<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/NCT03815396</url>
  </required_header>
  <id_info>
    <org_study_id>Ph1 INBRX-101</org_study_id>
    <nct_id>NCT03815396</nct_id>
  </id_info>
  <brief_title>Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency</brief_title>
  <acronym>rhAAT-Fc</acronym>
  <official_title>An Open-Label, Multicenter, Phase 1 Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Intravenous Doses of Inhibrx rhAAT-Fc (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency (AATD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Inhibrx, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Inhibrx, Inc.</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>
      This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1&#xD;
      will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will&#xD;
      consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing&#xD;
      schedule is IV every 3 to 4 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 19, 2019</start_date>
  <completion_date type="Actual">August 18, 2022</completion_date>
  <primary_completion_date type="Actual">August 18, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of adverse events of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of adverse events of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration time curve (AUC) of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Area under the serum concentration time curve (AUC) of INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed serum concentration (Cmax) of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough observed serum concentration (Ctrough) of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Trough observed serum concentration (Cmax) of INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Time to Cmax (Tmax) of INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (T1/2) of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Half-life of INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of INBRX-101</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>The concentration of INBRX-101 in bronchoalveolar lavage fluid (BALF) be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional concentration of INBRX-101 in serum and BALF</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>The functional concentration of INBRX-101 in serum and BALF will be determined.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Alpha-1 Antitrypsin Deficiency</condition>
  <condition>AATD</condition>
  <arm_group>
    <arm_group_label>Part 1 Single Ascending Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Multiple Ascending Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INBRX-101/rhAAT-Fc</intervention_name>
    <description>INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).</description>
    <arm_group_label>Part 1 Single Ascending Dose</arm_group_label>
    <arm_group_label>Part 2 Multiple Ascending Dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented alpha-1 antitrypsin (AAT) serum concentration &lt;11 μM.&#xD;
&#xD;
          -  Diagnosis of alpha-1 antitrypsin deficiency (AATD) with any allelic combination with&#xD;
             exception of the null/null genotype.&#xD;
&#xD;
          -  For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: post-bronchodilator FEV1 of at&#xD;
             least 40% of predicted normal value.&#xD;
&#xD;
          -  For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: subjects eligible for&#xD;
             bronchoscopy per judgment of investigator.&#xD;
&#xD;
          -  Nonsmoker for at least 6 months prior to study and must remain nonsmoking for the&#xD;
             entire study duration.&#xD;
&#xD;
          -  Adequate hepatic and renal function as defined per protocol.&#xD;
&#xD;
          -  Willing to undergo current augmentation therapy washout (if applicable) and refrain&#xD;
             from initiating augmentation therapy, other investigational drug trials for AATD,&#xD;
             therapy with IV immunoglobulins or monoclonal antibodies during the entire study,&#xD;
             including follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known or suspected allergy to components of INBRX-101 (AAT or human IgG) or pdAAT.&#xD;
&#xD;
          -  Participation in any investigational drug trial within 30 days prior to this trial, or&#xD;
             subjects receiving IV immunoglobulins or monoclonal antibodies within 30 days prior to&#xD;
             this trial.&#xD;
&#xD;
          -  History of and/or on the waiting list for lung or liver transplant, lobectomy, or lung&#xD;
             volume reduction surgery.&#xD;
&#xD;
          -  Acute respiratory tract infection or COPD exacerbation that required antibiotic&#xD;
             treatment and/or increase in systemic steroid dosage within the 4 weeks prior to&#xD;
             screening. Subjects are permitted to continue to receive steroids if the investigator&#xD;
             judges the subject to have a history of stable dosing.&#xD;
&#xD;
          -  Subjects with ongoing or history of unstable cor pulmonale.&#xD;
&#xD;
          -  Infection with hepatitis A, B, or C or human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Active autoimmune disease or documented history of autoimmune disease that 1) required&#xD;
             systemic steroids or immune-suppressive medications and 2) tested positive for&#xD;
             auto-antibodies. Exception: Endocrinopathies managed with hormone replacement therapy&#xD;
             (HRT).&#xD;
&#xD;
          -  Current substance and/or alcohol abuse with protocol defined exceptions.&#xD;
&#xD;
          -  Current narcotics abuse with protocol defined exceptions.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vasily Andrianov, MD</last_name>
    <role>Study Director</role>
    <affiliation>Inhibrx, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC Davis School of Medicine</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hannibal Clinic</name>
      <address>
        <city>Hannibal</city>
        <state>Missouri</state>
        <zip>63401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The New Zealand Respiratory and Sleep Institute</name>
      <address>
        <city>Auckland</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Clinical Studies Trust Ltd</name>
      <address>
        <city>Christchurch</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waikato Respiratory and Gastro Research Unit</name>
      <address>
        <city>Hamilton</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cambridge</name>
      <address>
        <city>Cambridge</city>
        <state>East Of England</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B15 2GW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>September 9, 2022</last_update_submitted>
  <last_update_submitted_qc>September 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alpha-1 antitrypsin deficiency</keyword>
  <keyword>AATD</keyword>
  <keyword>alpha-1 disease</keyword>
  <keyword>AAT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alpha 1-Antitrypsin Deficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03815396
org study id: Ph1 INBRX-101
nct id: NCT03815396
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1
      will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will
      consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing
      schedule is IV every 3 to 4 weeks.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of adverse events of INBRX-101
time frame: Up to 7 months
description: Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
measure: Severity of adverse events of INBRX-101
time frame: Up to 7 months
description: Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
measure: Area under the serum concentration time curve (AUC) of INBRX-101
time frame: Up to 7 months
description: Area under the serum concentration time curve (AUC) of INBRX-101 will be determined.
measure: Maximum observed serum concentration (Cmax) of INBRX-101
time frame: Up to 7 months
description: Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.
measure: Trough observed serum concentration (Ctrough) of INBRX-101
time frame: Up to 7 months
description: Trough observed serum concentration (Cmax) of INBRX-101 will be determined.
measure: Time to Cmax (Tmax) of INBRX-101
time frame: Up to 7 months
description: Time to Cmax (Tmax) of INBRX-101 will be determined.
measure: Half-life (T1/2) of INBRX-101
time frame: Up to 7 months
description: Half-life of INBRX-101 will be determined.
measure: Immunogenicity of INBRX-101
time frame: Up to 7 months
description: Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.
measure: Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)
time frame: Up to 7 months
description: The concentration of INBRX-101 in bronchoalveolar lavage fluid (BALF) be determined.
measure: Functional concentration of INBRX-101 in serum and BALF
time frame: Up to 7 months
description: The functional concentration of INBRX-101 in serum and BALF will be determined.
arm group label: Part 1 Single Ascending Dose
arm group type: Experimental
description: INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).
arm group label: Part 2 Multiple Ascending Dose
arm group type: Experimental
description: INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).
intervention type: Drug
intervention name: INBRX-101/rhAAT-Fc
description: INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).
arm group label: Part 1 Single Ascending Dose
arm group label: Part 2 Multiple Ascending Dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Vasily Andrianov, MD
role: Study Director
affiliation: Inhibrx, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: New Zealand
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Alpha 1-Antitrypsin Deficiency
sharing ipd: No