Study of a Tetravalent Dengue Vaccine in Healthy Adults in Australia

Phase 3

Completed

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

• Registration Number: NCT01134263
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

The purpose of this study was to demonstrate that different CYD dengue vaccine lots manufactured using the same method and in the same location but at different times produce an equivalent immunological response after 3 doses.

Primary Objective

* To demonstrate that three different Phase III lots of CYD dengue vaccine induce an equivalent immune response in terms of post-Dose 3 geometric mean titers (GMTs) against the four parental serotypes.

Secondary Objectives:

* To demonstrate that data from one Phase II lot and pooled data from Phase III lots of CYD dengue vaccine show an equivalent immune response in terms of post-Dose 3 GMTs against the four parental serotypes.

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

Detailed Description

All participants received 3 doses of their assigned vaccine or placebo and provided blood samples at defined timepoints for flavivirus status and immunogenicity assessment. Safety data were collected in all participants after each dose and throughout the study.

Study Timeline

• Study First Submitted: 2010-05-27
• Study First Submitted QC: 2010-05-27
• Study First Posted: 2010-05-31
• Study Start: 2010-10-05
• Primary Completion: 2012-11
• Study Completion: 2013-02
• Status Verified: 2019-05
• Results First Submitted: 2019-05-21
• Results First Submitted QC: 2019-05-21
• Last Update Submitted: 2019-05-21
• Results First Posted: 2019-07-24
• Last Update Posted: 2019-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 715

Inclusion Criteria

• Aged 18 to 60 years on the day of inclusion.
• Informed consent form was signed and dated.
• Able to attend all scheduled visits and to comply with all trial procedures.
• For a woman of childbearing potential, use of an effective method of contraception, or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination (i.e., for 14 months).

Exclusion Criteria

• Known pregnancy, or a positive urine pregnancy test.
• History of flavivirus infection or vaccination or prolonged habitation in a dengue endemic area.
• Currently breastfeeding a child.
• 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, 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).
• Self-reported seropositivity for human immunodeficiency virus (HIV).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures.
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
• Identified as a site employee 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, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the site employees or the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CYD Dengue vaccine - Phase III Lot 3	Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus	Participants received 3 doses of CYD dengue vaccine (Phase III Lot 3) one each at Day 0 (vaccination 1), Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.
CYD Dengue vaccine - Phase III Lot 2	Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus	Participants received 3 doses of CYD dengue vaccine (Phase III Lot 2) one each at Day 0 (vaccination 1), Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.
CYD Dengue Vaccine Phase III Lot 1	Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus	Participants received 3 doses of CYD dengue vaccine (Phase III Lot 1), one each at Day 0 (vaccination 1),Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.
CYD Dengue vaccine - Phase II Lot	Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus	Participants received 3 doses of CYD dengue vaccine (Phase II Lot) one each at Day 0 (vaccination 1), Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.

Primary Outcome Measures

Name	Time	Method
Post-Dose 3 Geometric Mean Titers (GMTs) of Antibodies Against Each of the Four Dengue Virus Serotypes Following Vaccination With Phase III Lots of CYD Dengue Vaccine	28 days post-injection 3	GMTs against each of the 4 serotypes (serotype 1, serotype 2, serotype 3 and serotype 4) of dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) assay. The lot-to-lot consistency between 3 Phase III lots was based on the use of the two-sided 95% confidence interval (CI) of the differences of the means of the log10 transformed post-vaccination titers between pairs of lots.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers of Antibodies Against Each of the Four Dengue Virus Serotypes Following Vaccination With Pooled Phase III Lots (1, 2 or 3 )and Phase II Lot of CYD Dengue Vaccine	28 days post-Injection 3	GMTs against each of the 4 serotypes (serotype 1, serotype 2, serotype 3 and serotype 4) of dengue virus strains were assessed using PRNT assay. Equivalence of Phase III vaccine with Phase II vaccine was assessed by Bridging between Phase III and Phase II Lot of CYD Dengue Vaccine.
Number of Participants With Solicited Injection Site Reactions After Any Vaccination	7 days post any vaccination	Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 3: Significant; prevents daily activity. Erythema and Swelling: Grade 3: \> 10 cm. Participants with Injection Site Reactions of any Grade (1, 2 or 3) and grade 3 were reported.
Number of Participants With Solicited Systemic Reactions After Any Vaccination	14 days post any vaccination	Solicited systemic reactions: Asthenia, Fever, Headache, Malaise and Myalgia. Fever: Grade 3: \>=39.0°C (\>=102.1°F). Headache, malaise, myalgia and asthenia: Grade 3: significant; prevents daily activity. Participants with systemic reactions of any Grade (1, 2 or 3) and grade 3 were reported.