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Trial registered on ANZCTR


Registration number
ACTRN12621001059853
Ethics application status
Approved
Date submitted
29/06/2021
Date registered
11/08/2021
Date last updated
11/08/2021
Date data sharing statement initially provided
11/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating typhoid vaccine responses in specific antibody deficiency patients receiving immunoglobulin replacement.
Scientific title
Evaluating Vi-polysaccharide vaccine responses in specific antibody deficiency patients receiving immunoglobulin replacement.
Secondary ID [1] 304647 0
Nil known
Universal Trial Number (UTN)
U1111-1267-3201
Trial acronym
VISAD Study
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Specific antibody deficiency
322592 0
Common variable immunodeficiency 322593 0
Condition category
Condition code
Inflammatory and Immune System 320208 320208 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose of Vi-polysaccharide vaccine (0.5ml intramuscular injection)
Intervention code [1] 320995 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328079 0
Immunological laboratory assays to assess humoral responses (anti-Vi IgG titres) to Vi-PS vaccination at baseline and post-vaccination time points using blood samples from patients with SAD.
Timepoint [1] 328079 0
Anti-Vi IgG titres will be assessed at baseline and 28 days after vaccination.
Primary outcome [2] 328578 0
Immunological laboratory assays to assess cellular responses (Vi-specific antibody secreting cells) to Vi-PS vaccination at baseline and post-vaccination time points using blood samples from patients with SAD.
Timepoint [2] 328578 0
Frequencies of Vi-specific antibody secreting cells will be assessed at baseline and day 7 post-vaccination
Secondary outcome [1] 397518 0
Description of the proportion of Group 1 patients who have successfully remained off immunoglobulin replacement at completion of the study versus those who have had immunoglobulin replacement recommenced. Participants will be asked at study visits if they have recommenced immunoglobulin replacement .
Timepoint [1] 397518 0
13 months post-vaccination
Secondary outcome [2] 397519 0
Immunological laboratory assays to assess humoral and cell-mediated responses to Vi-PS vaccination at baseline and post-vaccination time points, using blood samples, to compare responses between patients with SAD, CVID and healthy controls. This is a composite outcome assessing both anti-Vi IgG titres and frequencies of Vi-specific antibody secreting cells
Timepoint [2] 397519 0
Anti-Vi IgG titres will be assessed at baseline and 28 days after vaccination.
B cell responses will be assessed at baseline and 7 days after vaccination.
Secondary outcome [3] 397521 0
Immunological laboratory assays to assess humoral and cell-mediated responses to Vi-PS vaccination at baseline and post-vaccination time points, using blood samples, to compare responses in Group 1 (SAD patients who have immunoglobulin replacement stopped) and Group 2 (SAD patients who remain on immunoglobulin replacement) patients. This is a composite outcome assessing both anti-Vi IgG titres and frequencies of Vi-specific antibody secreting cells.
Timepoint [3] 397521 0
Anti-Vi IgG titres will be assessed at baseline, 1, 6 and 13 months after vaccination.
B cell responses will be assessed at baseline and 7 days after vaccination.
Secondary outcome [4] 397522 0
Clinical outcomes (evaluated at the final study visit through participant questioning) will be compared between Group 1 and Group 2 participants, and will include a composite of the following:
a. Number of infections requiring antibiotic treatment over the duration of the study
b. Number of infections resulting in hospitalisation or requiring intravenous antibiotic treatment
c. Number of patients commenced on long-term prophylactic antibiotics
d. Total number of days of antibiotic treatment over the study period
Timepoint [4] 397522 0
13 months after vaccination
Secondary outcome [5] 397523 0
Description of the number of participants enrolled in the study at the 13- month post-vaccination times point (i.e. Visit 5) for each study group. This will be performed by reviewing participant retention and withdrawals over the duration of the study by auditing study records.
Timepoint [5] 397523 0
13 months after vaccination

Eligibility
Key inclusion criteria
Four groups of participants will be included in this study.
1. Group 1= Adult SAD patients on immunoglobulin replacement awaiting a trial cessation period off immunoglobulin replacement
2. Group 2 = Adult SAD patients on long-term immunoglobulin replacement, due to previously failing a trial off immunoglobulin replacement, or deemed medically not suitable for a trial
3. Group 3 = Adult CVID patients on immunoglobulin replacement
4. Group 4 = Adult healthy controls

General inclusion criteria applicable across the groups includes:
• Consenting adult volunteers 18 years and above.
• Individuals willing to have blood samples collected and attend all study visits.

