<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/NCT03233126</url>
  </required_header>
  <id_info>
    <org_study_id>KRN23-003</org_study_id>
    <nct_id>NCT03233126</nct_id>
  </id_info>
  <brief_title>A Study of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia</brief_title>
  <official_title>A Phase 3 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Postmarketing Study of KRN23 Switched From the Phase 3 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kyowa Kirin Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kyowa Kirin Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</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>
      Before switching to the post-marketing study:&#xD;
&#xD;
      To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks&#xD;
      in children with X-linked hypophosphatemic rickets/osteomalacia(XLH).&#xD;
&#xD;
      After switching to the post-marketing study:&#xD;
&#xD;
      To evaluate the safety and efficacy of KRN23, which is switched from the investigational&#xD;
      product to the post-marketing study drug, at the approved dose and dosing regimen in subjects&#xD;
      who continue treatment&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 6, 2017</start_date>
  <completion_date type="Actual">February 17, 2020</completion_date>
  <primary_completion_date type="Actual">February 17, 2020</primary_completion_date>
  <phase>Phase 3</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 subjects for each adverse events</measure>
    <time_frame>up to week 128</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of subjects for each adverse events</measure>
    <time_frame>up to week 128</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect to body temperature</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to pulse rate</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to respiratory rate</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to blood pressure</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to 12-Lead Electrocardiogram</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to Renal Ultrasound</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect to Echocardiogram</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum phosphorus concentration at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1,25(OH)2D at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alkaline phosphatase at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine phosphorus at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tubular reabsorption of phosphate at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TmP/GFR at each test time point</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in serum phosphorus</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in 1,25(OH)2D</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in alkaline phosphatase</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in urine phosphorus</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in tubular reabsorption of phosphate</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in TmP/GFR</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Radiographic Global Impression of Change(RGI-C) global score</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline on Rickets Severity Score (RSS) total score</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in the Six Minute Walk Test</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in height-for-age z-scores from baseline</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum KRN23 concentration</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-KRN23 antibody</measure>
    <time_frame>up to week 128</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>X-linked Hypophosphatemic Rickets/Osteomalacia</condition>
  <arm_group>
    <arm_group_label>KRN23</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KRN23</intervention_name>
    <description>Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86</description>
    <arm_group_label>KRN23</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1）Personally submitted voluntary written informed consent by a legally authorized&#xD;
        representative.If appropriate, written or verbal assent to participate in the study should&#xD;
        be obtained from patients.&#xD;
&#xD;
        2) Aged ≥ 1 and ≤12 years 3）Patients who have open growth plate 4）Willing to perform a&#xD;
        self-administration of KRN23 and available to perform a self-administration 5）Diagnosis of&#xD;
        XLH, and meeting any of the followings;&#xD;
&#xD;
          1. phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX)&#xD;
             mutation in either the patient or in a directly related family member with appropriate&#xD;
             X-linked inheritance&#xD;
&#xD;
          2. Serum intact FGF23 level at screening ≥ 30 pg/mL 6） Finding evidence of rickets or&#xD;
             clinical symptoms 7）Meeting all of following criteria for laboratory test related to&#xD;
             XLH;&#xD;
&#xD;
        a）Serum P: &lt; 3.0 mg/dL b）Serum Cr: Within the age-adjusted normal limits c）Serum 25(OH)D: ≥&#xD;
        16 ng/mL 8） For female patients who have reached menarche with child bearing potential; a&#xD;
        negative urine pregnancy test at screening 9）For female patients with child baring&#xD;
        potential, or male patients with reproductive capacity; willingness to use an acceptable&#xD;
        method of contraception while participating in the study 10） Willingness to provide access&#xD;
        to prior medical records to determine eligibility including data on imaging tests, blood&#xD;
        chemistry, diagnosis, medication, and surgical history 11） Willingness and ability to&#xD;
        cooperatively complete all study procedures, adhere to the visit schedule and follow the&#xD;
        investigator's instructions, as considered by the investigator or subinvestigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1）Height percentile &gt; 50% based on age-adjusted Japanese norms at screening 2）Use of&#xD;
        aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within&#xD;
        7 days prior to screening 3）Current or prior use of leuprorelin, triptorelin, goserelin, or&#xD;
        other drugs known to delay puberty 4）Use of growth hormone therapy within 12 months before&#xD;
        screening 5）Use of medication to suppress parathyroid hormone within 60 days prior to&#xD;
        screening 6）Serum calcium levels outside the age-adjusted normal limits 7）Intact&#xD;
        parathyroid hormone(iPTH) levels ≥ 163 pg/mL 8）Presence of nephrocalcinosis on renal&#xD;
        ultrasound grade 4 based on the following scale: 0 = Normal&#xD;
&#xD;
          1. = Faint hyperechogenic rim around the medullary pyramids&#xD;
&#xD;
          2. = More intense echogenic rim with echoes faintly filling the entire pyramid&#xD;
&#xD;
          3. = Uniformly intense echoes throughout the pyramid&#xD;
&#xD;
          4. = Stone formation: solitary focus of echoes at the tip of the pyramid 9）Planned or&#xD;
             recommended orthopedic surgery 10）Blood or blood product transfusion within 60 days&#xD;
             prior to screening 11）History of malignancy within 5 years prior to registration&#xD;
             12）History of being positive for human immunodeficiency virus antibody, hepatitis B&#xD;
             antigen and/or hepatitis C virus antibody 13）Predisposition to infection, or history&#xD;
             of recurrent infection or known immunodeficiency 14）Use of any investigational product&#xD;
             or investigational medical device within 4 months prior to screening, or requirement&#xD;
             for any investigational agent prior to completion of all scheduled study assessments&#xD;
             15）Receiving investigational agent in the UX023-CL301 study 16）Use of a therapeutic&#xD;
             monoclonal antibody other than KRN23 within 90 days prior to screening 17）History of&#xD;
             allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any&#xD;
             other monoclonal antibodies 18）Anyone otherwise considered unsuitable participation in&#xD;
             the study by the investigator or subinvestigator&#xD;
&#xD;
        Subjects eligible for enrollment in the post-marketing clinical study must meet both of the&#xD;
        following criteria:&#xD;
&#xD;
        1) Personally submitted voluntary written informed consent to participate in the&#xD;
        postmarketing clinical study by a legally authorized representative. If appropriate,&#xD;
        written or verbal assent to participate in the post-marketing clinical study should be&#xD;
        obtained from subjects.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center</name>
      <address>
        <city>Yokohama</city>
        <state>Kanagwa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Corporation Osaka University Hospital</name>
      <address>
        <city>Suita</city>
        <state>Osaka</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka Hospital, Japan Community Healthcare Organization (JCHO)</name>
      <address>
        <city>Ōsaka</city>
        <state>Osaka</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Okayama Saiseikai General Hospital Outpatient Center</name>
      <address>
        <city>Okayama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 11, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>August 31, 2022</last_update_submitted>
  <last_update_submitted_qc>August 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2022</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>Rickets</mesh_term>
    <mesh_term>Osteomalacia</mesh_term>
    <mesh_term>Rickets, Hypophosphatemic</mesh_term>
    <mesh_term>Familial Hypophosphatemic Rickets</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/NCT03233126
org study id: KRN23-003
nct id: NCT03233126
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Before switching to the post-marketing study:

