ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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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

ACTRN12617001099314

Ethics application status

Approved

Date submitted

25/07/2017

Date registered

28/07/2017

Date last updated

10/11/2021

Date data sharing statement initially provided

13/05/2019

Date results provided

10/11/2021

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]

None

Universal Trial Number (UTN)

U1111-1199-8092

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Haemophilia A

Haemophilia B

Condition category

Condition code

Blood

Clotting disorders

Human Genetics and Inherited Disorders

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]

Not applicable

Comparator / control treatment

No control group.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

Single visit.

Primary outcome [2]

Immune status against AAV, assessed as a titre for serum AAV-neutralising antibody.

Timepoint [2]

Single visit.

Secondary outcome [1]

None.

Timepoint [1]

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

Sex

Males

Can healthy volunteers participate?

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

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

Laboratory conducting the sample testing halted all testing.

Date of first participant enrolment

Anticipated

Actual

19/08/2009

Date of last participant enrolment

Anticipated

Actual

4/09/2019

Date of last data collection

Anticipated

Actual

6/07/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

Royal Prince Alfred Hospital - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Department of Cell & Molecular Therapies, Royal Prince Alfred Hospital

Address [1]

Level 2, Building 89
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050

Country [1]

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]

Commercial sector/Industry

Name [1]

Spark Therapeutics, Inc.

Address [1]

Spark Therapeutics, Inc.
3737 Market Street
Philadelphia, PA 19104

Country [1]

United States of America

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District (RPA Zone) Ethics Review Committee

Ethics committee address [1]

Research Ethics and Governance Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/03/2009

Approval date [1]

07/04/2009

Ethics approval number [1]

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

Prof John Rasko

Address

Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 4860

Fax

+61 2 9515 4868

slhd-rpacmttrials@sswahs.nsw.gov.au

Contact person for public queries

Name

Divya Suthar

Address

Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 4865

Fax

+61 2 9515 4868

slhd-rpacmttrials@health.nsw.gov.au

Contact person for scientific queries

Name

Aimei Lee

Address

Department of Cell & Molecular Therapies
Royal Prince Alfred Hospital
Level 2, Building 89
Missenden Road
CAMPERDOWN NSW 2050

Country

Australia

Phone

+61 2 9515 4860

Fax

+61 2 9515 4868

slhd-rpacmttrials@health.nsw.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
8614	Study protocol			slhd-rpacmttrials@health.nsw.gov.au

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.

Trial Review

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