Trial Review

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 details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01620801




Registration number
NCT01620801
Ethics application status
Date submitted
12/06/2012
Date registered
15/06/2012
Date last updated
12/03/2019

Titles & IDs
Public title
Hemophilia B Gene Therapy With AAV8 Vector
Scientific title
A Phase 1 Safety Study in Subjects With Severe Hemophilia B (Factor IX Deficiency) Using a Single-Stranded, Adeno-Associated Pseudotype 8 Viral Vector to Deliver the Gene for Human Factor IX
Secondary ID [1] 0 0
AAV8-hFIX19-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia B 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AAV8-hFIX19

Experimental: Low dose - AAV8-hFIX19

Experimental: Middle dose - AAV8-hFIX19

Experimental: High dose - AAV8-hFIX19


Other interventions: AAV8-hFIX19
One-time IV vector administration.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with adverse events related to investigational product
Timepoint [1] 0 0
One year (with 15-year follow-up)
Secondary outcome [1] 0 0
Circulating plasma factor IX levels
Timepoint [1] 0 0
One year (with 15-year follow-up)

Eligibility
Key inclusion criteria
- Willingness to adhere to the clinical protocol and 15-year long-term follow-up as
evidenced by written informed consent

- Adult males at least 18 years of age

- A. Severe FIX deficiency (<1% normal circulating FIX) or B. Moderately severe FIX
deficiency (1-2% normal circulating FIX, inclusive) and a severe bleeding phenotype as
defined by at least one of the following: i. On prophylaxis for a history of bleeding
or ii. On demand therapy with a current or past history of frequent bleeding [4 or
more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain,
joint destruction, and loss of range of motion) in one or more joints]

- No history of inhibitor against FIX

- No history of an allergic reaction or anaphylaxis to FIX products

- Greater than 20 exposure days of treatment with FIX protein

- Anti-AAV8 neutralizing titer measured at < 1:5

- Acceptable laboratory values: hemoglobin = 11% gm; WBC = 3,500/µL; platelets =
100,000/µL; AST, ALT, alkaline phosphatase = 2x ULN; bilirubin = 1.2 gm/dL; and
creatinine = 1.5 gm/dL

- Subject agrees to use barrier contraception until at least two consecutive semen
samples after vector administration are negative for vector sequences (may be for up
to several months)
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with active hepatitis B or C, and HBsAg or HCV RNA viral load positivity,
respectively. Negative viral assays in two samples, collected at least six months
apart, will be required to be considered negative. Both natural clearers and those who
have cleared HCV on antiviral therapy are eligible.

- Subjects currently on antiviral therapy for hepatitis B or C

- Subjects with significant underlying liver disease, as defined by presence of portal
hypertension, splenomegaly, varices, ascites, edema, gastrointestinal bleeding,
encephalopathy, reduction below normal limits of serum albumin, or prior liver biopsy
demonstrating significant fibrosis, specifically = Metavir 3 fibrosis

- Subjects with serological evidence of HIV who have CD4 counts = 200/mm3. Subjects who
are HIV-positive and stable, with an adequate CD4 count (> 200/mm3) and undetectable
viral load (< 50 gc/mL) measured twice in the six months prior to enrollment, on an
antiretroviral drug regimen are eligible to enroll.

- History of inhibitor against FIX

- Anti-AAV8 antibody titers = 1:5

- History of chronic infection or other chronic diseases which the investigators
consider to constitute an unacceptable risk

- Subjects who have participated in a previous gene therapy research trial within one
year of enrollment

- Subjects who have participated in a clinical study with an investigational drug within
six months of enrollment

- Any other condition that would not allow the potential subject to complete follow-up
examinations during the course of the study or, in the opinion of the investigator,
makes the potential subject unsuitable for the study

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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2016
Sample size
Target
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Spark Therapeutics, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Hospital of Philadelphia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Pittsburgh
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Royal Prince Alfred Hospital, Sydney, Australia
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
St. James's Hospital, Ireland
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Hemophilia B is a bleeding disease in males due to very low levels of coagulation factor IX
(FIX) in the blood. The current treatment is intravenous injection of FIX clotting factor
concentrates, in response to bleeding. This study will focus on the severe, most common type
of hemophilia B. This study plans to use a virus called adeno-associated virus (AAV), which
in nature causes no disease, and can be engineered to deliver the human FIX gene (AAV8-hFIX19
vector) to liver cells, where FIX is normally made. This study will use the AAV8-hFIX19
vector.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01620801
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Director
Address 0 0
Spark Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01620801