Study of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Subjects

Immunogenicity and Safety of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Viet Nam

This trial evaluated the use of a tetravalent vaccine against dengue.

Primary objectives:

• To describe the humoral immune response to dengue before and after each vaccination with tetravalent dengue vaccine in adults, adolescents, and children.
• To evaluate the safety of each vaccination with tetravalent dengue vaccine in the 4 age cohorts.
• To evaluate the persistence of antibodies against dengue during 5 years after the first vaccination with tetravalent dengue vaccine in the 4 age cohorts.

Study Overview

• Status: Completed
• Conditions: Dengue Fever; Dengue Hemorrhagic Fever; Dengue Virus; Dengue Disease
• Intervention / Treatment: Biological: CYD dengue vaccine serotypes (1, 2, 3, 4).; Biological: Meningococcal Polysaccharide A+C; NaCl; Typhoid Vi polysaccharide

Detailed Description

Safety assessments included solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • An Giang Province
    • Long Xuyên, An Giang Province, Vietnam
      • Sanofi Pasteur Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria :

• Aged 2 to 45 years on the day of inclusion.
• Provision of Informed Consent/Assent Form signed by the participant (and/or by the parent or another legally acceptable representative for participants <18 years).
• Participant (and parent/guardian for participants <18 years) 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 the first vaccination, until at least 4 weeks after the last vaccination.
• Participant in good health, based on medical history, physical examination and laboratory parameters.

Exclusion Criteria :

• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
• For a female participant of child-bearing potential, known pregnancy or positive serum pregnancy test at Screening.
• For a female participant of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of the first injection.
• Breast-feeding female participant.
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
• Human immunodeficiency virus, hepatitis B, or hepatitis C seropositivity in the blood sample taken at screening.
• Planned participation in another clinical trial during the first year of the study.
• 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 corticosteroids therapy.
• Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to 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 past 3 months that might interfere with the assessment of immune response.
• Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
• Laboratory abnormalities of at least moderate severity or clinically significant according to the Investigator in blood sample taken at screening.
• 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 receipt of any vaccine in the 4 weeks following the first trial vaccination.
• Familial atopy medical history (parents, brothers, or sisters).
• Previous vaccination with meningococcal A+C or typhoid vaccines within 3 years prior to inclusion.
• History of meningococcal or typhoid infections (confirmed either clinically, serologically or microbiologically).

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 who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Biological: CYD dengue vaccine serotypes (1, 2, 3, 4).; 0.5 mL, Subcutaneous; Other Names: ChimeriVax™
Sham Comparator: Control Vaccine Group; Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.	Biological: Meningococcal Polysaccharide A+C; NaCl; Typhoid Vi polysaccharide; Each at 0.5 mL, Subcutaneous, respectively; Other Names: NaCl; Meningococcal Polysaccharide Vaccine A+C; Typhim Vi®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain Before and Following Injection (Inj.) With CYD Dengue Tetravalent Vaccine	Geometric mean titers against each serotype of the parental dengue virus strains were assessed using the dengue Plaque Reduction Neutralization Test (PRNT).	Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3
Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain During the Follow-up Period	GMT against each serotype of the parental dengue virus strains were assessed using the dengue PRNT.	Year 1, Year 2, Year 3 and Year 4 after the Third Injection
Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine	Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.	Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3
Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine During the Follow-up Period	Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.	Year 1, Year 2, Year 3 and Year 4 after the Third Injection
Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine	Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain:- Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema and Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >= 5 cm.	7 days post-each injection
Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine	Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: >=37.5 degree Celsius (°C) to <=38.0°C, Grade 2: >38.0°C to <=39.0°C, Grade 3: >39.0°C. Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.	14 days post-each injection

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2009
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: April 2, 2009
• First Submitted That Met QC Criteria: April 2, 2009
• First Posted (Estimate): April 3, 2009

Study Record Updates

• Last Update Posted (Actual): April 5, 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 virus; Dengue fever; Dengue diseases; Dengue hemorrhagic fever; Dengue vaccine
• 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: CYD22; 2014-001709-41 (EudraCT Number)

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