Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America

NCT01187433 | Completed Phase 2 Results DMC

• 2 other identifiers: CYD30UTN: U1111-1111-6073
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to generate immunogenicity and safety data in preparation for efficacy studies in Latin America. Primary Objectives:

• To describe the immune response to dengue viruses before and after each vaccination with CYD dengue vaccine.
• To evaluate the safety of each vaccination with CYD dengue vaccine.

Conditions

Dengue; Dengue Hemorrhagic Fever

Keywords

Dengue; Dengue hemorrhagic fever; CYD Dengue Vaccines

Outcome Measures

Primary Outcomes (11)

• 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/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).

  Before and 28 days after each injection

• Percentage of Flavivirus Immune 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/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.

  Before and 28 days after each injection

• Percentage of Flavivirus Naïve Subjects 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/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.

  Before and 28 Days after each injection

• Percentage of Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).

  Before and 28 days after each injection

• Percentage of Flavivirus Immune Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.

  Before and 28 days after each injection

• Percentage of Flavivirus Naïve Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.

  Before and 28 days after each injection

• Geometric Mean Titer Ratios (GMTRs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Geometric mean titer ratios were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).

  Before and 28 days after each injection

• Geometric Mean Titers (GMTs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).

  Before and 28 days after each injection

• Geometric Mean Titers (GMTs) of Flavivirus Immune Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.

  Before and 28 days after each injection

• Geometric Mean Titer Ratios (GMTRs) of Flavivirus naïve Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo

  Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.

  Before and 28 days after each injection

• Percentage of Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo

  Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Injection-site reactions (9 to 11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Injection site reactions (≥12 years): Pain, Significant; prevents daily activity; Erythema and Swelling, \>10 cm. Grade 3 Systemic reactions: Fever, ≥39˚C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.

  Day 0 up to Day 14 post each vaccination

Study Arms (2)

Dengue Vaccine Group

EXPERIMENTAL

Participants will receive Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus vaccine

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

Control Group

PLACEBO COMPARATOR

Participants will receive a placebo, NaCl 0.9%.

Biological: NaCl 0.9%; Biological: Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed; Biological: Meningococcal A+C vaccine

Interventions

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

0.5 mL, Subcutaneous (SC)

Also known as: CYD Dengue Vaccine

Dengue Vaccine Group

NaCl 0.9% BIOLOGICAL

0.5 mL, Subcutaneous

Control Group

Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed BIOLOGICAL

0.5 mL, Intramuscular

Also known as: ADACEL®

Control Group

Meningococcal A+C vaccine BIOLOGICAL

0.5 mL, Intramuscular

Control Group

Eligibility Criteria

• Age: 9 Years - 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participant in good health, based on medical history and physical examination
• Provision of assent form/informed consent form signed by the participant and by the parent(s) or another legally acceptable representative
• Participant and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures
• For a female participant of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination until at least 4 weeks after the last vaccination

You may not qualify if:

• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia
• For a female participant of child-bearing potential, known pregnancy or positive urine pregnancy test at Visit 1
• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
• Breast-feeding woman
• Planned participation in another clinical trial during the present trial period
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy
• Known systemic hypersensitivity to any of the components of any of the trial vaccines or history of a life-threatening reaction to any of the trial vaccines or to a vaccine containing any of the same substances
• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator
• Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures
• Receipt of blood or blood-derived products in the preceding 3 months that might interfere with the assessment of immune response
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
• Planned receipt of any vaccine in the 4 weeks following the first trial vaccination
• Participant deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent
• Febrile illness (temperature ≥ 38.0 ºC) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment
• Severe diseases with or without fever, convulsions or neurological abnormalities without treatment or in progression.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Unknown Facility

Vitória, ES, 29040-091, Brazil

Location

Related Publications (2)

• Dayan GH, Garbes P, Noriega F, Izoton de Sadovsky AD, Rodrigues PM, Giuberti C, Dietze R. Immunogenicity and safety of a recombinant tetravalent dengue vaccine in children and adolescents ages 9-16 years in Brazil. Am J Trop Med Hyg. 2013 Dec;89(6):1058-1065. doi: 10.4269/ajtmh.13-0304. Epub 2013 Nov 4.

  PMID: 24189367 RESULT

• Coronel D, Garcia-Rivera EJ, Rivera DM, Arredondo-Garcia JL, Dietze R, Perroud AP, Cortes M, Bonaparte M, Wang H, Pagnon A, Jantet-Blaudez F, Penalosa LAR, Dayan G, Zambrano B, DiazGranados CA, Noriega F. Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial. Pediatr Infect Dis J. 2020 Oct;39(10):961-968. doi: 10.1097/INF.0000000000002830.

  PMID: 32932330 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Sodium Chloride; Tetanus Toxoid; adacel

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; Toxoids; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

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

RegistryContactUs@sanofipasteur.com

Study Officials

• Medical Director

  Sanofi Pasteur Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: August 20, 2010
• First Posted: August 24, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 21, 2022
• Results First Posted: November 11, 2016

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)