Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: AskBio009


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AskBio009 Dose Escalation<br>Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy | Biological: AskBio009<br>* Single dose IV injection<br>* Other names: BAX 335;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia B, factor IX deficiency, gene therapy