      To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks
      in children with X-linked hypophosphatemic rickets/osteomalacia(XLH).

      After switching to the post-marketing study:

      To evaluate the safety and efficacy of KRN23, which is switched from the investigational
      product to the post-marketing study drug, at the approved dose and dosing regimen in subjects
      who continue treatment
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects for each adverse events
time frame: up to week 128
measure: Percentage of subjects for each adverse events
time frame: up to week 128
measure: Effect to body temperature
time frame: up to week 128
measure: Effect to pulse rate
time frame: up to week 128
measure: Effect to respiratory rate
time frame: up to week 128
measure: Effect to blood pressure
time frame: up to week 128
measure: Effect to 12-Lead Electrocardiogram
time frame: up to week 128
measure: Effect to Renal Ultrasound
time frame: up to week 128
measure: Effect to Echocardiogram
time frame: up to week 128
measure: Serum phosphorus concentration at each test time point
time frame: up to week 128
measure: 1,25(OH)2D at each test time point
time frame: up to week 128
measure: Alkaline phosphatase at each test time point
time frame: up to week 128
measure: Urine phosphorus at each test time point
time frame: up to week 128
measure: Tubular reabsorption of phosphate at each test time point
time frame: up to week 128
measure: TmP/GFR at each test time point
time frame: up to week 128
measure: Change from baseline in serum phosphorus
time frame: up to week 128
measure: Change from baseline in 1,25(OH)2D
time frame: up to week 128
measure: Change from baseline in alkaline phosphatase
time frame: up to week 128
measure: Change from baseline in urine phosphorus
time frame: up to week 128
measure: Change from baseline in tubular reabsorption of phosphate
time frame: up to week 128
measure: Change from baseline in TmP/GFR
time frame: up to week 128
measure: Improvement in Radiographic Global Impression of Change(RGI-C) global score
time frame: up to week 128
measure: Change from baseline on Rickets Severity Score (RSS) total score
time frame: up to week 128
measure: Change from baseline in the Six Minute Walk Test
time frame: up to week 128
measure: Change in height-for-age z-scores from baseline
time frame: up to week 128
measure: Serum KRN23 concentration
time frame: up to week 128
measure: Anti-KRN23 antibody
time frame: up to week 128
arm group label: KRN23
arm group type: Experimental
description: Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128
intervention type: Drug
intervention name: KRN23
description: Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86
arm group label: KRN23
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Rickets
mesh term: Osteomalacia
mesh term: Rickets, Hypophosphatemic
mesh term: Familial Hypophosphatemic Rickets
sharing ipd: No