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Trial registered on ANZCTR


Registration number
ACTRN12617001099314
Ethics application status
Approved
Date submitted
25/07/2017
Date registered
28/07/2017
Date last updated
27/07/2020
Date data sharing statement initially provided
13/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Genotype and Adeno-Associated Virus (AAV) Immune Status of Patients with Inherited Blood Diseases (Haemophilia A and B)
Scientific title
Genotype and Adeno-Associated Virus (AAV) Immune Status of Patients with Inherited Blood Diseases (Haemophilia A and B)
Secondary ID [1] 292524 0
None
Universal Trial Number (UTN)
U1111-1199-8092
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haemophilia A 304170 0
Haemophilia B 304171 0
Condition category
Condition code
Blood 303497 303497 0 0
Clotting disorders
Human Genetics and Inherited Disorders 303530 303530 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is an observational, data collecting, non-interventional study. Patients who agree to participate will have a single blood sample taken on a single occasion. The sample will be used to determine the participant's immune status against Adeno-Associated Virus (AAV), a potential vector for therapeutic, curative gene therapy. If the participant has not previously had their haemophilia genotype determined, this test will also be offered, and if accepted, performed upon the same blood sample.
Intervention code [1] 298709 0
Not applicable
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302873 0
Genotype analysis for Haemophilia A/B, assesed by a DNA sequence analysis at a reference laboratory to determine the particular disease-causing mutation.
Timepoint [1] 302873 0
Single visit.
Primary outcome [2] 302900 0
Immune status against AAV, assessed as a titre for serum AAV-neutralising antibody.
Timepoint [2] 302900 0
Single visit.
Secondary outcome [1] 337283 0
None.
Timepoint [1] 337283 0
None.

Eligibility
Key inclusion criteria
1. Male of 18 years or older.
2. Hereditary blood disease, including Haemophilia A or B.
3. Able to provide informed consent according to the guidelines of the Sydney Local Health District Ethics Review Committee.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with a blood disease not due to a genetic mutation.
2. Subjects with less than 1-year life expectancy.
3. Investigator judgment that subject will be unable to comply with study endpoints.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
Biostatistical analyses will be focused on the frequency of mutations (nonsense mutations, for example) and the frequency of AAV immunity in the subjects, along with the confidence limits attached to those frequencies.

Recruitment
Recruitment status
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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 8611 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 16719 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 297092 0
Hospital
Name [1] 297092 0
Department of Cell & Molecular Therapies, Royal Prince Alfred Hospital
Address [1] 297092 0
Level 2, Building 89
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Country [1] 297092 0
Australia
Primary sponsor type
Hospital
Name
Department of Cell & Molecular Therapies, Royal Prince Alfred Hospital
Address
Level 2, Building 89
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 296102 0
Commercial sector/Industry
Name [1] 296102 0
Spark Therapeutics, Inc.
Address [1] 296102 0
Spark Therapeutics, Inc.
3737 Market Street
Philadelphia, PA 19104
Country [1] 296102 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298270 0
Sydney Local Health District (RPA Zone) Ethics Review Committee
Ethics committee address [1] 298270 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 298270 0
Australia
Date submitted for ethics approval [1] 298270 0
17/03/2009
Approval date [1] 298270 0
07/04/2009
Ethics approval number [1] 298270 0
X09-0049

Summary
Brief summary
The current method of treating patients with bleeding disorders such as haemophilia A and haemophilia B is by injection of recombinant factor VIII or IX, respectively. Even though there is evidence that prophylactic (continuous) injection of factor prevents long-term complications of the disease, cost is prohibitive. The cost for “on-demand” treatment is approximately $100,000, or more, per year for many adults. Some patients form “inhibitors” (neutralizing antibodies against coagulation factor) which increases the amount of factor needed for treatment, and the associated expense. In view of the cost, inconvenience of injections and the potential for inhibitor formation, effective alternative therapies would be welcome by hemophilic patients.

One research approach for haematological diseases involves gene transfer. A research effort towards clinical gene transfer for haemophilia, including Professor John Rasko at RPAH, has focused on viral vector delivery systems based on the adeno-associated virus (AAV). Clinical trials over the past decade have demonstrated the utility of AAV vectors for the delivery of normal factor transgenes to muscle and liver. However, immune responses against AAV capsid (the viral vector “coat”) have prematurely terminated factor expression, most likely by immunologically “clearing” vector-transduced hepatocytes. Initial data indicates that approximately 50% of the haemophilia patient population has pre-existing immunity to AAV, as measured by serum antibodies. Clinical studies incorporating immune modulation have been approved, but there is a need to know the AAV immune status of a number of patients, prior to proposing the research study to patients.

Therefore, this study intends to screen a number of patients with haemophilia A and B in order to determine their immune system response to AAV, and the genotype of their disease-causing mutation. Depending on the results of these tests, participants may be offered the opportunity to participate in interventional gene therapy trials for their particular disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76542 0
Prof John Rasko
Address 76542 0
Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050
Country 76542 0
Australia
Phone 76542 0
+61 2 9515 4860
Fax 76542 0
+61 2 9515 4868
Email 76542 0
slhd-rpacmttrials@sswahs.nsw.gov.au
Contact person for public queries
Name 76543 0
Ms Divya Suthar
Address 76543 0
Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050
Country 76543 0
Australia
Phone 76543 0
+61 2 9515 4865
Fax 76543 0
+61 2 9515 4868
Email 76543 0
slhd-rpacmttrials@health.nsw.gov.au
Contact person for scientific queries
Name 76544 0
Dr Aimei Lee
Address 76544 0
Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050
Country 76544 0
Australia
Phone 76544 0
+61 2 9515 4860
Fax 76544 0
+61 2 9515 4868
Email 76544 0
slhd-rpacmttrials@sswahs.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
Due to the very small number of patients with these rare diseases, and the collection of genotype data, it will not be possible to adequately deidentify individual participant data for distribution.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 8614 0
Study protocol
Citation [1] 8614 0
Link [1] 8614 0
Email [1] 8614 0
slhd-rpacmttrials@health.nsw.gov.au
Other [1] 8614 0
Attachment [1] 8614 0
Summary results
No Results