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/NCT06015750</url>
    </required_header>
    <id_info>
      <org_study_id>D8400C00001</org_study_id>
      <secondary_id>2022-502793-17</secondary_id>
      <nct_id>NCT06015750</nct_id>
    </id_info>
    <brief_title>Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia</brief_title>
    <acronym>RESTORE</acronym>
    <official_title>An Interventional, Prospective Open-Label Study of Immunosuppressive Therapies to Mitigate Immune-Mediated Loss of Therapeutic Response to Asfotase Alfa (STRENSIQ®) for Hypophosphatasia (RESTORE)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Alexion</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Alexion</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>
        The primary objective of this study is to evaluate the effect of immunosuppressive therapy&#xD;
        (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of&#xD;
        effectiveness (LoE).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 29, 2023</start_date>
    <completion_date type="Anticipated">August 27, 2027</completion_date>
    <primary_completion_date type="Anticipated">August 27, 2027</primary_completion_date>
    <phase>Phase 4</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>Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100</measure>
      <time_frame>Week 100</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)</measure>
      <time_frame>Baseline Through Week 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ADA and NAb Titer Levels</measure>
      <time_frame>Baseline Through Week 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)</measure>
      <time_frame>Baseline Through Week 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)</measure>
      <time_frame>Baseline Through Week 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma Concentration of Inorganic Pyrophosphates (PPi)</measure>
      <time_frame>Baseline Through Week 100</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events</measure>
      <time_frame>Baseline Through Week 104</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">8</enrollment>
    <condition>Hypophosphatasia</condition>
    <arm_group>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>methotrexate</intervention_name>
      <description>Methotrexate will be administered SC or orally weekly for 104 weeks.</description>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>rituximab</intervention_name>
      <description>Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.</description>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>bortezomib</intervention_name>
      <description>Bortezomib will be administered via IV bolus or SC, as needed.</description>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IVIg</intervention_name>
      <description>IVIg will be administered via IV monthly through initial 74 weeks.</description>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Folic Acid</intervention_name>
      <description>Folic acid will be given orally as long as methotrexate is being dosed.</description>
      <arm_group_label>Pediatric participants with HPP</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Reoccurrence or worsening of rickets for at least the past 3 months in participants&#xD;
               who showed an initial efficacy response to asfotase alfa after at least 6 months of&#xD;
               continuous treatment and currently receiving asfotase alfa. RSS will be used to&#xD;
               determine severity at Baseline.&#xD;
  &#xD;
            -  Presence of ADAs, with or without NAbs, irrespective of their titers.&#xD;
  &#xD;
            -  Confirmation by the TMB that both the clinical evidence and immunogenicity-mediated&#xD;
               association noted above are present.&#xD;
  &#xD;
            -  Female participants of childbearing potential and male participants with partners of&#xD;
               childbearing potential must follow protocol-specified contraception guidance as&#xD;
               described in Section 10.5.&#xD;
  &#xD;
            -  Participant, or participant's legal guardian, is capable of signing informed consent&#xD;
               or assent as described in Section 10.1.3, which includes compliance with the&#xD;
               requirements and restrictions listed in the informed consent or assent form and in&#xD;
               this protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known history of human immunodeficiency virus (HIV) infection (evidenced by HIV type 1&#xD;
               or type 2 [HIV 1, HIV 2] antibody) or hepatitis B or C viral infection.&#xD;
  &#xD;
            -  Known or suspected history of drug or alcohol abuse or dependence within 1 year prior&#xD;
               to Screening.&#xD;
  &#xD;
            -  Inability of the participant, or the participant's legal guardian, to provide informed&#xD;
               consent.&#xD;
  &#xD;
            -  Pregnant, breastfeeding, or intending to conceive during the course of the study.&#xD;
  &#xD;
            -  Inability to travel to the clinic for specified visits during the Treatment Period&#xD;
               caused by disease per se or logistics (does not apply to external travel&#xD;
               restrictions).&#xD;
  &#xD;
            -  The participant is at risk of reactivation or has an active significant viral&#xD;
               infection such as hepatitis B, cytomegalovirus, herpes simplex, human polyomavirus&#xD;
               (also known as John Cunningham [JC] virus), parvovirus, or Epstein Barr virus.&#xD;
  &#xD;
            -  The participant is at risk of reactivation of tuberculosis or has regular contact (eg,&#xD;
               in the household) with individuals who are being actively treated for tuberculosis.&#xD;
  &#xD;
            -  The participant has had or is required to have any live vaccination within 1 month&#xD;
               prior to enrollment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>2 Years</minimum_age>
      <maximum_age>18 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>AstraZeneca Clinical Study Information Center</last_name>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Hypophosphatasia</keyword>
    <keyword>HPP</keyword>
    <keyword>Asfotase alfa</keyword>
    <keyword>Strensiq</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypophosphatasia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Folic Acid</mesh_term>
      <mesh_term>Rituximab</mesh_term>
      <mesh_term>Methotrexate</mesh_term>
      <mesh_term>Bortezomib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    </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/NCT06015750
  org study id: D8400C00001
  secondary id: 2022-502793-17
  nct id: NCT06015750
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary objective of this study is to evaluate the effect of immunosuppressive therapy
        (IST) in participants treated with asfotase alfa who demonstrate immune-mediated loss of
        effectiveness (LoE).
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Participants Who Achieve Immunosuppressive Therapy (IST) Complete Response at Week 100
  time frame: Week 100
  measure: Number Participants with Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
  time frame: Baseline Through Week 100
  measure: ADA and NAb Titer Levels
  time frame: Baseline Through Week 100
  measure: Serum Concentration of Asofatase Alfa (Measured as Enzyme Activity)
  time frame: Baseline Through Week 100
  measure: Plasma Concentration of Pyridoxal-5ˈ-Phosphate (PLP)
  time frame: Baseline Through Week 100
  measure: Plasma Concentration of Inorganic Pyrophosphates (PPi)
  time frame: Baseline Through Week 100
  measure: Number of Participants with Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
  time frame: Baseline Through Week 104
  arm group label: Pediatric participants with HPP
  arm group type: Experimental
  description: Pediatric participants who have been receiving asfotase alfa treatment for their HPP, and who demonstrate immune-mediated LoE.
  intervention type: Drug
  intervention name: methotrexate
  description: Methotrexate will be administered SC or orally weekly for 104 weeks.
  arm group label: Pediatric participants with HPP
  intervention type: Drug
  intervention name: rituximab
  description: Rituximab will be administered intravenously (IV) continuously weekly, for up to 74 weeks.
  arm group label: Pediatric participants with HPP
  intervention type: Drug
  intervention name: bortezomib
  description: Bortezomib will be administered via IV bolus or SC, as needed.
  arm group label: Pediatric participants with HPP
  intervention type: Drug
  intervention name: IVIg
  description: IVIg will be administered via IV monthly through initial 74 weeks.
  arm group label: Pediatric participants with HPP
  intervention type: Drug
  intervention name: Folic Acid
  description: Folic acid will be given orally as long as methotrexate is being dosed.
  arm group label: Pediatric participants with HPP
  criteria: 
  gender: All
  minimum age: 2 Years
  maximum age: 18 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
  responsible party type: Sponsor
  mesh term: Hypophosphatasia
  mesh term: Folic Acid
  mesh term: Rituximab
  mesh term: Methotrexate
  mesh term: Bortezomib
  sharing ipd: Yes
  ipd description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Clinical Study Report (CSR)