue Fever; Dengue Hemorrhagic Fever
• Intervention / Treatment: Biological: Live, attenuated, recombinant dengue serotypes 1, 2, 3, and 4 virus; Biological: Placebo: NaCl 0.9%

Detailed Description

Healthy participants aged 2 to 11 years received 3 vaccinations at pre-determined schedules and were followed-up for at least 6 months after the last vaccination.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Ipoh, Perak, Malaysia, 30990
  • Kuala Lumpur, Malaysia, 59100
  • Kuching, Sarawak, Malaysia, 93586
  • Negeri Sembilan, Malaysia, 70300

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 2 to 11 years on the day of inclusion
• Assent form was signed and dated by the participant (for participants ≥ 7 years) and informed consent form was signed and dated by the parent(s) or another legally accepted representative, and by an independent witness if the two parents or legally accepted representative were illiterate
• Participant and parent/legally accepted representative were able to attend all scheduled visits to comply with all trial procedures
• Participants in good health, based on medical history and physical examination
• For a female participant of childbearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, until at least 4 weeks after the last vaccination

Exclusion Criteria:

• Known pregnancy, or a positive urine pregnancy test (for female participant of child-bearing potential only)
• Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination
• Planned participation in another clinical trial during the present trial period
• Planned receipt of any vaccine in the 4 weeks following the trial first vaccination, except for pandemic influenza vaccination
• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
• Known 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 corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Seropositivity for human immunodeficiency virus (HIV) reported by the parent/legally acceptable representative
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion
• Participants who plan to move to another country/region within the 18 coming months
• Identified as a child (adopted or natural) of the Investigator or of site employees 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYD Dengue vaccine group; Participants received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months.	Biological: Live, attenuated, recombinant dengue serotypes 1, 2, 3, and 4 virus; 0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension; Other Names: CYD Dengue vaccine
Placebo Comparator: Placebo Group; Participants received 3 injections of placebo, 1 injection each at 0, 6, and 12 months.	Biological: Placebo: NaCl 0.9%; 0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo	Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions: Pain: Incapacitating, unable to perform usual activities; Erythema and Swelling: >=50 millimeter (mm). Grade 3 Solicited systemic reactions: Fever: >=39°Degree Celsius (C); Headache, Malaise, Myalgia, and Asthenia: Significant: Prevents daily activity.	Day 0 up to Day 14 post-any and each vaccination
Percentage of Flavivirus-Immune Participants Reporting Solicited Injection Site and Systemic Reactions Following Each Vaccination With CYD Dengue Vaccine or Placebo Vaccine	Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype with parental dengue virus strains (serotype 1, 2, 3, and 4) in the baseline sample.	Day 0 up to Day 14 post-each vaccination
Percentage of Flavivirus-Naïve Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Vaccination With CYD Dengue Vaccine or a Placebo Vaccine	Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Flavivirus-Naive participants were defined as participants without quantified antibodies against Japanese encephalitis and without antibody quantified against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample.	Day 0 up to Day 14 post-each vaccination
Percentage of Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each dengue serotype (1,2, 3 and 4) and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).	Pre-Injection 1 and Post-Injections 2 and 3
Percentage of Participants With Seropositivity Against at Least One, Two, Three, or the Four Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each dengue serotype (1, 2, 3, and 4) and was assessed using the dengue PRNT.	Pre-Injection 1 and Post-Injections 2 and 3
Geometric Mean Titers (GMTs) Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the dengue PRNT.	Pre-Injection 1 and Post-Injections 2 and 3
Percentage of Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo: Flavivirus-Immune Participants	Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each serotype (1, 2, 3, and 4) and was assessed using the Dengue PRNT. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample.	Pre-Injection 1 and Post-Injections 2 and 3
Percentage of Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo: Flavivirus-Naive Participants	Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each serotype (1, 2, 3, and 4) and was assessed using the Dengue PRNT. Flavivirus naïve participants were defined as participants without quantified antibodies against Japanese encephalitis and without quantified antibodies against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample.	Pre-Injection 1 and Post-Injections 2 and 3
GMTs of Flavivirus-Immune Participants Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the Dengue PRNT. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample.	Pre-Injection 1 and Post-Injections 2 and 3
GMT of Flavivirus-Naïve Participants Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the Dengue PRNT. Flavivirus-Naive participants were defined as participants without quantified antibodies against Japanese encephalitis and without antibody quantified against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample.	Pre-Injection 1 and Post- Injections 2 and 3

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Medical Director, Sanofi Pasteur Singapore

Publications and helpful links

General Publications

• Hss AS, Koh MT, Tan KK, Chan LG, Zhou L, Bouckenooghe A, Crevat D, Hutagalung Y. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study. Vaccine. 2013 Dec 2;31(49):5814-21. doi: 10.1016/j.vaccine.2013.10.013. Epub 2013 Oct 14.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2010
• Primary Completion (Actual): September 28, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Dengue fever; CYD dengue vaccine; Dengue hemorrhagic fever
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Wounds and Injuries; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Hemorrhagic Fevers, Viral; Dengue; Severe Dengue; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CYD32; UTN: U1111-1115-6579 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org