Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
- Registration Number
- NCT01687608
- Lead Sponsor
- Baxalta now part of Shire
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 30
- 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
-
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
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AskBio009 Dose Escalation AskBio009 Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen At multiple timepoints from pre-dose through up to 1 years post-dose 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
Trial Locations
- Locations (15)
Orthopaedic Hemophilia Treatment Center
🇺🇸Los Angeles, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Children's Hospital of Boston
🇺🇸Boston, Massachusetts, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of California at San Diego Medical Center
🇺🇸San Diego, California, United States
U of Colorado School of Medicine, Hemophilia & Thrombosis Treatment Center
🇺🇸Aurora, Colorado, United States
University of Minnesota, Masonic Clinical Research Unit, Clinical and Translational Science Institute
🇺🇸Minneapolis, Minnesota, United States
The Hemophilia Center, Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Gulf States Hemophilia and Thrombosis Center
🇺🇸Houston, Texas, United States
Bloodworks Northwest
🇺🇸Seattle, Washington, United States
BloodCenter of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States