Hemophilia B
Conditions
Keywords
Hemophilia B, factor IX deficiency, gene therapy
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.
Interventions
BIOLOGICALAskBio009
Single dose IV injection
Sponsors
Baxalta now part of Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients experiencing treatment-related adverse events by dose group | Infusion to Week 3 and Infusion to end of study |
| Change from baseline in clinical laboratory evaluations | Change from baseline at week 3 and change from baseline at the end of study |
Secondary
| Measure | Time frame |
|---|---|
| Changes from Baseline in FIX activity levels, FIX protein levels, and Bleeding Episode Severity & Frequency | At multiple timepoints from pre-dose through up to 5 years post-dose |
| Immune Response to AskBio009 | At multiple timepoints from pre-dose through up to 5 years post-dose |
| Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen | At multiple timepoints from pre-dose through up to 1 years post-dose |
Countries
United States
Contacts
STUDY_DIRECTORStudy Director
Shire
Outcome results
None listed