Brief Title
Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
Official Title
A Phase 1/2 Open-Label, Single Ascending Dose Trial of a Self-Complementing Optimized Adeno-associated Virus Serotype 8 Factor IX Gene Therapy (AskBio009) in Adults With Hemophilia B
Brief Summary
The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor
IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.
Detailed Description
Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting
Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a
proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX
with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding
episodes. This clinical program will test a gene transfer approach involving the use of a
gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate
the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable
plasma FIX activity between 10% and 40% of normal activity.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Number of patients experiencing treatment-related adverse events by dose group
Secondary Outcome
Changes from Baseline in FIX activity levels, FIX protein levels, and Bleeding Episode Severity & Frequency
Condition
Hemophilia B
Intervention
AskBio009
Study Arms / Comparison Groups
AskBio009 Dose Escalation
Description: Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
30
Start Date
February 11, 2013
Completion Date
July 31, 2022
Primary Completion Date
July 31, 2022
Eligibility Criteria
Inclusion Criteria:
- Males age 18-75 years, inclusive
- Established hemophilia B with ≥3 hemorrhages per year requiring treatment with
exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding
episodes
- Plasma FIX activity ≤2% (<1% for first cohort; then per protocol)
- Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody
negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic
acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative
(undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at
screening
Exclusion Criteria:
- Family history of inhibitor to FIX protein or personal laboratory evidence of having
developed inhibitors to FIX protein at any time (>0.6 Bethesda Units on any single
test)
- Documented prior allergic reaction to any FIX product
- Detectable AAV8 neutralizing antibodies
- Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or
more of the following:
- Platelet count <175,000/μL
- Albumin ≤3.5 g/dL
- Total bilirubin >1.5 x ULN and direct bilirubin ≥0.5 mg/dL
- Alkaline phosphatase >2.0 x ULN
- ALT or AST >2.0 x ULN (except for subjects who are HIV infected)
- Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging
of 2 or greater)
- History of ascites, varices, variceal hemorrhage or hepatic encephalopathy
Gender
Male
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Study Director, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01687608
Organization ID
AskBio009-101
Secondary IDs
231401
Responsible Party
Sponsor
Study Sponsor
Baxalta now part of Shire
Study Sponsor
Study Director, Study Director, Shire
Verification Date
February 2022