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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Asklepios Biopharmaceutical, Inc.
Sponsor:
Information provided by (Responsible Party):
Asklepios Biopharmaceutical, Inc.
ClinicalTrials.gov Identifier:
NCT01687608
First received: August 27, 2012
Last updated: March 25, 2014
Last verified: March 2014

August 27, 2012
March 25, 2014
September 2012
November 2019   (final data collection date for primary outcome measure)
  • Number of patients experiencing treatment-related adverse events by dose group [ Time Frame: Infusion to Week 3 and Infusion to end of study ] [ Designated as safety issue: Yes ]
  • Change from baseline in clinical laboratory evaluations [ Time Frame: Change from baseline at week 3 and change from baseline at the end of study ] [ Designated as safety issue: Yes ]
  • Number of patients experiencing treatment-related adverse events by dose group [ Time Frame: Infusion - Week 3 and Infusion - end of study ] [ Designated as safety issue: Yes ]
  • Change from baseline in clinical laboratory evaluations [ Time Frame: Change from baseline at week 3 and change from baseline at the end of study ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01687608 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Immune Response to AskBio009 [ Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Changes from Baseline in FIX levels and Bleeding Episode Severity & Frequency [ Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose ] [ Designated as safety issue: Yes ]
  • Immune Response to AskBio009 [ Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
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

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Hemophilia B
Biological: AskBio009
Single dose IV injection
Experimental: AskBio009 Dose Escalation
Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
Intervention: Biological: AskBio009
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
16
November 2029
November 2019   (final data collection date for primary outcome measure)

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
Male
18 Years to 75 Years
No
Contact: Scott WJ McPhee, PhD, MPH 919-968-2727 patient_information@askbio.com
United States
 
NCT01687608
AskBio009-101
Yes
Asklepios Biopharmaceutical, Inc.
Asklepios Biopharmaceutical, Inc.
Not Provided
Principal Investigator: Scott WJ McPhee, PhD, MPH Asklepios Biopharmaceutical, Inc.
Asklepios Biopharmaceutical, Inc.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP