<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01687608</url>
  </required_header>
  <id_info>
    <org_study_id>AskBio009-101</org_study_id>
    <secondary_id>231401</secondary_id>
    <nct_id>NCT01687608</nct_id>
  </id_info>
  <brief_title>Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baxalta now part of Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor&#xD;
      IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting&#xD;
      Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a&#xD;
      proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX&#xD;
      with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding&#xD;
      episodes. This clinical program will test a gene transfer approach involving the use of a&#xD;
      gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate&#xD;
      the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable&#xD;
      plasma FIX activity between 10% and 40% of normal activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 11, 2013</start_date>
  <completion_date type="Anticipated">October 28, 2030</completion_date>
  <primary_completion_date type="Anticipated">October 28, 2030</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients experiencing treatment-related adverse events by dose group</measure>
    <time_frame>Infusion to Week 3 and Infusion to end of study</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in clinical laboratory evaluations</measure>
    <time_frame>Change from baseline at week 3 and change from baseline at the end of study</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in FIX activity levels, FIX protein levels, and Bleeding Episode Severity &amp; Frequency</measure>
    <time_frame>At multiple timepoints from pre-dose through up to 5 years post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune Response to AskBio009</measure>
    <time_frame>At multiple timepoints from pre-dose through up to 5 years post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen</measure>
    <time_frame>At multiple timepoints from pre-dose through up to 1 years post-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Hemophilia B</condition>
  <arm_group>
    <arm_group_label>AskBio009 Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AskBio009</intervention_name>
    <description>Single dose IV injection</description>
    <arm_group_label>AskBio009 Dose Escalation</arm_group_label>
    <other_name>BAX 335</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males age 18-75 years, inclusive&#xD;
&#xD;
          -  Established hemophilia B with ≥3 hemorrhages per year requiring treatment with&#xD;
             exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding&#xD;
             episodes&#xD;
&#xD;
          -  Plasma FIX activity ≤2% (&lt;1% for first cohort; then per protocol)&#xD;
&#xD;
          -  Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody&#xD;
             negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic&#xD;
             acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative&#xD;
             (undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at&#xD;
             screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Family history of inhibitor to FIX protein or personal laboratory evidence of having&#xD;
             developed inhibitors to FIX protein at any time (&gt;0.6 Bethesda Units on any single&#xD;
             test)&#xD;
&#xD;
          -  Documented prior allergic reaction to any FIX product&#xD;
&#xD;
          -  Detectable AAV8 neutralizing antibodies&#xD;
&#xD;
          -  Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or&#xD;
             more of the following:&#xD;
&#xD;
               -  Platelet count &lt;175,000/μL&#xD;
&#xD;
               -  Albumin ≤3.5 g/dL&#xD;
&#xD;
               -  Total bilirubin &gt;1.5 x ULN and direct bilirubin ≥0.5 mg/dL&#xD;
&#xD;
               -  Alkaline phosphatase &gt;2.0 x ULN&#xD;
&#xD;
               -  ALT or AST &gt;2.0 x ULN (except for subjects who are HIV infected)&#xD;
&#xD;
               -  Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging&#xD;
                  of 2 or greater)&#xD;
&#xD;
               -  History of ascites, varices, variceal hemorrhage or hepatic encephalopathy&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Shire</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Orthopaedic Hemophilia Treatment Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at San Diego Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103-8651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U of Colorado School of Medicine, Hemophilia &amp; Thrombosis Treatment Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>022105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota, Masonic Clinical Research Unit, Clinical and Translational Science Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hemophilia Center, Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gulf States Hemophilia and Thrombosis Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bloodworks Northwest</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BloodCenter of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2012</study_first_posted>
  <last_update_submitted>September 29, 2022</last_update_submitted>
  <last_update_submitted_qc>September 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hemophilia B</keyword>
  <keyword>factor IX deficiency</keyword>
  <keyword>gene therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Hemophilia B</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_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.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01687608
org study id: AskBio009-101
secondary id: 231401
nct id: NCT01687608
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients experiencing treatment-related adverse events by dose group
time frame: Infusion to Week 3 and Infusion to end of study
measure: Change from baseline in clinical laboratory evaluations
time frame: Change from baseline at week 3 and change from baseline at the end of study
measure: 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
measure: Immune Response to AskBio009
time frame: At multiple timepoints from pre-dose through up to 5 years post-dose
measure: 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
arm group label: AskBio009 Dose Escalation
arm group type: Experimental
description: Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
intervention type: Biological
intervention name: AskBio009
description: Single dose IV injection
arm group label: AskBio009 Dose Escalation
other name: BAX 335
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Shire
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hemophilia A
mesh term: Hemophilia B
sharing ipd: Yes
ipd 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.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd 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.
ipd url: https://vivli.org/ourmember/takeda/