Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000214639
Ethics application status
Approved
Date submitted
25/01/2023
Date registered
28/02/2023
Date last updated
28/02/2023
Date data sharing statement initially provided
28/02/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Immunogenicity and safety of the Japanese encephalitis vaccine given intradermally in children and adults
Scientific title
Japanese encephalitis vaccine via intradermal route in children and adults (JEVID-2): A clinical trial comparing the immunogenicity and safety of Japanese encephalitis vaccine administered by subcutaneous and intradermal routes
Secondary ID [1] 308824 0
SCHN: JEVID-2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Japanese encephalitis 328782 0
Condition category
Condition code
Infection 325790 325790 0 0
Other infectious diseases
Inflammatory and Immune System 325791 325791 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of a Japanese encephalitis (JE) vaccine, Imojev, to children aged 5+ years old and adults, either by intradermal or subcutaneous administration under 1:1 randomisation.

The JE vaccine will be administered by trained immunisation nurses in either a hospital/health facility or community venue prepared for the trial.

The JE vaccine contains 4.0-5.8 log plaque forming units of live attenuated recombinant Japanese encephalitis virus per 0.5ml of reconstituted dose.

In the intervention group 450 participants in four age-defined cohorts will receive 0.1mL Imojev by intradermal injection using traditional needle and syringe.

There will be 4 age cohorts as below
5 to <10 years old n=100
10 to <18 years old n=100
18 to <50 years old n=100
> than or equal to 50 years old n=150

The participant will be monitored for any adverse reaction for 30 minutes post vaccination.

Intervention code [1] 325272 0
Prevention
Intervention code [2] 325273 0
Treatment: Drugs
Comparator / control treatment
In the control group 450 participants will receive the JE vaccine, Imojev, by subcutaneous injection (0.5mL)

The JE vaccine contains 4.0-5.8 log plaque forming units of live attenuated recombinant Japanese encephalitis virus per 0.5ml of reconstituted dose.

There will be 4 age cohorts as below
5 to <10 years old n=100
10 to <18 years old n=100
18 to <50 years old n=100
> than or equal to 50 years old n=150
Control group
Active

Outcomes
Primary outcome [1] 333636 0
The proportion of participants achieving seroconversion at 28-35 days following Imojev® vaccine by age and route of administration.

Seroconversion will be defined as:
a. In persons who are seronegative before vaccination the primary parameter for assessment of the immune response will be the proportion reaching plaque reduction neutralisation 50% (PRNT50) titres greater than or equal to 10 after vaccination.
b. In persons who are seropositive at baseline (i.e. have PRNT50 titres greater than or equal to 10) the primary assessment of immune responses to vaccination will be based on proportions achieving substantial increases (e.g. at least a 4-fold rise) in titre after vaccination.

This outcome is assessed by the measurement of serology on serum collected from blood samples during the trial
Timepoint [1] 333636 0
Day 28-35 post vaccination (Visit 3)
Secondary outcome [1] 417832 0
Systemic antibody responses: immunogenicity endpoints will include derived/calculated serum antibody responses specific for JE according to administration route by PRNT50 titres of JE antibodies at:
1. Day 7-10 post vaccination (Visit 2) in a subset only, (the subset will be participants who opt in for this additional blood test)
2. Day 28-35 post vaccination (Visit 3),
3. Day 180-210 post vaccination (Visit 4) and
4. Day 365-395 post vaccination (Visit 5)

This outcome is assessed by the measurement of serology on serum collected from blood samples during the trial
Timepoint [1] 417832 0
1. Day 7-10 post vaccination (Visit 2) in a subset only,
2. Day 28-35 post vaccination (Visit 3),
3. Day 180-210 post vaccination (Visit 4), and
4. Day 365-395 post vaccination (Visit 5)
Secondary outcome [2] 417833 0
The proportion of participants (subset only) achieving seroconversion at 7-10 days following Imojev® vaccine by age and route of administration.

