xml: <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/NCT05967299</url>
    </required_header>
    <id_info>
      <org_study_id>10001522</org_study_id>
      <secondary_id>001522-H</secondary_id>
      <nct_id>NCT05967299</nct_id>
    </id_info>
    <brief_title>Study of Intravenous ZMA001 in Healthy Subjects</brief_title>
    <official_title>A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous ZMA001 in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Background:&#xD;
  &#xD;
        A number of diseases can cause a type of lung injury called pulmonary arterial hypertension&#xD;
        (PAH). Most people who develop PAH do not survive more than a few years. A new study drug&#xD;
        (ZMA001) may help. ZMA001 is a monoclonal antibody. This type of drug consists of proteins,&#xD;
        made in a facility, that are very similar to proteins in a human body. But before giving&#xD;
        ZMA001 to people sick with PAH, researchers want to find out how the drug affects healthy&#xD;
        people.&#xD;
  &#xD;
        Objective:&#xD;
  &#xD;
        To test a drug (ZMA001) in healthy volunteers.&#xD;
  &#xD;
        Eligibility:&#xD;
  &#xD;
        Healthy adults aged 18 to 60 years.&#xD;
  &#xD;
        Design:&#xD;
  &#xD;
        Participants will be screened. They will have a physical exam with blood tests. They will&#xD;
        have a urine test for drug use. They will have a test of their heart function.&#xD;
  &#xD;
        Participants will come to the clinic for 1 inpatient visit of up to 48 hours.&#xD;
  &#xD;
        ZMA001 is a liquid administered through a tube attached to a needle inserted into a vein in&#xD;
        the arm. Participants will receive this drug only once, during their inpatient stay. Some&#xD;
        participants will receive the drug; others will receive a placebo. A placebo is a treatment&#xD;
        that looks just like the real drug but contains no medicine. Participants will not know which&#xD;
        treatment they are getting.&#xD;
  &#xD;
        After a screening visit, participants will have 1 inpatient visit and up to 6 outpatient&#xD;
        visits over 16 weeks after receiving the treatment. Blood draws and other tests will be&#xD;
        repeated. Each outpatient visit is approximately 2 hours long.&#xD;
  &#xD;
        This study is the first time ZMA001 will be administered to people.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Description:&#xD;
  &#xD;
        ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated&#xD;
        monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery&#xD;
        pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH). The current&#xD;
        first-in-human, randomized, double-blind, placebo-controlled, single ascending-dose study&#xD;
        will determine the safety, tolerability, and pharmacokinetics of intravenous ZMA001 in&#xD;
        healthy subjects.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective: Safety and tolerability of ZMA001 in healthy subjects&#xD;
  &#xD;
        Secondary Objectives: Determine the pharmacokinetics of ZMA001 in healthy subjects following&#xD;
        a single, intravenous dose&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        Primary Endpoint: The number of all-cause, treatment-emergent adverse events, grade 1 and&#xD;
        above (following CTCAE v5.0 criteria) through day 113&#xD;
  &#xD;
        Secondary Endpoints: For each ZMA001 dose level (1.5, 5, 12 and 20 mg/kg), the following will&#xD;
        be determined [Timeframe: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8,&#xD;
        29, 57, 85 and 113]:&#xD;
  &#xD;
          1. Time to peak drug concentration (Tmax)&#xD;
  &#xD;
          2. Peak drug concentration (Cmax)&#xD;
  &#xD;
          3. Area under the drug concentration-time curve (AUC)&#xD;
  &#xD;
          4. Elimination half-life&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 21, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Safety and tolerability of ZMA001 in healthy subjects</measure>
      <time_frame>day 113</time_frame>
      <description>The number of all-cause, treatment-emergent adverse events, grade 1 and above (following CTCAE v5.0 criteria) through day 113</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.</measure>
      <time_frame>Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 29, 57, 85 and 113</time_frame>
      <description>For each ZMA001 dose level (1.5, 5, 12 and 20mg/kg), the following will be determined1. Time to peak drug concentration (Tmax)2. Peak drug concentration (Cmax)3. Area under the drug concentration-time curve(AUC)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">96</enrollment>
    <condition>Pulmonary Arterial Hypertension PAH</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo for ZMA001 is supplied in a single-use 10 mL glass vial. Each vial contains 30 mg/mL of sucrose.Placebo drug is manufactured using the same ingredients as active drug (20 mM histidine-HCl buffer [pH 5.6], 30 mg/mL sucrose, 0.070 w/v% polysorbate 80) excluding ZMA001 antibody and is packed in the same vial.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ZMA001 (BC-NKA-20008)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH).</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ZMA001 (BC-NKA-20008)</intervention_name>
      <description>ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH).</description>
      <arm_group_label>ZMA001 (BC-NKA-20008)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>30mg/ml Sucrose</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
          In order to be eligible to participate in this study, an individual must meet all of the&#xD;
          following criteria:&#xD;
