Current Environment:

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.

Conditions

Hemophilia B

Recruitment Status

ACTIVE_NOT_RECRUITING

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.

Eligibility Criteria

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

Intervention

Intervention Type

Intervention Name

BIOLOGICAL

AskBio009

Phase

PHASE1, PHASE2

Gender

MALE

Min Age

18 Years

Max Age

75 Years

Download Date

2024-01-31

Principal Investigator

N/A

Primary Contact Information

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team:

Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B NCT01687608