Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001567314
Ethics application status
Approved
Date submitted
2/11/2017
Date registered
21/11/2017
Date last updated
28/06/2021
Date data sharing statement initially provided
20/02/2019
Date results information initially provided
30/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Validating the optimal dose of normal immunoglobulin for protection against hepatitis A
Scientific title
Validating the optimal dose of normal immunoglobulin for protection against hepatitis A: pharmacokinetics in healthy volunteers
Secondary ID [1] 293266 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hepatitis A 305328 0
Condition category
Condition code
Public Health 304620 304620 0 0
Other public health
Infection 304621 304621 0 0
Other infectious diseases
Oral and Gastrointestinal 304698 304698 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2.5 IU/kg hepatitis A antibodies, which equates to 0.025mL/kg NHIG (Normal Human Immunoglobulin) as a single intramuscular (IM) dose
Intervention code [1] 299526 0
Prevention
Comparator / control treatment
2mL of NHIG as a single dose IM irrespective of weight (200IU hepatitis A antibodies)
Control group
Dose comparison

Outcomes
Primary outcome [1] 303852 0
Quantitative hepatitis A antibody concentration in serum measured according to manufacturer's instructions using Beckmann Coulter Access HAV Ab kit.
Timepoint [1] 303852 0
Days from IM injection of NHIG: 0, 1, 3, 7, 28, 50 (primary timepoint).
Secondary outcome [1] 340277 0
Adverse events: local tenderness, erythema, muscle stiffness, pyrexia, malaise, drowsiness, urticaria, local swelling, headache, nausea, dizziness, any other events volunteered or observed.
Participants will remain under observation for 20 minutes after NHIG administration. Participants will be questioned about any adverse events potentially related to NHIG administration when they return for blood sampling on days 1, 3 and 7.
Timepoint [1] 340277 0
Days after IM injection of NHIG: 0, 1, 3, 7.

Eligibility
Key inclusion criteria
Healthy adult volunteers who provide informed consent, and meet the following criteria will be eligible:
o are immune to measles and rubella according to commercial serology test
o are not immune to hepatitis A according to commercial serology test
o are not eligible for free hepatitis A vaccination and unlikely to require hepatitis A vaccination during the course of study (ie no planned overseas travel)
o weigh at least 51kg
Healthy 17 year olds who provide informed consent, meet the same criteria, and whose parent or guardian also consents will also be eligible.
Minimum age
17 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
o have been in another clinical trial within the last 3 months prior to recruitment to this study
o have history of hypersensitivity, allergy to blood products or haematological disorder
o have received a blood product with the 3 months prior to recruitment to this study
o have been / are to be administered a live virus vaccine within the three weeks prior to NHIG administration
o are pregnant
o have a low platelet count or abnormal results that have not been previously investigated on screening Full blood count.

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)
Group allocation generated by simple randomisation using a random number table to be sealed inside opaque envelopes. Envelopes to be numbered with study ID so that the next numbered envelope will be allocated as a participant is deemed eligible for the trial. Random number table generation and sealing of group allocation inside numbered envelopes to be done by an investigator who will not be involved in assessing eligibility for the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a random number table generated in Excel.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Hepatitis A antibody level for each participant will be plotted against time. GMT and range of hepatitis A antibody concentrations will be recorded for each time point according to study group. The effect of age, sex, study group and antibody level at day 0 on peak antibody levels and levels at day 50 will be modelled. The hepatitis A antibody elimination half-life will be calculated for each group.
Sample size calculation: Sample size was calculated according to a pharmacokinetic modelling study (unpublished at this time) based on published data. To identify a 10% difference in serum hepatitis A antibody titre between the groups at day 50 with 80% power requires a sample size of 19 per arm. The study will attempt to screen 80 potential participants to allow for 50% ineligibility and result in recruitment of 20 participants per study group.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
11/01/2018
Actual
22/05/2018
Date of last participant enrolment
Anticipated
30/08/2019
Actual
15/08/2019
Date of last data collection
Anticipated
4/10/2019
Actual
6/11/2019
Sample size
Target
40
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9334 0
Griffith University Clinical Trials Unit - Southport
Recruitment postcode(s) [1] 18004 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 297896 0
University
Name [1] 297896 0
Griffith University
Country [1] 297896 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
Gold Coast Campus
Southport QLD 4215
Country
Australia
Secondary sponsor category [1] 296951 0
None
Name [1] 296951 0
Address [1] 296951 0
Country [1] 296951 0
Other collaborator category [1] 279792 0
Charities/Societies/Foundations
Name [1] 279792 0
Australian Red Cross Blood Service
Address [1] 279792 0
3/417 St Kilda Rd
Melbourne VIC 3004
Country [1] 279792 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298945 0
Griffith University HREC
Ethics committee address [1] 298945 0
Office for Research
Bray Centre, Nathan Campus
Griffith University
170 Kessels Rd, Nathan QLD 4111
Ethics committee country [1] 298945 0
Australia
Date submitted for ethics approval [1] 298945 0
Approval date [1] 298945 0
08/09/2017
Ethics approval number [1] 298945 0
GU Ref No: 2017/645
Ethics committee name [2] 298947 0
Australian Red Cross Blood Service Human Research Ethics Committee
Ethics committee address [2] 298947 0
17 O'Riordan Street
Alexandria NSW 2015
Ethics committee country [2] 298947 0
Australia
Date submitted for ethics approval [2] 298947 0
Approval date [2] 298947 0
30/10/2017
Ethics approval number [2] 298947 0
2017#29

Summary
Brief summary
Non-immune people exposed to hepatitis A are recommended to receive either hepatitis A vaccine or normal immunoglobulin (which contains hepatitis A antibodies), with the latter recommended for those in the most vulnerable groups. We have previously completed a pharmacokinetic modeling study using published data to estimate the minimum dose of hepatitis A antibodies that would be protective against hepatitis A up to day 50 after injection. This modeling study supported the hypothesis that the current national guideline provides insufficient antibodies for people who weigh over 85kg. The current study seeks to validate these modelling results in order to recommend the optimal dose of normal immunoglobulin for the prevention of hepatitis A. This study will compare the level of antibodies present in blood as a result of passive immunisation with the recommended dose of normal immunoglobulin to the level of antibodies in blood as a result of dosing by weight with the same product in healthy adults. To do this, we will conduct a randomised controlled trial where the usual care group will receive 2mL normal immunoglobulin irrespective of weight, and the test dose group will received 0.025mL/kg to a maximum of 5mL of normal immunoglobulin. Blood samples will be taken from both groups at days 0, 1, 3, 7, 28 and 50 and the groups mean hepatitis A antibody titres compared.
Trial website
https://www.griffith.edu.au/griffith-health/clinical-trial-unit/trials/HepATrial-Registration
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78742 0
Dr Megan Young
Address 78742 0
School of Medicine
Gold Coast Campus
Griffith University
Southport QLD 4215
Country 78742 0
Australia
Phone 78742 0
+61756780624
Fax 78742 0
Email 78742 0
[email protected]
Contact person for public queries
Name 78743 0
Dr Megan Young
Address 78743 0
School of Medicine
Gold Coast Campus
Griffith University
Southport QLD 4215
Country 78743 0
Australia
Phone 78743 0
+61756780624
Fax 78743 0
Email 78743 0
[email protected]
Contact person for scientific queries
Name 78744 0
Dr Megan Young
Address 78744 0
School of Medicine
Gold Coast Campus
Griffith University
Southport QLD 4215
Country 78744 0
Australia
Phone 78744 0
+61756780624
Fax 78744 0
Email 78744 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is not part of the protocol and thus has not been considered by HREC.


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.