  &#xD;
            1. Stated willingness to comply with all study procedures and availability for the&#xD;
               duration of the study&#xD;
  &#xD;
            2. Male* or female, aged 18 to 60 years, inclusive&#xD;
  &#xD;
            3. In good general health as evidenced by medical history&#xD;
  &#xD;
            4. Females of childbearing potential agree to use an accepted method of contraception&#xD;
               (see below) throughout study participation and for 120 days after study drug infusion.&#xD;
  &#xD;
            5. Males sexually active with a female partner must agree to use a condom with spermicide&#xD;
               for 120 days after study drug infusion or be surgically sterile for at least 90 days&#xD;
               before screening. Males must also agree to not donate sperm for 120 days after study&#xD;
               drug administration.&#xD;
  &#xD;
            6. Agreement to adhere to Lifestyle Considerations throughout study duration&#xD;
  &#xD;
            7. Ability of subject to understand and the willingness to sign a written informed&#xD;
               consent document.&#xD;
  &#xD;
                 -  Enrollment of healthy male subjects will be limited to no more than 14 out of the&#xD;
                    total study cohort of 32 in order to ensure an adequate representation of female&#xD;
                    subjects.&#xD;
  &#xD;
          Accepted methods of contraception for females of childbearing potential:&#xD;
  &#xD;
            -  Use of an implanted or intrauterine hormonal device for at least 30 consecutive days&#xD;
               before study drug infusion&#xD;
  &#xD;
            -  Use of oral, patch or injectable contraceptives or a vaginal hormonal device for at&#xD;
               least 30 consecutive days before study drug infusion&#xD;
  &#xD;
            -  Use of a non-hormonal intrauterine device for at least 30 consecutive days before&#xD;
               study drug infusion&#xD;
  &#xD;
            -  Two barrier methods such as a diaphragm with spermicide or a condom with spermicide&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
          An individual who meets any of the following criteria prior to informed consent will be&#xD;
          excluded from participation in this study:&#xD;
  &#xD;
            1. Pregnancy or lactation. Females of childbearing potential must have a negative serum&#xD;
               B-human chorionic gonadotropin test no more than 48 hours from study drug infusion.&#xD;
  &#xD;
            2. History of severe drug or excipient allergy or hypersensitivity&#xD;
  &#xD;
            3. Known allergy to any of the components of the investigational drug or placebo&#xD;
  &#xD;
            4. Recent infection or febrile illness within the past 14 days&#xD;
  &#xD;
            5. Treatment with another investigational drug within the past 30 days or 5 half-lives,&#xD;
               whichever is longer&#xD;
  &#xD;
            6. Any vaccination within the past 4 weeks or receipt of a live-attenuated vaccine within&#xD;
               the past 6 months&#xD;
  &#xD;
            7. Use of tobacco products within the past 3 months&#xD;
  &#xD;
            8. Recreational drug use within the past 6 months or positive urine drug screen at&#xD;
               Screening Visit&#xD;
  &#xD;
            9. History of alcohol abuse within the past 2 years&#xD;
  &#xD;
           10. History or current clinically significant medical illness including (but not limited&#xD;
               to) hematologic, oncologic, renal, endocrine, pulmonary, gastrointestinal,&#xD;
               cardiovascular, infectious, hepatic, dermatologic, psychiatric, neurologic, autoimmune&#xD;
               or allergic disease&#xD;
  &#xD;
           11. Use of prescription drugs (except contraceptives) within the past 7 days or 5&#xD;
               half-lives, whichever is longer. Common non-prescription medications such as (but not&#xD;
               limited to) acetaminophen, ibuprofen, or anti-histamines are allowed up to 24 hours&#xD;
               prior to dosing.&#xD;
  &#xD;
           12. Body mass index less than 17 or greater than 32 kg/m^2&#xD;
  &#xD;
           13. Clinically significant abnormal results on clinical blood testing completed at the&#xD;
               Screening Visit&#xD;
  &#xD;
           14. Electrocardiographic evidence of clinically relevant heart disease&#xD;
  &#xD;
           15. Use of vitamins, herbal supplements, or similar products within the past 2 weeks&#xD;
  &#xD;
           16. Blood donation equal to or above 500 mL within 2 months prior to dosing.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jason M Elinoff, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sandra Cooper Bennett, R.N.</last_name>
      <phone>(240) 328-0465</phone>
      <email>sandra.cooper@nih.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jason M Elinoff, M.D.</last_name>
      <phone>(301) 978-6468</phone>
      <email>elinoffj@mail.nih.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>NIH Clinical Center Office of Patient Recruitment (OPR)</last_name>
        <phone>800-411-1222</phone>
        <phone_ext>TTY dial 711</phone_ext>
        <email>ccopr@nih.gov</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001522-H.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>August 17, 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>human monoclonal antibody (IgG1)</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>.DSMP</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05967299
  org study id: 10001522
  secondary id: 001522-H
  nct id: NCT05967299
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  Background:
  
