Study of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Subjects in Singapore

NCT00880893 | Completed Phase 2 Results DMC

• 2 other identifiers: CYD282014-001713-26
• Study Type: interventional
• Target: 1,198
• Locations: 1 country
• Sites: 5

Brief Summary

Primary Objectives:

• To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.
• To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.
• To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants. Secondary Objectives:
• To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Dengue Virus; Dengue Diseases

Keywords

Dengue virus; Dengue fever; Dengue Hemorrhagic fever; Dengue diseases; Sanofi Pasteur's CYD Dengue Vaccine

Outcome Measures

Primary Outcomes (7)

• Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo

  Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, \>=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: \>=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: \>10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, \>=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.

  Day 0 up to 14 days post-any and each injection

• Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo

  Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.

  Day 0 up to 14 days post-each injection

• Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo

  Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).

  Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3

• Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).

  Pre-Injection 1 and 28 days Post-Injection 3

• Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).

  Pre-Injection 1 and 28 days Post-Injection 3

• Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo

  GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.

  Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3

• GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine

  GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.

  Pre-Injection 1 and 28 days Post-Injection 3

Secondary Outcomes (15)

• Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

• Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

• Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

• Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

• Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo

  Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

Study Arms (2)

CYD Dengue Vaccine Group

EXPERIMENTAL

Participant's received the CYD Dengue Vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Biological: CYD Dengue vaccine

Placebo Group

SHAM COMPARATOR

All participants received a placebo at first vaccination (Month 0). Participants \<12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants \>= 12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

Biological: NaCl + influenza virus or hepatitis A vaccine

Interventions

CYD Dengue vaccine BIOLOGICAL

0.5 mL, Subcutaneous on Day 0, Months 6 and 12

Also known as: Sanofi Pasteur's CYD Dengue Vaccine

CYD Dengue Vaccine Group

NaCl + influenza virus or hepatitis A vaccine BIOLOGICAL

0.5 mL, Subcutaneous (Intramuscular - Hepatitis A)

Also known as: NaCl 0.9%, Vaxigrip®, Havrix® pediatric formulation

Placebo Group

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant in good health, based on medical history and physical examination.
• Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.
• Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
• For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 4 weeks after the last vaccination.

You may not qualify if:

• Febrile illness (temperature \>= 37.5°C) or moderate or severe acute illness/infection on the day of the first vaccination, according to Investigator judgment.
• Breast-feeding woman.
• Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
• Personal or family history of thymic pathology or myasthenia.
• Previous hepatitis A vaccination (for children only).
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroid therapy.
• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
• Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response.
• 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 18 coming months.
• 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 an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
• Current or past alcohol abuse or drug addiction that may interfere with the participants ability to comply with trial procedures.
• Participant who plans to move to another country within the 18 coming months.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (5)

Unknown Facility

Singapore, 119074, Singapore

Location

Unknown Facility

Singapore, 169608, Singapore

Location

Unknown Facility

Singapore, 229899, Singapore

Location

Unknown Facility

Singapore, 308433, Singapore

Location

Unknown Facility

Singapore, 529889, Singapore

Location

Related Publications (2)

• Harenberg A, Begue S, Mamessier A, Gimenez-Fourage S, Ching Seah C, Wei Liang A, Li Ng J, Yun Toh X, Archuleta S, Wilder-Smith A, Shek LP, Wartel-Tram A, Bouckenooghe A, Lang J, Crevat D, Caillet C, Guy B. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore. Hum Vaccin Immunother. 2013 Nov;9(11):2317-25. doi: 10.4161/hv.25562. Epub 2013 Jul 9.

  PMID: 23839107 RESULT

• Leo YS, Wilder-Smith A, Archuleta S, Shek LP, Chong CY, Leong HN, Low CY, Oh ML, Bouckenooghe A, Wartel TA, Crevat D. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore. Hum Vaccin Immunother. 2012 Sep;8(9):1259-71. doi: 10.4161/hv.21224. Epub 2012 Aug 16.

  PMID: 22894958 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Hepatitis A Vaccines; Sodium Chloride; vaxigrip

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)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Director
• Organization: Sanofi Pasteur

Contact-US@sanofi.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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An observer-design for the first vaccination and a single-blind design for the second and third vaccination were chosen to minimize the bias of the vaccine evaluation. The Investigator in charge of safety evaluation, the Sponsor, and the participants/parents did not know which vaccine was administrated at the first visit. For the second and third vaccinations, the participants/parents did not know which vaccine was administered.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2009
• First Posted: April 14, 2009
• Study Start: April 7, 2009
• Primary Completion: October 1, 2014
• Study Completion: October 14, 2014
• Last Updated: March 21, 2022
• Results First Posted: July 29, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

SG (5)