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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 17, 2030

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

  • Biological: AskBio009
    • Single dose IV injection

Arms, Groups and Cohorts

  • Experimental: AskBio009 Dose Escalation
    • Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy

Clinical Trial Outcome Measures

Primary Measures

  • Number of patients experiencing treatment-related adverse events by dose group
    • Time Frame: Infusion to Week 3 and Infusion to end of study
  • Change from baseline in clinical laboratory evaluations
    • Time Frame: Change from baseline at week 3 and change from baseline at the end of study

Secondary Measures

  • Changes from Baseline in FIX activity levels, FIX protein levels, and Bleeding Episode Severity & Frequency
    • Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose
  • Immune Response to AskBio009
    • Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose
  • Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen
    • Time Frame: At multiple timepoints from pre-dose through up to 1 years post-dose

Participating in This Clinical Trial

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 Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Baxalta now part of Shire
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Study Director, Study Director, Shire

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