Trial Review

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:30pm (AEST) on Thursday 31st July for website maintenance.

Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12625000742471
Ethics application status
Approved
Date submitted
27/06/2025
Date registered
15/07/2025
Date last updated
15/07/2025
Date data sharing statement initially provided
15/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding immune responses to the Yellow Fever (YF) and Japanese Encephalitis (JE) flavivirus vaccines (The FLAVIFLAV Study)
Scientific title
The effect of the order of Japanese Encephalitis and Yellow Fever vaccine administration on Yellow Fever vaccine protection in healthy adults.
Secondary ID [1] 314749 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Yellow Fever 337962 0
Japanese Encephalitis 337963 0
Condition category
Condition code
Infection 334280 334280 0 0
Other infectious diseases
Infection 334398 334398 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Yellow Fever (YF) vaccine and Japanese Encephalitis (JE) vaccine.
Participants will be randomised to the order in which they receive a YF vaccine and a JE vaccine (JE-YF or YF-JE vaccination arms), given 4 months apart.

YF vaccine - 0.5 mL single dose of reconstituted vaccine given by intramuscular or subcutaneous injection.

JE vaccine - 0.5 mL single dose of the reconstituted vaccine given by intramuscular injection to the deltoid region of the upper arm

Adherence to vaccine order will be monitored by audit of case report files and REDCap
Intervention code [1] 331352 0
Treatment: Drugs
Comparator / control treatment
The YF-JE arm is the control group
Control group
Active

Outcomes
Primary outcome [1] 341939 0
Yellow Fever virus genome copies in the Japanese Encephalitis vaccine-Yellow Fever vaccine group compared to the Yellow Fever-Japanese Encephalitis group
Timepoint [1] 341939 0
Day 5 post yellow fever vaccination
Secondary outcome [1] 449090 0
Area under the curve of the Yellow Fever virus genome copies for the Japanese Encephalitis vaccine-Yellow Fever vaccine group compared to the Yellow Fever-Japanese Encephalitis group
Timepoint [1] 449090 0
Days 3 and 7 post Yellow Fever vaccination
Secondary outcome [2] 449092 0
Japanese Encephalitis virus genome copies in the Japanese Encephalitis vaccine-Yellow Fever vaccine group compared to the Yellow Fever-Japanese Encephalitis group
Timepoint [2] 449092 0
Day 5 post Japanese Encephalitis vaccination
Secondary outcome [3] 449096 0
Area under the curve of the Japanese Encephalitis virus genome copies for the Japanese Encephalitis vaccine-Yellow Fever vaccine group compared to the Yellow Fever-Japanese Encephalitis group
Timepoint [3] 449096 0
Days 3 and 7 post Japanese Encephalitis vaccination
Secondary outcome [4] 449097 0
Change in Yellow Fever virus binding antibody titres in the Japanese Encephalitis vaccine-Yellow Fever vaccination group
Timepoint [4] 449097 0
Day 0 and 28 post-Yellow Fever vaccination
Secondary outcome [5] 449098 0
Change in Japanese Encephalitis virus binding antibody titres in the Japanese Encephalitis vaccine-Yellow Fever vaccination group
Timepoint [5] 449098 0
Day 0 and 28 post-Japanese Encephalitis vaccination
Secondary outcome [6] 449099 0
Reported adverse events in the Japanese Encephalitis vaccine-Yellow Fever vaccination group
Timepoint [6] 449099 0
Day 14 post-Japanese Encephalitis vaccination (Day 14 of study) and Day 14 post-Yellow Fever vaccination (Day 134 of study)
Secondary outcome [7] 449100 0
Reported adverse events in the Yellow Fever-Japanese Encephalitis group vaccination group
Timepoint [7] 449100 0
Day 14 post-Yellow Fever vaccination (Day 14 of study) and Day 14 post-Japanese Encephalitis vaccination (Day 134 of study)

Eligibility
Key inclusion criteria
Healthy adults:
•Aged 18-60 years
•Healthy with no significant immunosuppressive illnesses. These include but are not limited to:
-cancer or treatment of cancer or organ transplantation
-treatment of auto-immune or inflammatory conditions such as inflammatory arthritis or inflammatory bowel disease
-use of corticosteroid, TNF inhibitor, interleukins, interferons, cyclosporine or other immunosuppressive medications
-significant renal or liver disease
•Willing and available to have blood samples taken per the schedule of events
•Willing to receive YF vaccine and JE vaccine
•Willing to be randomly assigned to receive the vaccines 4 month apart in different order (either JE-YF or YF-JE)
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
•prior YF disease or vaccination
•prior JE disease or vaccination
•Symptomatic HIV infection or asymptomatic HIV with impaired immune function (CD4 T-cell count <200 cells/mm3
•history of thymus dysfunction (including myasthenia gravis, thymoma or thymectomy (for any reasons).
•a history of severe allergic reaction to eggs or chicken proteins
•Pregnant or breastfeeding women and women planning to become pregnant
•Unwilling to use reliable contraception around the timing of the vaccine (one month before and one month after)
•Receiving medication that might reduce immune responses. These include but are not limited to:
- systemic corticosteroids
- interleukins
- interferons
- cyclosporine
- systemic chemotherapy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic (adaptive) random allocation will be achieved using Minimisation. Age will be stratified by 10-year intervals, and sex will be classified as male, female or other, using equal weighting of covariate factors
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
31/08/2026
Actual
Date of last data collection
Anticipated
26/02/2027
Actual
Sample size
Target
88
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 319300 0
Government body
Name [1] 319300 0
NHMRC
Country [1] 319300 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 321792 0
None
Name [1] 321792 0
Address [1] 321792 0
Country [1] 321792 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317878 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 317878 0
Ethics committee country [1] 317878 0
Australia
Date submitted for ethics approval [1] 317878 0
09/05/2025
Approval date [1] 317878 0
30/06/2025
Ethics approval number [1] 317878 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142442 0
Dr Jennifer Juno
Address 142442 0
The Peter Doherty Institute for Infection and Immunity Elizabeth Street Melbourne, VIC 3010
Country 142442 0
Australia
Phone 142442 0
+61 03 8344 9939
Fax 142442 0
Email 142442 0
[email protected]
Contact person for public queries
Name 142443 0
Jennifer Juno
Address 142443 0
The Peter Doherty Institute for Infection and Immunity Elizabeth Street Melbourne, VIC 3010
Country 142443 0
Australia
Phone 142443 0
+61 03 8344 9939
Fax 142443 0
Email 142443 0
[email protected]
Contact person for scientific queries
Name 142444 0
Jennifer Juno
Address 142444 0
The Peter Doherty Institute for Infection and Immunity Elizabeth Street Melbourne, VIC 3010
Country 142444 0
Australia
Phone 142444 0
+61 03 8344 9939
Fax 142444 0
Email 142444 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• De-identified individual participant data:
• Published results
• Primary outcome(s)
• Safety data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
• Teaching research methods or developing new statistical techniques
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
A finite period of: 5 years
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: Dr Jennifer Juno, email [email protected]

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  [email protected]
Ethical approval  [email protected]


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.