<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/NCT03239392</url>
  </required_header>
  <id_info>
    <org_study_id>BNZ1-CT-201</org_study_id>
    <nct_id>NCT03239392</nct_id>
  </id_info>
  <brief_title>A Dose-Ranging Study of IV BNZ-1 in LGL Leukemia or Refractory CTCL</brief_title>
  <official_title>A Dose-Ranging Study of Intravenous BNZ132-1-40 in Patients With Large Granular Lymphocyte Leukemia or Refractory Cutaneous T-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioniz Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bioniz Therapeutics</source>
  <oversight_info>
    <has_dmc>No</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>
      This study is an open-label, multi-center, dose-ranging study to characterize the safety,&#xD;
      tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered&#xD;
      weekly by IV infusion to adults diagnosed with Large Granular Lymphocyte (LGL) Leukemia or&#xD;
      refractory Cutaneous T-cell Lymphoma (CTCL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open-label, multi-center, dose-ranging study to characterize the safety,&#xD;
      tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered&#xD;
      weekly by IV infusion to adults diagnosed with LGL or CTCL. The study has 5 periods:&#xD;
&#xD;
        -  Screening Period&#xD;
&#xD;
        -  4-week Treatment Period&#xD;
&#xD;
        -  3-month Treatment Extension Period&#xD;
&#xD;
        -  Long-term Extension Period (open-ended)&#xD;
&#xD;
        -  6-week Follow-up Period Subjects will be screened for eligibility within 30 days of&#xD;
           study Day 1 (first dosing day of the 4-Week Treatment Period).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2018</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</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>Incidence, severity and relationship of treatment-emergent adverse events</measure>
    <time_frame>1 month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence, severity and relationship of treatment-emergent adverse events</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics</measure>
    <time_frame>16 weeks</time_frame>
    <description>Flow cytometry: Change from baseline over time for Tregs, NK cells and CD8+ central memory T-cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-dose and steady-state Cmax</measure>
    <time_frame>16 weeks</time_frame>
    <description>Plasma levels of BNZ-1 will be measured after the 1st and last doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-dose and steady-state AUC</measure>
    <time_frame>16 weeks</time_frame>
    <description>Plasma levels of BNZ-1 will be measured after the 1st and last doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state Elimination half-life (t1/2)</measure>
    <time_frame>16 weeks</time_frame>
    <description>Plasma levels of BNZ-1 will be measured after the last dose</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory assessment of changes from baseline in CTCL disease severity (mSWAT)</measure>
    <time_frame>16 weeks</time_frame>
    <description>mSWAT</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory assessment of Complete Response in LGL</measure>
    <time_frame>16 weeks</time_frame>
    <description>Normalization of CBC and LGL count</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory assessment of Partial Response in LGL</measure>
    <time_frame>16 weeks</time_frame>
    <description>ANC: &gt;50% improvement from baseline and &gt;500 cells/uL; or &gt;50% reduction in transfusion requirements</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>LGL Leukemia</condition>
  <condition>CTCL</condition>
  <arm_group>
    <arm_group_label>BNZ-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV PEGylated BNZ132-1-40</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BNZ132-1-40</intervention_name>
    <description>Injectable PEGylated peptide antagonist that binds to the common gamma chain (γc) signaling receptor for the cytokines interleukin (IL)-2, IL-9, and IL-15</description>
    <arm_group_label>BNZ-1</arm_group_label>
    <other_name>BNZ-1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to consent and participate in the study.&#xD;
&#xD;
          -  Agrees not to receive any other investigational product or therapy while participating&#xD;
             in this study.&#xD;
&#xD;
          -  Must be:&#xD;
&#xD;
               -  Currently using two forms of effective birth control (one of which is a barrier&#xD;
                  method) for the duration of the study for both males and females of childbearing&#xD;
                  potential. Effective methods of birth control include hormonal contraception&#xD;
                  (i.e., birth control pills, injected hormones, vaginal ring), intrauterine&#xD;
                  device, or barrier methods with spermicide (i.e., diaphragm with spermicide,&#xD;
                  condom with spermicide), or&#xD;
&#xD;
               -  Surgically sterile (i.e., hysterectomy, tubal ligation, vasectomy).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.&#xD;
&#xD;
          -  Life expectancy &gt;1 year.&#xD;
&#xD;
        LGL-Specific:&#xD;
&#xD;
          -  Phenotypic studies (obtained within 8 weeks prior to study drug administration) from&#xD;
             peripheral blood showing CD3+, CD57+ cells &gt;400/mm³ or CD8+ cells &gt;650/mm³.&#xD;
&#xD;
               -  Note: Complete blood count (CBC) and differential should be reported for the&#xD;
                  phenotyped sample.&#xD;
&#xD;
          -  Evidence for clonal T-cell receptor gene rearrangement (obtained within 1 year prior&#xD;
             to study drug administration).&#xD;
&#xD;
        CTCL-Specific:&#xD;
&#xD;
          -  Histopathologically confirmed mycosis fungoides or Sézary syndrome (CTCL stage IIB or&#xD;
             greater according to the European Organization for Research and Treatment of&#xD;
             Cancer/International Society for Cutaneous Lymphomas [EORTC-ISCL] consensus&#xD;
             classification) at study entry with progressive, persistent, or recurrent disease who&#xD;
             have no available remaining standard therapeutic options (i.e., Refractory) as&#xD;
             determined by the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine,&#xD;
             renal, or other major systemic disease making implementation of the protocol or&#xD;
             interpretation of the study results difficult, or that would put the subject at risk&#xD;
             by participating in the study in the opinion of the Investigator.&#xD;
&#xD;
          -  History of or currently active primary or secondary immunodeficiency.&#xD;
&#xD;
          -  Known active bacterial, viral, fungal, mycobacterial infection, or other infection&#xD;
             (including tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal&#xD;
             infection of nail beds, minor upper respiratory tract infection, and minor skin&#xD;
             conditions]), or any major episode of infection that required hospitalization or&#xD;
             treatment with IV antibiotics within 30 days of study drug administration or oral&#xD;
             antibiotics within 14 days prior to study drug administration.&#xD;
&#xD;
          -  Received other investigational products or therapy in the 60 days prior to study drug&#xD;
             administration.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Brammer, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>10101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The James Cancer Center, Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Cancer Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <last_update_submitted>May 24, 2021</last_update_submitted>
  <last_update_submitted_qc>May 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BNZ-1</keyword>
  <keyword>Cytokine</keyword>
  <keyword>IL-2</keyword>
  <keyword>IL-15</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Large Granular Lymphocytic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>6 months after study data analysis is completed and a CSR has been generated</ipd_time_frame>
  </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/NCT03239392
org study id: BNZ1-CT-201
nct id: NCT03239392
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is an open-label, multi-center, dose-ranging study to characterize the safety,
      tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered
      weekly by IV infusion to adults diagnosed with Large Granular Lymphocyte (LGL) Leukemia or
      refractory Cutaneous T-cell Lymphoma (CTCL).
This study is an open-label, multi-center, dose-ranging study to characterize the safety,
      tolerability, preliminary efficacy, and PK/PD of up to four dose levels of BNZ-1 administered
      weekly by IV infusion to adults diagnosed with LGL or CTCL. The study has 5 periods:

