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Study of a Tetravalent Dengue Vaccine in Healthy Adults in Australia

Primary Purpose

Dengue Fever, Dengue Hemorrhagic Fever

Status
Completed
Phase
Phase 3
Locations
Australia
Study Type
Interventional
Intervention
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Placebo: NaCl 0.9%
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue Fever focused on measuring Dengue Fever, Dengue Hemorrhagic Fever, CYD Dengue Vaccine, Lot Consistency

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

CYD Dengue Vaccine Phase III Lot 1

CYD Dengue vaccine - Phase III Lot 2

CYD Dengue vaccine - Phase III Lot 3

CYD Dengue vaccine - Phase II Lot

Placebo

Arm Description

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.

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.

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.

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.

Participants received placebo matched to CYD dengue vaccine, one each at Day 0 (vaccination 1), Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.

Outcomes

Primary Outcome Measures

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
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

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
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
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
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.

Full Information

First Posted
May 27, 2010
Last Updated
May 21, 2019
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT01134263
Brief Title
Study of a Tetravalent Dengue Vaccine in Healthy Adults in Australia
Official Title
Lot-to-Lot Consistency and Bridging Study of a Tetravalent Dengue Vaccine in Healthy Adults in Australia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
October 5, 2010 (Actual)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Fever, Dengue Hemorrhagic Fever
Keywords
Dengue Fever, Dengue Hemorrhagic Fever, CYD Dengue Vaccine, Lot Consistency

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
An observer-blind procedure was followed for the three injections with CYD dengue vaccine or placebo. Neither the observer, Investigator, Sponsor, nor the participant knew which product was administered.
Allocation
Randomized
Enrollment
715 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYD Dengue Vaccine Phase III Lot 1
Arm Type
Experimental
Arm Description
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.
Arm Title
CYD Dengue vaccine - Phase III Lot 2
Arm Type
Experimental
Arm Description
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.
Arm Title
CYD Dengue vaccine - Phase III Lot 3
Arm Type
Experimental
Arm Description
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.
Arm Title
CYD Dengue vaccine - Phase II Lot
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to CYD dengue vaccine, one each at Day 0 (vaccination 1), Month 6 (vaccination 2), and Month 12 (vaccination 3), subcutaneously.
Intervention Type
Biological
Intervention Name(s)
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Other Intervention Name(s)
CYD Dengue vaccine
Intervention Description
0.5 ml, Subcutaneous (SC)
Intervention Type
Biological
Intervention Name(s)
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Other Intervention Name(s)
CYD Dengue vaccine
Intervention Description
0.5 ml, SC
Intervention Type
Biological
Intervention Name(s)
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Other Intervention Name(s)
CYD Dengue vaccine
Intervention Description
0.5 ml, SC
Intervention Type
Biological
Intervention Name(s)
Live, attenuated, recombinant dengue serotypes 1, 2, 3, & 4 virus
Other Intervention Name(s)
CYD Dengue vaccine
Intervention Description
0.5 ml, Subcutaneous (SC)
Intervention Type
Biological
Intervention Name(s)
Placebo: NaCl 0.9%
Other Intervention Name(s)
NaCl
Intervention Description
0.5 ml, SC
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
28 days post-injection 3
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
28 days post-Injection 3
Title
Number of Participants With Solicited Injection Site Reactions After Any Vaccination
Description
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.
Time Frame
7 days post any vaccination
Title
Number of Participants With Solicited Systemic Reactions After Any Vaccination
Description
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.
Time Frame
14 days post any vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur Inc.
Official's Role
Study Director
Facility Information:
City
Adelaide
ZIP/Postal Code
SA 5000
Country
Australia
City
Carina Heights
ZIP/Postal Code
QLD 4152
Country
Australia
City
Enoggera
ZIP/Postal Code
QLD 4051
Country
Australia
City
Heidelberg
ZIP/Postal Code
VIC 3084
Country
Australia
City
Herston
ZIP/Postal Code
QLD 4006
Country
Australia
City
Herston
ZIP/Postal Code
QLD 4029
Country
Australia
City
Subiaco
ZIP/Postal Code
WA 6008
Country
Australia
City
Westmead
ZIP/Postal Code
NSW 2145
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
26279339
Citation
Torresi J, Heron LG, Qiao M, Marjason J, Chambonneau L, Bouckenooghe A, Boaz M, van der Vliet D, Wallace D, Hutagalung Y, Nissen MD, Richmond PC. Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study. Vaccine. 2015 Sep 22;33(39):5127-34. doi: 10.1016/j.vaccine.2015.08.008. Epub 2015 Aug 13.
Results Reference
result
PubMed Identifier
28968794
Citation
Torresi J, Richmond PC, Heron LG, Qiao M, Marjason J, Starr-Spires L, van der Vliet D, Jin J, Wartel TA, Bouckenooghe A. Replication and Excretion of the Live Attenuated Tetravalent Dengue Vaccine CYD-TDV in a Flavivirus-Naive Adult Population: Assessment of Vaccine Viremia and Virus Shedding. J Infect Dis. 2017 Oct 17;216(7):834-841. doi: 10.1093/infdis/jix314.
Results Reference
derived

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Study of a Tetravalent Dengue Vaccine in Healthy Adults in Australia

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