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/NCT05987449</url>
    </required_header>
    <id_info>
      <org_study_id>WP44714</org_study_id>
      <secondary_id>2023-503906-35-00</secondary_id>
      <nct_id>NCT05987449</nct_id>
    </id_info>
    <brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A</brief_title>
    <official_title>A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hoffmann-La Roche</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Hoffmann-La Roche</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>
        Study WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter,&#xD;
        multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or&#xD;
        moderate hemophilia A with or without factor VIII (FVIII) inhibitors. The aim is to&#xD;
        investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and&#xD;
        efficacy of multiple ascending doses of NXT007.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 29, 2023</start_date>
    <completion_date type="Anticipated">June 16, 2032</completion_date>
    <primary_completion_date type="Anticipated">June 16, 2032</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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale</measure>
      <time_frame>From Baseline until study completion or discontinuation (up to 7.5 years)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters</measure>
      <time_frame>From Baseline until study completion or discontinuation (up to 7.5 years)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters</measure>
      <time_frame>From Baseline until study completion or discontinuation (up to 7.5 years)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants with at Least One Vital Sign Abnormality</measure>
      <time_frame>From Baseline until study completion or discontinuation (up to 7.5 years)</time_frame>
      <description>The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Participants with at Least One Abnormality on Electrocardiogram (ECG) Recordings</measure>
      <time_frame>From Baseline until study completion or discontinuation (up to 7.5 years)</time_frame>
      <description>The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF inteval.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Plasma Concentration of NXT007 at Specified Timepoints</measure>
      <time_frame>At prespecified timepoints from Day 1 to Day 155, and every 28 days from Day 169 until study completion (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose</measure>
      <time_frame>At prespecified timepoints from Day 1 to Day 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose</measure>
      <time_frame>At prespecified timepoints from Day 1 to Day 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose</measure>
      <time_frame>At prespecified timepoints from Day 1 to Day 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug</measure>
      <time_frame>Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug</measure>
      <time_frame>Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Model-Based Annualized Bleeding Rate for Treated Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Calculated Annualized Bleeding Rate for Treated Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Calculated Annualized Bleeding Rate for Treated Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Model-Based Annualized Bleeding Rate for All Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Calculated Annualized Bleeding Rate for All Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Calculated Annualized Bleeding Rate for All Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Model-Based Annualized Bleeding Rate for Treated Joint Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds</measure>
      <time_frame>From first dose of study drug until study completion or discontinuation (up to 7.5 years)</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Hemophilia A</condition>
    <arm_group>
      <arm_group_label>NXT007 Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NXT007</intervention_name>
      <description>Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.</description>
      <arm_group_label>NXT007 Dose Escalation</arm_group_label>
      <other_name>RO7589655</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Body weight ≥40 kilograms (kg) at screening&#xD;
  &#xD;
            -  Diagnosis of severe (Factor VIII [FVIII] coagulant activity &lt;1 IU/dL) or moderate&#xD;
               (FVIII coagulant activity ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or&#xD;
               without inhibitors against FVIII&#xD;
  &#xD;
            -  Participants with FVIII inhibitors: participants using recombinant activated factor&#xD;
               VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the&#xD;
               treatment of breakthrough bleeds, trauma, or procedures&#xD;
  &#xD;
            -  Historic local FVIII inhibitor test results being available during screening to&#xD;
               confirm any previous inhibitor history and current status&#xD;
  &#xD;
            -  Participants who previously successfully completed immune tolerance induction (ITI)&#xD;
               must have done so at least 5 years before screening and must have no evidence of&#xD;
               inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as &lt;0.6&#xD;
               Bethesda unit (BU)/mL (&lt;1.0 BU/mL only for laboratories with an historical sensitivity&#xD;
               cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery &gt;66%&#xD;
  &#xD;
            -  Documentation of number and type of bleeding episodes in the last 24 weeks prior to&#xD;
               enrollment&#xD;
  &#xD;
            -  Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and&#xD;
               hemoglobin ≥11 g/dL at the time of screening&#xD;
  &#xD;
            -  Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of&#xD;
               normal (ULN) (excluding Gilbert syndrome) and both AST and ALT ≤3× age-adapted ULN at&#xD;
               the time of screening, and no clinical signs or known laboratory/radiographic evidence&#xD;
               consistent with cirrhosis&#xD;
  &#xD;
            -  Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and&#xD;
               calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula&#xD;
  &#xD;
            -  Willingness and ability to comply with schedules visits, treatment plans, laboratory&#xD;
               tests, and other study procedures&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inherited or acquired bleeding disorders other than congenital hemophilia A&#xD;
  &#xD;
            -  Ongoing or planned ITI therapy&#xD;
  &#xD;
            -  Previous or current treatment for thromboembolic disease (with the exception of&#xD;
               previous catheter-associated thrombosis for which anti-thrombotic treatment is not&#xD;
               currently ongoing) or signs of thromboembolic disease&#xD;
  &#xD;
            -  At high risk for thrombotic microangiopathy (TMA), including past personal or family&#xD;
               history of TMA, in the investigator's judgment&#xD;
  &#xD;
            -  Personal history of ischemic heart disease, cerebrovascular disease, or diabetes&#xD;
               mellitus&#xD;
  &#xD;
            -  Strong family history of ischemic heart disease or cerebrovascular disease (i.e.,&#xD;
               first degree relatives such as parents, full siblings, or children): male relatives&#xD;