For Groups 1-3
• Diagnosis of SAD (for Groups 1 and 2) or CVID (Group 3), according to Australian National Blood Authority guidelines, and receiving immunoglobulin replacement (with any product type) for greater than 6 months, at the time of enrolment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
General exclusion criteria include:
• Age <18 years.
• Individuals unable to provide informed consent.
• Individuals unable to attend study visits.
• Previous allergic reaction to Vi-polysaccharide vaccine or vaccine components.
• Received B cell depletion treatment within the last 2 years (e.g. Rituximab, Ocrelizumab etc.).
• Pregnant or breast-feeding at the time of study enrolment.

Additional exclusion criteria for healthy controls:
- Vi-polysaccharide vaccination within the last 2 years
- Immunosuppressive state including current treatment with immunosuppressive agents, active haematological malignancy, treatment with chemotherapy or radiotherapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis
Descriptive statistics will be presented on the clinical and biological data for the cohort as a whole. As well, descriptive statistics will be presented to answer the objectives listed above (i.e. primary objective and secondary objectives i, iii and iv). Normally distributed data will be presented as means and standard deviations, skewed data presented as medians and interquartile ranges, counts as number (%).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 19830 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 19831 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 19832 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 34519 0
3050 - Parkville
Recruitment postcode(s) [2] 34520 0
3168 - Clayton
Recruitment postcode(s) [3] 34521 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 309009 0
Charities/Societies/Foundations
Name [1] 309009 0
Allergy and Immunology Foundation of Australasia
Address [1] 309009 0
PO Box 450, Balgowlah NSW 2093, Australia
Country [1] 309009 0
Australia
Funding source category [2] 309019 0
Government body
Name [2] 309019 0
National Blood Sector Research and Development Program
Address [2] 309019 0
National Blood Authority
Locked Bag 8430
Canberra ACT 2601
Australia
Country [2] 309019 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Royal Melbourne Hospital
300 Grattan Street, Victoria 3050
Country
Australia
Secondary sponsor category [1] 309953 0
None
Name [1] 309953 0
Address [1] 309953 0
Country [1] 309953 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308896 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 308896 0
Office for Research
The Royal Melbourne Hospital
Level 2 South West
300 Grattan Street
Parkville, Victoria 3050
Ethics committee country [1] 308896 0
Australia
Date submitted for ethics approval [1] 308896 0
23/02/2021
Approval date [1] 308896 0
16/06/2021
Ethics approval number [1] 308896 0
HREC/73845/MH-2021

Summary
Brief summary
Patients with specific antibody deficiency (SAD) have impaired immune function and suffer from recurrent infections. Some patients are treated with immunoglobulin replacement which involves receiving monthly infusions of pooled protective antibodies from healthy blood donors.

This multi-centre study will be the first to investigate vaccine responses to a commonly used typhoid vaccine (Vi-polysaccharide; Vi-PS) in adult patients with SAD on immunoglobulin replacement. We hypothesise that Vi-PS vaccine responses will differ between SAD patients, in particular those who require long-term immunoglobulin replacement and those with less severe disease.

This study will describe Vi-PS vaccine responses in SAD patients both on and off immunoglobulin replacement as well as healthy adults and patients with known antibody deficiency (common variable immunodeficiency). These groups will help us to understand normal and abnormal Vi-PS vaccine responses. Having more information on how to assess SAD patients on immunoglobulin replacement will help clinicians to better manage patients with SAD in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112258 0
Dr Celina Jin
Address 112258 0
Royal Melbourne Hospital
300 Grattan Street
Parkville, Victoria 3050
Country 112258 0
Australia
Phone 112258 0
+61 3 93427191
Fax 112258 0
Email 112258 0
celina.jin@mh.org.au
Contact person for public queries
Name 112259 0
Dr Celina Jin
Address 112259 0
Royal Melbourne Hospital
300 Grattan Street
Parkville, Victoria 3050
Country 112259 0
Australia
Phone 112259 0
+61 3 93427191
Fax 112259 0
Email 112259 0
celina.jin@mh.org.au
Contact person for scientific queries
Name 112260 0
Dr Celina Jin
Address 112260 0
Royal Melbourne Hospital
300 Grattan Street
Parkville, Victoria 3050
Country 112260 0
Australia
Phone 112260 0
+61 3 93427191
Fax 112260 0
Email 112260 0
celina.jin@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Risk of breaching confidentiality given small sample size and uncommon disease conditions.
What supporting documents are/will be available?
No other documents available
Summary results
No Results