This outcome is assessed by the measurement of serology on serum collected from blood samples during the trial
Timepoint [2] 417833 0
Day 7-10 post-vaccination
Secondary outcome [3] 417834 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Solicited local reactogenicity AEs within 7 days after vaccination by severity score, duration and peak severity;

Local reactogenicity includes, pain, swelling and redness at the injection site and the data is collected from a 7 day self reported paper or electronic diary card
Timepoint [3] 417834 0
Day 7-10 post vaccination (Visit 2),,
Secondary outcome [4] 418683 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Solicited systemic reactogenicity AEs within 7 days after vaccination by severity score, duration and peak severity;

Solicited reactogenicity includes temperature, headache, myalgia, joint pain, vomiting or diarrhoea and the data is collected from a 7 day self reported paper or electronic diary card
Timepoint [4] 418683 0
Day 7-10 day post vaccination (Visit 2)
Secondary outcome [5] 418684 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Unsolicited AEs from Visit 1 (Day 1) to Visit 2 (Day 7-10) after vaccination
- Serious adverse events (SAEs) from Visit 1 (Day 1) to Visit 2 (Day 7-10) after vaccination
- Medically attended adverse events from Visit 1 (Day 1) to Visit 2 (Day 7-10) after vaccination
These data will be analysed together. Presence of AE, SAE or medically attended adverse events will be collected from study participants at the relevant study timepoints. The definition of a serious adverse event and medically attended adverse event is specified in the study protocol and includes hospitalisation or emergency department visit.
Timepoint [5] 418684 0
Day 7-10 post vaccination (Visit 2)
Secondary outcome [6] 418685 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Unsolicited AEs from Visit 2 (Day 7-10) to Visit 3 (Day 28-35) after vaccination
- Serious adverse events (SAEs) from Visit 2 (Day 7-10) to Visit 3 (Day 28-35) after vaccination
- Medically attended adverse events from Visit 2 (Day 7-10) to Visit 3 (Day 28-35) by relatedness after vaccination

these data will be analysed together. Presence of AE, SAE or medically attended adverse events will be collected from study participants at the relevant study timepoints. The definition of a serious adverse event and medically attended adverse event is specified in the study protocol and includes hospitalisation or emergency department visit.
Timepoint [6] 418685 0
Day 28-35 post vaccination (Visit 3)
Secondary outcome [7] 418686 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Unsolicited AEs from Visit 3 (Day 28-35) to Visit 4 (Day 180-210) after vaccination
- Serious adverse events (SAEs) from Visit 3 (Day 28-35) to Visit 4 (Day 180-200) after vaccination
- Medically attended adverse events from Visit 3 (Day 28-35) to Visit 4 (Day 180-210) after vaccination
These data will be analysed together. Presence of AE, SAE or medically attended adverse events will be collected from study participants at the relevant study timepoints. The definition of a serious adverse event and medically attended adverse event is specified in the study protocol and includes hospitalisation or emergency department visit.
Timepoint [7] 418686 0
Day 180-210 after vaccination (Visit 4)
Secondary outcome [8] 418687 0
Safety: The number and percentage of participants reporting adverse events (AEs), will be summarised for the following categories events:
- Unsolicited AEs from Visit 4 (Day 180-210) to Visit 5 (Day 365-395) after vaccination
- Serious adverse events (SAEs) from Visit 4 (Day 180-210) to Visit 5 (Day 365-395) after vaccination
- Medically attended adverse events from Visit 4 (Day 180-210) to Visit 5 (Day 365-395) after vaccination

These data will be analysed together. Presence of AE, SAE or medically attended adverse events will be collected from study participants at the relevant study timepoints. The definition of a serious adverse event and medically attended adverse event is specified in the study protocol and includes hospitalisation or emergency department visit.
Timepoint [8] 418687 0
Day 365-395 post vaccination (Visit 5)