        -  Screening Period

        -  4-week Treatment Period

        -  3-month Treatment Extension Period

        -  Long-term Extension Period (open-ended)

        -  6-week Follow-up Period Subjects will be screened for eligibility within 30 days of
           study Day 1 (first dosing day of the 4-Week Treatment Period).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence, severity and relationship of treatment-emergent adverse events
time frame: 1 month
measure: Incidence, severity and relationship of treatment-emergent adverse events
time frame: 4 months
measure: Pharmacodynamics
time frame: 16 weeks
description: Flow cytometry: Change from baseline over time for Tregs, NK cells and CD8+ central memory T-cells
measure: Single-dose and steady-state Cmax
time frame: 16 weeks
description: Plasma levels of BNZ-1 will be measured after the 1st and last doses
measure: Single-dose and steady-state AUC
time frame: 16 weeks
description: Plasma levels of BNZ-1 will be measured after the 1st and last doses
measure: Steady-state Elimination half-life (t1/2)
time frame: 16 weeks
description: Plasma levels of BNZ-1 will be measured after the last dose
measure: Exploratory assessment of changes from baseline in CTCL disease severity (mSWAT)
time frame: 16 weeks
description: mSWAT
measure: Exploratory assessment of Complete Response in LGL
time frame: 16 weeks
description: Normalization of CBC and LGL count
measure: Exploratory assessment of Partial Response in LGL
time frame: 16 weeks
description: ANC: >50% improvement from baseline and >500 cells/uL; or >50% reduction in transfusion requirements
arm group label: BNZ-1
arm group type: Experimental
description: IV PEGylated BNZ132-1-40
intervention type: Drug
intervention name: BNZ132-1-40
description: Injectable PEGylated peptide antagonist that binds to the common gamma chain (γc) signaling receptor for the cytokines interleukin (IL)-2, IL-9, and IL-15
arm group label: BNZ-1
other name: BNZ-1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jonathan Brammer, MD, PhD
role: Principal Investigator
affiliation: Ohio State University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Large Granular Lymphocytic
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: 6 months after study data analysis is completed and a CSR has been generated