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/NCT06041919</url>
    </required_header>
    <id_info>
      <org_study_id>RESP30X-EBA</org_study_id>
      <nct_id>NCT06041919</nct_id>
    </id_info>
    <brief_title>Evaluating the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Tuberculosis</brief_title>
    <official_title>A Phase 2 Study to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Nebulised RESP301 in Adults With Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Thirty Respiratory Limited</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Thirty Respiratory Limited</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A Phase 2, Single-Centre, Open-Label, Parallel Control Arm, Randomised Clinical Study to&#xD;
        Evaluate the Early Bactericidal Activity (EBA), Safety and Tolerability of Nebulised RESP301&#xD;
        in Adults with Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A total of approximately 15 participants will be recruited per treatment arm (total of&#xD;
        approximately 75 participants in the study). Control arm participants will be split across&#xD;
        sequential stages stages 1 and 2, with no stratification.&#xD;
  &#xD;
        Stage 1: To determine the EBA of&#xD;
  &#xD;
          -  Treatment Arm 1 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation&#xD;
             administered three times daily over 14 days&#xD;
  &#xD;
          -  Treatment Arm 2 (Control; n= 5) - HRZE taken orally once daily&#xD;
  &#xD;
        On completion of Stage 1, recruitment will be paused and an interim analysis performed to&#xD;
        determine whether the study should proceed to Stage 2.&#xD;
  &#xD;
        Stage 2: To determine the EBA of&#xD;
  &#xD;
          -  Treatment Arm 2 (Control; n= 10) - HRZE taken orally once daily&#xD;
  &#xD;
          -  Treatment Arm 3 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation&#xD;
             administered once daily over 14 days&#xD;
  &#xD;
          -  Treatment Arm 4 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation&#xD;
             administered twice daily over 14 days&#xD;
  &#xD;
          -  Treatment Arm 5 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation&#xD;
             administered three times daily in combination with HRZE taken orally once daily over 14&#xD;
             days&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 19, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Parallel control arm, randomised clinical study in two sequential stages, with no stratification</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Microbiology staff will be blinded to treatment allocation.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>To determine the Early Bactericidal Activity (EBA) of inhaled RESP301</measure>
      <time_frame>14 days</time_frame>
      <description>Overnight sputum collection from which viable mycobacteria in the sample is quantified as time to positivity (TTP)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To determine the Early Bactericidal Activity (EBA) of inhaled RESP301</measure>
      <time_frame>14 days</time_frame>
      <description>Overnight sputum collection from which viable mycobacteria in the sample is quantified as colony forming units (CFU)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To determine the safety and tolerability of inhaled RESP301</measure>
      <time_frame>2 months</time_frame>
      <description>Incidence of Treatment Emergent Adverse Events (TEAEs) will be presented by severity, drug relatedness, seriousness, leading to early withdrawal and leading to death.</description>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Rifampicin Susceptible Pulmonary Tuberculosis</condition>
    <arm_group>
      <arm_group_label>1 (Active)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Inhaled RESP301 6ml via nebulisation three times daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>2 (Control)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>HRZE taken orally once daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>3 (Active)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Inhaled RESP301 6 ml via nebulisation once daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>4 (Active)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Inhaled RESP301 6 ml via nebulisation twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>5 (Active)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RESP301</intervention_name>
      <description>Nitric Oxide agent</description>
      <arm_group_label>1 (Active)</arm_group_label>
      <arm_group_label>3 (Active)</arm_group_label>
      <arm_group_label>4 (Active)</arm_group_label>
      <arm_group_label>5 (Active)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>HRZE</intervention_name>
      <description>isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)</description>
      <arm_group_label>2 (Control)</arm_group_label>
      <arm_group_label>5 (Active)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Provide written, informed consent prior to all study-related procedures and agree to&#xD;
               undergo all study procedures&#xD;
  &#xD;
            -  Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive&#xD;
  &#xD;
            -  Newly diagnosed pulmonary TB&#xD;
  &#xD;
            -  Rifampicin susceptible pulmonary TB as determined by molecular testing&#xD;
  &#xD;
            -  Ability to produce an adequate volume of sputum as estimated from a pre-treatment&#xD;
               overnight sputum collection sample (estimated 10 ml or more)&#xD;
  &#xD;
            -  Spirometry performed during screening with a FEV1 of ≥ 40%&#xD;
  &#xD;
            -  Be of non-childbearing potential or willing to use effective methods of contraception&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  HIV positive AND CD4 &lt; 350 cells/mm3 OR are receiving antiviral therapy (ART)&#xD;
  &#xD;
            -  Methaemoglobin saturation (SpMet) &gt;3%&#xD;
  &#xD;
            -  Female participant who is pregnant or breast-feeding&#xD;
  &#xD;
            -  Participants planning to conceive a child within the anticipated period of study&#xD;
               participation and for at least 90 days after the last dose of IMP in the study&#xD;
  &#xD;
            -  Participation in other clinical studies with investigational agents within 8 weeks&#xD;
               prior to screening&#xD;
  &#xD;
            -  Treatment received for this episode of TB with any drug active against M.tb&#xD;
  &#xD;
            -  Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2&#xD;
               weeks prior to screening, or systemic corticosteroids for more than 7 days within 2&#xD;
               weeks prior to screening.&#xD;
  &#xD;
            -  Treatment with nitric oxide and other nitric oxide donor agents, phosphodiesterase&#xD;
               inhibitors and lung surfactant drugs, within 30 days prior to screening&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Inva Hoti, PhD</last_name>
      <phone>+44 (0) 1235 431 201</phone>
      <email>inva.hoti@30.technology</email>
    </overall_contact>
    <location>
      <facility>
        <name>TASK Clinical Research Centre</name>
        <address>
          <city>Cape Town</city>
          <state>Bellville</state>
          <zip>7531</zip>
          <country>South Africa</country>
        </address>
      </facility>
      <contact>
        <last_name>Lee-Ann Davids, MD</last_name>
        <phone>+27 21 917 1044</phone>
        <email>dr.lee-ann@task.org.za</email>
      </contact>
      <investigator>
        <last_name>Lee-Ann Davids, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>South Africa</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 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>Early Bactericidal Activity (EBA)</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tuberculosis</mesh_term>
      <mesh_term>Tuberculosis, Pulmonary</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>To be determined</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/NCT06041919
  org study id: RESP30X-EBA
  nct id: NCT06041919
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  A Phase 2, Single-Centre, Open-Label, Parallel Control Arm, Randomised Clinical Study to
        Evaluate the Early Bactericidal Activity (EBA), Safety and Tolerability of Nebulised RESP301
        in Adults with Newly Diagnosed, Rifampicin Susceptible Pulmonary Tuberculosis
  A total of approximately 15 participants will be recruited per treatment arm (total of
        approximately 75 participants in the study). Control arm participants will be split across
        sequential stages stages 1 and 2, with no stratification.
  
