Study of a Tetravalent Dengue Vaccine in Healthy Adult Subjects Aged 18 to 45 Years in India

Phase 2

Completed

• Conditions: Dengue Fever; Dengue Hemorrhagic Fever; Dengue
• Interventions: Biological: Live, attenuated, recombinant dengue serotype 1, 2, 3, 4 virus

• Registration Number: NCT01550289
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

The aim of this study is to evaluate the immunogenicity and safety of the CYD dengue vaccine in India adult subjects.

Primary Objectives:

* To describe the neutralizing antibody response to each dengue virus serotype before the first vaccination and after each vaccination with CYD dengue vaccine in all subjects.

* To describe the safety of the CYD dengue vaccine after each dose in all subjects.

Secondary Objective:

* To detect symptomatic dengue cases occurring at any time in the trial.

Detailed Description

Participants will receive 3 doses of their randomized treatment (vaccine or placebo). Flavivirus status will be determined at baseline (before the first dose) and the vaccine immunogenicity assessment will be at 28 days after each vaccination. Reactogenicity data will be collected in all subjects after each dose. Serious adverse events and adverse events of special interest will be collected throughout the study.

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-03-07
• Study First Submitted QC: 2012-03-08
• Study First Posted: 2012-03-09
• Primary Completion: 2013-12
• Study Completion: 2014-02
• Results First Submitted: 2016-09-14
• Results First Submitted QC: 2016-09-14
• Results First Posted: 2016-11-03
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-15
• Last Update Posted: 2022-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

• Aged 18 to 45 years on the day of inclusion
• Informed consent form has been signed and dated by the subject (and by an independent witness, if applicable)
• Subject is able to attend all scheduled visits and to comply with all trial procedures
• Subject in good health, based on medical history and physical examination

Exclusion Criteria

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
• 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 any trial 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)
• Known seropositivity for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C reported by the subject
• 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, is at a stage where it might interfere with trial conduct or completion
• Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Identified as an Investigator or employee of the Investigator or study center, with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: CYD dengue vaccine	Live, attenuated, recombinant dengue serotype 1, 2, 3, 4 virus	Subjects will receive a dose of CYD dengue vaccine at 0, 6, and 12 months, respectively.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Antibody Titer ≥ 10 1/Dil Against at Least 1, 2, 3, or 4 Dengue Virus Serotypes Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT).
Summary of Geometric Mean Titer Ratios of Antibodies Against Each Dengue Serotype Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT).
Percentage of Participants With Antibody Titer ≥ 10 1/Dil Against Each Dengue Virus Serotype Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT).
Summary of Geometric Mean Titers of Antibodies Against Each Dengue Serotype Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT).
Percentage of Participants With Solicited Injection-site and Systemic Reactions After Any and Each Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo	Day 0 up to Day 14 post each injection	Solicited injection-site: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection site reactions: Pain Significant; prevents daily activities; Erythema and Swelling \>100 mm. Grade 3 Solicited systemic reactions: Fever ≥39.0˚C; Headache, Malaise, Myalgia, and Asthenia Significant; prevents daily activities.

Secondary Outcome Measures

Name	Time	Method
Percentage of Flavivirus-Immune Participants With Antibody Titer ≥ 10 1/Dil Against Each Dengue Serotype Before and After Each Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) immune participants at baseline are defined as those participants with ≥10 (1/dil) for at least one serotype with the parental dengue virus strain or for Japanese encephalitis (JE) virus.
Percentage of Flavivirus-non Immune Participants With Antibody Titer < 10 1/Dil Against Each Dengue Serotype Before and After Each Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) non-immune participants at baseline are defined as those participants with \<10 (1/dil) for all serotypes with parental dengue virus strains and for Japanese encephalitis (JE) virus.
Summary of Geometric Mean Titers of Antibodies Against Each Dengue Serotype In Flavivirus Non-immune Participants Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) non immune participants at baseline are defined as those participants with \<10 (1/dil) for all serotypes with parental dengue virus strains and for Japanese encephalitis (JE) virus.
Summary of Geometric Mean Titers of Antibodies Against Each Dengue Serotype In Flavivirus-Immune Participants Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) immune participants at baseline are defined as those participants with ≥10 (1/dil) for at least one serotype with the parental dengue virus strain or for Japanese encephalitis (JE) virus.
Percentage of Flavivirus-Immune Participants With Antibody Titer ≥ 10 1/Dil Against at Least 1, 2, 3, or 4 Dengue Serotypes Before and After Each Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) immune participants at baseline are defined as those participants with ≥10 (1/dil) for at least one serotype with the parental dengue virus strain or for Japanese encephalitis (JE) virus.
Percentage of Flavivirus-non Immune Participants With Antibody Titer < 10 1/Dil Against at Least 1, 2, 3, or 4 Dengue Serotypes Before and After Each Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) non immune participants at baseline are defined as those participants with \<10 (1/dil) for all serotypes with parental dengue virus strains and for Japanese encephalitis (JE) virus.
Summary of Geometric Mean Titer Ratios of Antibodies Against Each Dengue Serotype In Flavivirus Non-immune Participants Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) immune participants at baseline are defined as those participants with ≥10 (1/dil) for at least one serotype with the parental dengue virus strain or for Japanese encephalitis (JE) virus.
Summary of Geometric Mean Titer Ratios of Antibodies Against Each Dengue Serotype In Flavivirus-Immune Participants Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo	Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1)	Dengue neutralizing antibody levels were measured by dengue plaque reduction neutralization test (PRNT). Flavivirus (FV) immune participants at baseline are defined as those participants with ≥10 (1/dil) for at least one serotype with the parental dengue virus strain or for Japanese encephalitis (JE) virus.