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

NCT01254422 | Completed Phase 3 Results DMC

• 2 other identifiers: CYD32UTN: U1111-1115-6579
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever

Keywords

Dengue fever; Dengue hemorrhagic fever; CYD dengue vaccine

Outcome Measures

Primary Outcomes (10)

• 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

Study Arms (2)

CYD Dengue vaccine group

EXPERIMENTAL

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

Placebo Group

PLACEBO COMPARATOR

Participants received 3 injections of placebo, 1 injection each at 0, 6, and 12 months.

Biological: Placebo: NaCl 0.9%

Interventions

Live, attenuated, recombinant dengue serotypes 1, 2, 3, and 4 virus BIOLOGICAL

0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension

Also known as: CYD Dengue vaccine

CYD Dengue vaccine group

Placebo: NaCl 0.9% BIOLOGICAL

0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension

Also known as: Saline

Placebo Group

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Unknown Facility

Ipoh, Perak, 30990, Malaysia

Location

Unknown Facility

Kuala Lumpur, 59100, Malaysia

Location

Unknown Facility

Kuching, Sarawak, 93586, Malaysia

Location

Unknown Facility

Negeri Sembilan, 70300, Malaysia

Location

Related Publications (1)

• 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.

  PMID: 24135573 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

None reported

Results Point of Contact

• Title: Director
• Organization: Sanofi Pasteur SA

Contact-US@sanofi.com

Study Officials

• Medical Director

  Sanofi Pasteur Singapore

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: December 6, 2010
• Study Start: December 2, 2010
• Primary Completion: September 28, 2012
• Study Completion: January 1, 2013
• Last Updated: March 25, 2022
• Results First Posted: July 29, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

MY (4)