Eligibility
Key inclusion criteria
Potential participants must fulfil all of the following inclusion criteria to be eligible to participate in the study:
- Participants aged 5 years or older at the time of consent.
- For participants aged 5 to less than 18 years: Parents/ guardians willing and capable of providing written informed consent prior to the performance of any study-specific procedure.
OR
For participants aged greater than or equal to 18 years: Willing and capable of providing written informed consent prior to the performance of any study-specific procedure
- The participant must be in good health as determined by the investigator and/or study nurse, as established by pertinent medical history, physical examination and vital signs assessments performed at Screening.
- The participant and parent must be able to attend all scheduled visits and to understand and comply with planned study procedures, in the Investigator’s judgement.
- Participant must not meet jurisdictional health department recommendation for JE vaccine to be given SC
Minimum age
5 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
If any of the following exclusion criteria apply, the potential participant will not be able to participate in the study:
- Participant meets jurisdictional health department recommendation for JE vaccine to be given SC
- Known to previously have had JE disease
- Known to have lived in a JE endemic area outside Australia for greater than6 months
- Previously vaccinated with Imojev® or another JE vaccine
- Participant has a contraindication to JE vaccines
o anaphylaxis after a previous dose of any JE vaccine
o anaphylaxis after any component of a JE vaccine
- Previously vaccinated with dengue or yellow fever vaccines, or planning to have these vaccines during the first two months after receipt of the JE vaccine
- A history of dengue fever
- Pregnant women or planning pregnancy
- Breastfeeding or planning to breastfeed
- Participant receiving immunosuppressive medication or has medical condition(s) that impaired the normal functioning of the immune system (definitions as per the Australian Immunisation Handbook)
- History of any major (per Investigator’s discretion) cardiovascular, renal, neurological, metabolic, gastrointestinal, hepato-biliary, uncontrolled hypertension and diabetes, clinically significant chronic pulmonary disease, immunological and autoimmune diseases or any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
- Chronic use (more than 14 continuous days) of any dose of systemic corticosteroids within 30 days prior to Screening. Intra-articular, intra-bursal, or topical (skin or eyes) corticosteroids are permitted.
- Have (or have a family member who has) had a severe reaction to a live attenuated viral vaccine, or are related to someone with known IFNAR1 deficiency
- Have had a severe reaction to the MMR vaccine
- History of known or suspected hypersensitivity or any severe allergic reaction including anaphylaxis, generalised urticaria, angioedema, and other significant reaction to Imojev® vaccine or any vaccine component).
- Presence of active viral or bacterial infection, with or without fever (oral temperature greater than or equal to 37.8C) at Screening or within 72 hours prior to vaccination, if determined by the Investigator to be of clinical significance (enrolment may be delayed for full recovery if acceptable to the Investigator).
- Participating in any other clinical study and have received any other investigational product (i.e. study vaccine, drug, biologic or device) within 30 days or 5 half-lives (whichever is longer) prior to Screening, or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with the interpretation of the assessments in this study.
- Received or plans to receive a live-attenuated vaccine within 4 weeks before or after each study vaccination
- Received immunoglobulins and/or any blood or blood products within 3 months before vaccination or plans to receive any blood or blood products at any time during the study.
- Has any psychiatric or cognitive disease that, in the opinion of the Investigator, may interfere with the participant's ability to participate in the study.

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)
The clinician determining if a participant is eligible for inclusion in the trial is unaware, when this decision was made, to which group the subject would be allocated. Allocation will be concealed by central randomisation done at the NHMRC Clinical trials centre.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants who meet the eligibility criteria and consent to the study will be randomised to receive Imojev® administered subcutaneously or intradermally.

Randomisation will occur within the cohorts (that are age stratified) and performed by the NHMRC Clinical Trial Centre. Simple randomisation will occur using computer software (i.e. computerised sequence generation) at the NHMRC Clinical trials centre
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be used to report the baseline characteristics of the participants. The outcomes of interest (i.e., seroconversion rates [PRNT50 titre greater than or equal to 10] at day 7-10, day 28-35, after ID vaccination and subcutaneous vaccination, and rate of Adverse Events Following Immunisation (AEFIs)) will be estimated using the number of participants with the outcomes over the total number of participants, and compared between routes of administration. The geometric mean titre (GMT) against JE genotypes III and IV will be estimated by log transforming the observed titres for each participant and calculating the arithmetic mean.
The severity of AEFI will be determined using the severity grade described in the study protocol.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/01/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
900
Accrual to date
77
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 39341 0
2594 - Young

