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

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01687608
• Other study ID #: AskBio009-101
• Secondary ID: 231401
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 11, 2013
• Est. completion date: January 17, 2030

Study information

• Verified date: January 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: January 17, 2030
• Est. primary completion date: January 17, 2030
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• AskBio009
Single dose IV injection

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	U of Colorado School of Medicine, Hemophilia & Thrombosis Treatment Center	Aurora	Colorado
United States	Children's Hospital of Boston	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Gulf States Hemophilia and Thrombosis Center	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Orthopaedic Hemophilia Treatment Center	Los Angeles	California
United States	BloodCenter of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota, Masonic Clinical Research Unit, Clinical and Translational Science Institute	Minneapolis	Minnesota
United States	Mount Sinai Medical Center	New York	New York
United States	The Hemophilia Center, Oregon Health and Science University	Portland	Oregon
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	Bloodworks Northwest	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Baxalta now part of Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients experiencing treatment-related adverse events by dose group		Infusion to Week 3 and Infusion to end of study
Primary	Change from baseline in clinical laboratory evaluations		Change from baseline at week 3 and change from baseline at the end of study
Secondary	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
Secondary	Immune Response to AskBio009		At multiple timepoints from pre-dose through up to 5 years post-dose
Secondary	Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen		At multiple timepoints from pre-dose through up to 1 years post-dose

External Links

•   To obtain more information on the study, click here/on this link