               diagnosed under the age of 55 years, females under the age of 65 years&#xD;
  &#xD;
            -  Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and&#xD;
               other systemic inflammatory disorders) that may currently increase the risk of&#xD;
               bleeding or thrombosis&#xD;
  &#xD;
            -  History of clinically significant allergies&#xD;
  &#xD;
            -  Previous or concomitant malignancies or leukemia&#xD;
  &#xD;
            -  Receipt of any of the following:&#xD;
  &#xD;
               i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5&#xD;
               half-lives of last drug administration or normalization of targeted parameters (e.g.,&#xD;
               anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug&#xD;
               within last 30 days or 5 half-lives, whichever is shorter; iii) Any other&#xD;
               investigational drug currently being administered or planned to be administered; iv)&#xD;
               Prior gene therapy or gene therapy planned to be administered.&#xD;
  &#xD;
            -  Protein C activity, protein S free antigen, or anti-thrombin III activity levels below&#xD;
               the lower limit of the reference range at screening&#xD;
  &#xD;
            -  Known HIV infection with CD4 counts &lt;200 cells/μL&#xD;
  &#xD;
            -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy&#xD;
               and to chimeric or humanized antibodies or fusion proteins&#xD;
  &#xD;
            -  Known hypersensitivity to Chinese hamster ovary cell products or to excipient content&#xD;
  &#xD;
            -  History or presence of an abnormal ECG that is deemed clinically significant, (e.g.,&#xD;
               complete left bundle branch block, second- or third -degree atrioventricular heart&#xD;
               block), including atrial fibrillation or evidence of prior myocardial infarction&#xD;
  &#xD;
            -  QT interval corrected through use of Fridericia's formula (QTcF) &gt;450 ms demonstrated&#xD;
               by at least two ECGs &gt;30 minutes apart&#xD;
  &#xD;
            -  History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such&#xD;
               as structural heart disease (e.g., severe left ventricular systolic dysfunction, left&#xD;
               ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia&#xD;
               demonstrated by diagnostic testing), clinically significant electrolyte abnormalities&#xD;
               (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden&#xD;
               unexplained death or long QT syndrome&#xD;
  &#xD;
            -  Current treatment with medications that are well known to prolong the QT interval&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>59 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Clinical Trials</last_name>
      <role>Study Director</role>
      <affiliation>Hoffmann-La Roche</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Reference Study ID Number: WP44714 https://forpatients.roche.com/</last_name>
      <phone>888-662-6728 (U.S. Only)</phone>
      <email>global-roche-genentech-trials@gene.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Auckland Cancer Trial Centre; Ward 64, Auckland City Hospital,</name>
        <address>
          <city>Auckland</city>
          <zip>1023</zip>
          <country>New Zealand</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>New Zealand</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hemophilia A</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).&#xD;
  Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).</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/NCT05987449
  org study id: WP44714
  secondary id: 2023-503906-35-00
  nct id: NCT05987449
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  Study WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter,
        multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or
        moderate hemophilia A with or without factor VIII (FVIII) inhibitors. The aim is to
        investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and
        efficacy of multiple ascending doses of NXT007.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale
  time frame: From Baseline until study completion or discontinuation (up to 7.5 years)
  measure: Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters
  time frame: From Baseline until study completion or discontinuation (up to 7.5 years)
  measure: Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters
  time frame: From Baseline until study completion or discontinuation (up to 7.5 years)
  measure: Number of Participants with at Least One Vital Sign Abnormality
  time frame: From Baseline until study completion or discontinuation (up to 7.5 years)
  description: The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
  measure: Number of Participants with at Least One Abnormality on Electrocardiogram (ECG) Recordings
  time frame: From Baseline until study completion or discontinuation (up to 7.5 years)
  description: The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF inteval.
  measure: Plasma Concentration of NXT007 at Specified Timepoints
  time frame: At prespecified timepoints from Day 1 to Day 155, and every 28 days from Day 169 until study completion (up to 7.5 years)
  measure: Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose
  time frame: At prespecified timepoints from Day 1 to Day 15
  measure: Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose
  time frame: At prespecified timepoints from Day 1 to Day 15
  measure: Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose
  time frame: At prespecified timepoints from Day 1 to Day 15
  measure: Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug
  time frame: Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug
  time frame: Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Model-Based Annualized Bleeding Rate for Treated Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Mean Calculated Annualized Bleeding Rate for Treated Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Median Calculated Annualized Bleeding Rate for Treated Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Model-Based Annualized Bleeding Rate for All Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Mean Calculated Annualized Bleeding Rate for All Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Median Calculated Annualized Bleeding Rate for All Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  measure: Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
  time frame: From first dose of study drug until study completion or discontinuation (up to 7.5 years)
  arm group label: NXT007 Dose Escalation
  arm group type: Experimental
  intervention type: Drug
  intervention name: NXT007
  description: Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.
  arm group label: NXT007 Dose Escalation
  other name: RO7589655
  criteria: 
  gender: Male
  minimum age: 12 Years
  maximum age: 59 Years
  healthy volunteers: No
  last name: Clinical Trials
  role: Study Director
  affiliation: Hoffmann-La Roche
  last name: Reference Study ID Number: WP44714 https://forpatients.roche.com/
  phone: 888-662-6728 (U.S. Only)
  email: global-roche-genentech-trials@gene.com
  facility: 
  status: Recruiting
  country: New Zealand
  responsible party type: Sponsor
  mesh term: Hemophilia A
  sharing ipd: No
  ipd description: For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
  Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).