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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01687608
Recruitment Status : Active, not recruiting
First Posted : September 19, 2012
Last Update Posted : September 30, 2022
Information provided by (Responsible Party):
Takeda ( Baxalta now part of Shire )

Brief 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.

Condition or disease Intervention/treatment Phase
Hemophilia B Biological: AskBio009 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : February 11, 2013
Estimated Primary Completion Date : October 28, 2030
Estimated Study Completion Date : October 28, 2030

Arm Intervention/treatment
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
Other Name: BAX 335

Primary Outcome Measures :
  1. Number of patients experiencing treatment-related adverse events by dose group [ Time Frame: Infusion to Week 3 and Infusion to end of study ]
  2. 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 Outcome Measures :
  1. 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 ]
  2. Immune Response to AskBio009 [ Time Frame: At multiple timepoints from pre-dose through up to 5 years post-dose ]
  3. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01687608

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United States, California
Orthopaedic Hemophilia Treatment Center
Los Angeles, California, United States, 90007
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California Davis Medical Center
Sacramento, California, United States, 95817
University of California at San Diego Medical Center
San Diego, California, United States, 92103-8651
United States, Colorado
U of Colorado School of Medicine, Hemophilia & Thrombosis Treatment Center
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 022105
United States, Minnesota
University of Minnesota, Masonic Clinical Research Unit, Clinical and Translational Science Institute
Minneapolis, Minnesota, United States, 55455
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Oregon
The Hemophilia Center, Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Gulf States Hemophilia and Thrombosis Center
Houston, Texas, United States, 77030
United States, Washington
Bloodworks Northwest
Seattle, Washington, United States, 98104
United States, Wisconsin
BloodCenter of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Baxalta now part of Shire
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Study Director: Study Director Shire
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT01687608    
Other Study ID Numbers: AskBio009-101
231401 ( Other Identifier: Sponsor )
First Posted: September 19, 2012    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Baxalta now part of Shire ):
Hemophilia B
factor IX deficiency
gene therapy
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked