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 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
  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: 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:


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 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 16
Study Start Date: September 2012
Estimated Study Completion Date: November 2029
Estimated Primary Completion Date: November 2019 (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)
    • 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, California
Hemophilia Treatment Center at Orthopaedic Hospital Recruiting
Los Angeles, California, United States, 90007
Contact: Doris Quon, MD    213-742-1402    dquon@mednet.ucla.edu   
Contact: Lucy Lacanilao    213-742-1407    LLacanilao@mednet.ucla.edu   
Principal Investigator: Doris Quon, MD, PhD         
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Guy Young, MD    323-361-5507    gyoung@chla.usc.edu   
Contact: Geraldine Pira    323-361-5505    gpira@chla.usc.edu   
Principal Investigator: Guy Young, MD         
University of California Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Maricel Miguelino, MD    916-734-7633    maricel.miguelino@ucdmc.ucdavis.edu   
Contact: Thomas Luu, PhD    916-734-3746    tluu@ucdavis.edu   
Principal Investigator: Jerry S Powell, MD         
University of California at San Diego Medical Center Recruiting
San Diego, California, United States, 92103-8651
Contact: Annette von Drygalski, MD    619-471-0335    avondrygalski@ucsd.edu   
Contact: Thomas J. Cramer, PhD    619-471-0421    tcramer@ucsd.edu   
Principal Investigator: Annette von Drygalski, MD         
United States, Colorado
U of Colorado School of Medicine, Hemophilia & Thrombosis Treatment Center Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Marylin Manco-Johnson, MD    303-724-0365    Marilyn.Manco-Johnson@ucdenver.edu   
Contact: Marylin Manco-Johnson, MD    303-724-0363      
Principal Investigator: Marylin Manco-Johnson, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kesley D Tyson, MS    404-785-9856    kdtyson@emory.edu   
Contact: Beverly Yandell    404-785-4677    byandel@emory.edu   
Principal Investigator: Christine Kempton, MD, MSc         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Rosie Howard    312-942-7902    rosie_howard@rush.edu   
Contact: Erin Craig    312-563-2715    erin_craig@rush.edu   
Principal Investigator: Lisa N Boggio, MD         
United States, Minnesota
University of Minnesota Division of Hematology, Oncology, & Transplantation Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Joni Osip, RN    612-625-1110    JOSIP1@fairview.org   
Contact: Charlotte Quinton, RN,BSN,CCRC    612-626-1421    quint003@umn.edu   
Principal Investigator: Mark Reding, MD         
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Christopher Walsh, MD    212-241-3443    christopher.walsh@mountsinai.org   
Contact: Johanna McCarthy    212-241-8303    johanna.mccarthy@mssm.edu   
Principal Investigator: Christopher E Walsh, MD, PhD         
United States, Oregon
The Hemophilia Center, Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Susan Lattimore, RN    503-418-4495    lattimo@ohsu.edu   
Contact: Kathy Beach, RN    530-494-7425    beachk@ohsu.edu   
Principal Investigator: Michael Recht, MD, PhD         
United States, Texas
Gulf States Hemophilia and Thrombosis Center Recruiting
Houston, Texas, United States, 77030
Contact: Miguel Escobar, MD    713-500-8630    miguel.escobar@uth.tmc.edu   
Contact: Madeline Cantini    713-500-8352    madeline.cantini@uth.tm   
Principal Investigator: Miguel Escobar, MD         
United States, Washington
Puget Sound Blood Center Recruiting
Seattle, Washington, United States, 98104
Contact: Barbara Konkle, MD    206-233-3349    barbarak@psbc.org   
Contact: Steve Grantham, CRC    206-398-5929    SteveG@psbc.org.org   
Principal Investigator: Barbara A Konkle, MD         
Sponsors and Collaborators
Asklepios Biopharmaceutical, Inc.
Investigators
Principal Investigator: Scott WJ McPhee, PhD, MPH Asklepios Biopharmaceutical, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Asklepios Biopharmaceutical, Inc.
ClinicalTrials.gov Identifier: NCT01687608     History of Changes
Other Study ID Numbers: AskBio009-101
Study First Received: August 27, 2012
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

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 April 15, 2014