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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.
Verified September 2012 by Asklepios Biopharmaceutical, Inc.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Asklepios Biopharmaceutical, Inc.
ClinicalTrials.gov Identifier:
NCT01687608
First received: August 27, 2012
Last updated: September 20, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Hemophilia B
 Biological: AskBio009
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Factor IX
U.S. FDA Resources

Further study details as provided by Asklepios Biopharmaceutical, Inc.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 16
Study Start Date: September 2012
Estimated Study Completion Date: August 2027
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AskBio009 Dose Escalation
Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
 Biological: AskBio009
Single dose IV injection

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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, per exclusion 9)
    • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687608

Contacts
Contact: Scott WJ McPhee, PhD, MPH 919-968-2727 patient_information@askbio.com

Locations
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Johanna McCarthy     212-241-3935        
Contact     212-241-8303        
Principal Investigator: Christopher E Walsh, MD, PhD            
Sponsors and Collaborators
Asklepios Biopharmaceutical, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Investigators
Principal Investigator: Scott WJ McPhee, PhD, MPH Asklepios Biopharmaceutical, Inc.
  More Information

Additional Information:
Click here for more information about this Phase I/II Hemophilia B Gene Transfer Trial  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Asklepios Biopharmaceutical, Inc.
ClinicalTrials.gov Identifier: NCT01687608     History of Changes
Other Study ID Numbers: AskBio009-101, 1RC3HL103396
Study First Received: August 27, 2012
Last Updated: September 20, 2012
Health Authority: United States: Food and Drug Administration
United States: National Institutes of Health/NHLBI

Keywords provided by Asklepios Biopharmaceutical, Inc.:
Hemophilia B
factor IX deficiency
gene therapy

Additional relevant MeSH terms:
Hemophilia B
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on May 21, 2013