Funding & Sponsors
Funding source category [1] 313049 0
Government body
Name [1] 313049 0
NSW Ministry of Health
Country [1] 313049 0
Australia
Primary sponsor type
Hospital
Name
Sydney Children's Hospital Network
Address
Cnr Hainsworth St and Hawkesbury rds
Westmead
NSW 2145
Country
Australia
Secondary sponsor category [1] 314736 0
None
Name [1] 314736 0
Address [1] 314736 0
Country [1] 314736 0
Other collaborator category [1] 282528 0
Other Collaborative groups
Name [1] 282528 0
Queensland Institute of Medical Research
Address [1] 282528 0
300 Herston Rd, Herston QLD 4006, Australia
Country [1] 282528 0
Australia
Other collaborator category [2] 282530 0
Individual
Name [2] 282530 0
Professor Colleen Lau
Address [2] 282530 0
University of Queensland
St Lucia
Queensland 4072
Country [2] 282530 0
Australia
Other collaborator category [3] 282531 0
Individual
Name [3] 282531 0
Dr Luis Furuya
Address [3] 282531 0
University of Queensland
St Lucia
Queensland 4072
Country [3] 282531 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312301 0
Sydney Children's Hospital Network Human Research Ethics Committee
Ethics committee address [1] 312301 0
Cnr Hainsworth St and Hawkesbury Rd
Westmead
NSW 2145
Ethics committee country [1] 312301 0
Australia
Date submitted for ethics approval [1] 312301 0
Approval date [1] 312301 0
08/01/2023
Ethics approval number [1] 312301 0
2022/ETH02471

Summary
Brief summary
Australia is on the cusp of a potential outbreak of Japanese encephalitis (JE) viral infections as we move into spring and summer and having back-to-back La Niña seasons. There are effective JE vaccines which are licensed for children over 9 months old and given by subcutaneous (SC) injection. Intradermal (ID) vaccine administration only uses 1/5 of the subcutaneous dose and is therefore “dose sparing” enabling more people to be vaccinated from each vaccine vial. ID JE vaccination has found to be safe and immunogenic in adults, however has not yet been tested in children and adolescents.

One recent study suggests that as much as 3% of the Australian population may be at risk of JE virus (JEV) exposure. In a naïve population, the risk of severe disease is likely to be equally distributed between age-groups. Of the 6 JEV deaths recorded in 2022, one was an infant.

The aim of this project is to study immunogenicity and safety of JE viral vaccine (Imojev®) given ID using traditional needle and syringe in children and adults and to compare safety and immunogenicity with Imojev® given via the current recommended SC route.

The results will be useful to inform vaccination programs if there is a significant JEV outbreak and especially if we have insufficient supplies of JE vaccines in Australia to vaccinate our most at risk populations, including children.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124166 0
Prof Nicholas Wood
Address 124166 0
The Children's Hospital at Westmead
Cnr Hainsworth St and Hawkesbury Rd
Westmead NSW 2145
Country 124166 0
Australia
Phone 124166 0
+61 2 9845 1429
Fax 124166 0
Email 124166 0
nicholas.wood@health.nsw.gov.au
Contact person for public queries
Name 124167 0
Prof Nicholas Wood
Address 124167 0
The Children's Hospital at Westmead
Cnr Hainsworth St and Hawkesbury Rd
Westmead NSW 2145
Country 124167 0
Australia
Phone 124167 0
+61 2 9845 1429
Fax 124167 0
Email 124167 0
nicholas.wood@health.nsw.gov.au
Contact person for scientific queries
Name 124168 0
Prof Nicholas Wood
Address 124168 0
The Children's Hospital at Westmead
Cnr Hainsworth St and Hawkesbury Rd
Westmead NSW 2145
Country 124168 0
Australia
Phone 124168 0
+61 2 9845 1429
Fax 124168 0
Email 124168 0
nicholas.wood@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No ethics approval to do so.


What supporting documents are/will be available?

No Supporting Document Provided



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.