        A number of diseases can cause a type of lung injury called pulmonary arterial hypertension
        (PAH). Most people who develop PAH do not survive more than a few years. A new study drug
        (ZMA001) may help. ZMA001 is a monoclonal antibody. This type of drug consists of proteins,
        made in a facility, that are very similar to proteins in a human body. But before giving
        ZMA001 to people sick with PAH, researchers want to find out how the drug affects healthy
        people.
  
        Objective:
  
        To test a drug (ZMA001) in healthy volunteers.
  
        Eligibility:
  
        Healthy adults aged 18 to 60 years.
  
        Design:
  
        Participants will be screened. They will have a physical exam with blood tests. They will
        have a urine test for drug use. They will have a test of their heart function.
  
        Participants will come to the clinic for 1 inpatient visit of up to 48 hours.
  
        ZMA001 is a liquid administered through a tube attached to a needle inserted into a vein in
        the arm. Participants will receive this drug only once, during their inpatient stay. Some
        participants will receive the drug; others will receive a placebo. A placebo is a treatment
        that looks just like the real drug but contains no medicine. Participants will not know which
        treatment they are getting.
  
        After a screening visit, participants will have 1 inpatient visit and up to 6 outpatient
        visits over 16 weeks after receiving the treatment. Blood draws and other tests will be
        repeated. Each outpatient visit is approximately 2 hours long.
  
        This study is the first time ZMA001 will be administered to people.
  Study Description:
  
        ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated
        monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery
        pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH). The current
        first-in-human, randomized, double-blind, placebo-controlled, single ascending-dose study
        will determine the safety, tolerability, and pharmacokinetics of intravenous ZMA001 in
        healthy subjects.
  
        Objectives:
  
        Primary Objective: Safety and tolerability of ZMA001 in healthy subjects
  
        Secondary Objectives: Determine the pharmacokinetics of ZMA001 in healthy subjects following
        a single, intravenous dose
  
        Endpoints:
  
        Primary Endpoint: The number of all-cause, treatment-emergent adverse events, grade 1 and
        above (following CTCAE v5.0 criteria) through day 113
  
        Secondary Endpoints: For each ZMA001 dose level (1.5, 5, 12 and 20 mg/kg), the following will
        be determined [Timeframe: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8,
        29, 57, 85 and 113]:
  
          1. Time to peak drug concentration (Tmax)
  
          2. Peak drug concentration (Cmax)
  
          3. Area under the drug concentration-time curve (AUC)
  
          4. Elimination half-life
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: Safety and tolerability of ZMA001 in healthy subjects
  time frame: day 113
  description: The number of all-cause, treatment-emergent adverse events, grade 1 and above (following CTCAE v5.0 criteria) through day 113
  measure: Determine the pharmacokinetics of ZMA001 in healthy subjects following a single, intravenous dose.
  time frame: Pre-infusion, end of infusion, 2, 4, 8, 12, 24, and 48h; Days 8, 29, 57, 85 and 113
  description: For each ZMA001 dose level (1.5, 5, 12 and 20mg/kg), the following will be determined1. Time to peak drug concentration (Tmax)2. Peak drug concentration (Cmax)3. Area under the drug concentration-time curve(AUC)
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo for ZMA001 is supplied in a single-use 10 mL glass vial. Each vial contains 30 mg/mL of sucrose.Placebo drug is manufactured using the same ingredients as active drug (20 mM histidine-HCl buffer [pH 5.6], 30 mg/mL sucrose, 0.070 w/v% polysorbate 80) excluding ZMA001 antibody and is packed in the same vial.
  arm group label: ZMA001 (BC-NKA-20008)
  arm group type: Experimental
  description: ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH).
  intervention type: Drug
  intervention name: ZMA001 (BC-NKA-20008)
  description: ZMA001 is a fully human, monoclonal antibody (IgG1) that inhibits migration of activated monocytes and macrophages and reduces pulmonary vascular remodeling and pulmonary artery pressure in pre-clinical rodent models of pulmonary arterial hypertension (PAH).
  arm group label: ZMA001 (BC-NKA-20008)
  intervention type: Other
  intervention name: Placebo
  description: 30mg/ml Sucrose
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Jason M Elinoff, M.D.
  role: Principal Investigator
  affiliation: National Heart, Lung, and Blood Institute (NHLBI)
  last name: Sandra Cooper Bennett, R.N.
  phone: (240) 328-0465
  email: sandra.cooper@nih.gov
  last name: Jason M Elinoff, M.D.
  phone: (301) 978-6468
  email: elinoffj@mail.nih.gov
  facility: 
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001522-H.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Pulmonary Arterial Hypertension
  sharing ipd: Yes
  ipd description: .DSMP