        Stage 1: To determine the EBA of
  
          -  Treatment Arm 1 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation
             administered three times daily over 14 days
  
          -  Treatment Arm 2 (Control; n= 5) - HRZE taken orally once daily
  
        On completion of Stage 1, recruitment will be paused and an interim analysis performed to
        determine whether the study should proceed to Stage 2.
  
        Stage 2: To determine the EBA of
  
          -  Treatment Arm 2 (Control; n= 10) - HRZE taken orally once daily
  
          -  Treatment Arm 3 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation
             administered once daily over 14 days
  
          -  Treatment Arm 4 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation
             administered twice daily over 14 days
  
          -  Treatment Arm 5 (Active; n = 15) - inhaled RESP301 6 ml dosed via nebulisation
             administered three times daily in combination with HRZE taken orally once daily over 14
             days
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel control arm, randomised clinical study in two sequential stages, with no stratification
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Microbiology staff will be blinded to treatment allocation.
  measure: To determine the Early Bactericidal Activity (EBA) of inhaled RESP301
  time frame: 14 days
  description: Overnight sputum collection from which viable mycobacteria in the sample is quantified as time to positivity (TTP)
  measure: To determine the Early Bactericidal Activity (EBA) of inhaled RESP301
  time frame: 14 days
  description: Overnight sputum collection from which viable mycobacteria in the sample is quantified as colony forming units (CFU)
  measure: To determine the safety and tolerability of inhaled RESP301
  time frame: 2 months
  description: Incidence of Treatment Emergent Adverse Events (TEAEs) will be presented by severity, drug relatedness, seriousness, leading to early withdrawal and leading to death.
  arm group label: 1 (Active)
  arm group type: Experimental
  description: Inhaled RESP301 6ml via nebulisation three times daily
  arm group label: 2 (Control)
  arm group type: Active Comparator
  description: HRZE taken orally once daily
  arm group label: 3 (Active)
  arm group type: Experimental
  description: Inhaled RESP301 6 ml via nebulisation once daily
  arm group label: 4 (Active)
  arm group type: Experimental
  description: Inhaled RESP301 6 ml via nebulisation twice daily
  arm group label: 5 (Active)
  arm group type: Experimental
  description: Inhaled RESP301 6 ml via nebulisation three times daily plus HRZE taken orally once dialy
  intervention type: Drug
  intervention name: RESP301
  description: Nitric Oxide agent
  arm group label: 1 (Active)
  arm group label: 3 (Active)
  arm group label: 4 (Active)
  arm group label: 5 (Active)
  intervention type: Drug
  intervention name: HRZE
  description: isoniazid 75 mg (H), rifampicin 150 mg (R), pyrazinamide 400 mg (Z), ethambutol 275 mg (E)
  arm group label: 2 (Control)
  arm group label: 5 (Active)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Inva Hoti, PhD
  phone: +44 (0) 1235 431 201
  email: inva.hoti@30.technology
  facility: 
  contact: 
  investigator: 
  country: South Africa
  responsible party type: Sponsor
  mesh term: Tuberculosis
  mesh term: Tuberculosis, Pulmonary
  sharing ipd: Undecided
  ipd description: To be determined