<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/NCT04453085</url>
  </required_header>
  <id_info>
    <org_study_id>JR-171-102</org_study_id>
    <nct_id>NCT04453085</nct_id>
  </id_info>
  <brief_title>An Extension Study of JR-171-101 Study in Patients With MPS I</brief_title>
  <official_title>An Extension Study of JR-171-101 Study in Patients With Mucopolysaccharidosis Type I</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>JCR Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>JCR Pharmaceuticals Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Phase I/II, open label, multicenter, multinational (Japan, Brazil and the US) extension study&#xD;
      of JR-171-101 for the treatment of MPS I&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who have completed the Part2 of JR-171-101 study and fulfill all eligibility&#xD;
      criteria can be enrolled in this JR-171-102 study. Until the dose determination in the&#xD;
      JR-171-102 study, subjects will intravenously receive either low dose or high dose of JR-171&#xD;
      at the same doses received at Week 12 of the JR-171-101 study. Thereafter, all subjects will&#xD;
      be transitioned to the optimal dose determined based on the results of JR-171-101 study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 28, 2021</start_date>
  <completion_date type="Anticipated">April 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2025</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>156 weeks</time_frame>
    <description>Adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results</measure>
    <time_frame>156 weeks</time_frame>
    <description>Hematology</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results</measure>
    <time_frame>156 weeks</time_frame>
    <description>Biochemistry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results</measure>
    <time_frame>156 weeks</time_frame>
    <description>Serum iron tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results</measure>
    <time_frame>156 weeks</time_frame>
    <description>Urinalysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal vital signs</measure>
    <time_frame>156 weeks</time_frame>
    <description>Pulse rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal vital signs</measure>
    <time_frame>156 weeks</time_frame>
    <description>Body temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal vital signs</measure>
    <time_frame>156 weeks</time_frame>
    <description>Blood pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal vital signs</measure>
    <time_frame>156 weeks</time_frame>
    <description>Body weight</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal EKG readings</measure>
    <time_frame>156 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>156 weeks</time_frame>
    <description>Anti-human-α-L-iduronidase antibodies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>156 weeks</time_frame>
    <description>Anti-JR-171 antibodies</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>156 weeks</time_frame>
    <description>Infusion associated reaction (IAR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid</measure>
    <time_frame>Weeks 26, 52, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid</measure>
    <time_frame>Weeks 26, 52, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CSF opening pressure</measure>
    <time_frame>Weeks 26, 52, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Heparan Sulfate Levels in Urinary</measure>
    <time_frame>Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Dermatan Sulfate Levels in Urinary</measure>
    <time_frame>Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Heparan Sulfate Levels in Serum</measure>
    <time_frame>Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Dermatan Sulfate Levels in Serum</measure>
    <time_frame>Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Liver Volume</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Spleen Volume.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>Left ventricular posterior wall thickness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>interventricular septal thickness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>left ventricular mass index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>left ventricular ejection fraction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>left ventricular ejection fraction,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Echocardiography.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
    <description>E/A ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 6-minute Walk Test Distance.</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in cognitive age equivalent score of neurocognitive testing</measure>
    <time_frame>Weeks 52, 104, 156</time_frame>
    <description>Wechsler IQ test or the Bayley scales of infant and toddler development</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in outcome of adaptive behavioral function</measure>
    <time_frame>Weeks 52, 104, 156</time_frame>
    <description>Vineland adaptive behavior scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in outcome of the Brief Visuospatial Memory Test-Revised</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in outcome of the Hopkins Verbal Learning Test-Revised</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in outcome of the Test of Variables of Attention</measure>
    <time_frame>Weeks 13, 26, 52, 78, 104, 130, 156</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in outcome of the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)</measure>
    <time_frame>Weeks 13, 26, 52, 104 156</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Mucopolysaccharidosis I</condition>
  <arm_group>
    <arm_group_label>JR-171</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Until the dose determination, subjects will intravenously receive either the low dose or high dose of JR-171 (the same dose as at Week 12 of the JR-171-101 study). Thereafter, all subjects will receive the optimal dose of JR-171 determined based on the results of JR-171-101 study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JR-171 (lepunafusp alfa)</intervention_name>
    <description>JR-171 IV infusion</description>
    <arm_group_label>JR-171</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who have completed the Part 2 of JR-171-101 study&#xD;
&#xD;
          -  A patient from whom written informed consent can be obtained. If the patient is aged&#xD;
             under 18 years (20 years in case of Japan) at the time of assent or willingness to&#xD;
             participate in the study cannot be confirmed due to MPS I-related intellectual&#xD;
             disability, informed permission from the patient's legally acceptable representative&#xD;
             (e.g., his/her parents or guardians) need to be obtained instead of his/her consent.&#xD;
             Even in this case, written informed consent should be obtained from the patient,&#xD;
             wherever possible&#xD;
&#xD;
          -  Female patient or male patient whose co-partners is of child-bearing potential agree&#xD;
             to use a medically accepted, highly effective method of contraception, such as&#xD;
             spermatocidal gel plus condom, an intrauterine device or oral contraceptives until one&#xD;
             month after the final administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A patient who is unable to perform the study procedures, except for 6-minute walk&#xD;
             test, neurocognitive testing, BVMT-R, HVLT-R, and T.O.V.A.&#xD;
&#xD;
          -  Judged by the principal investigator or subinvestigator as being unable to undergo&#xD;
             lumbar puncture, including those who have difficulties in taking a position for lumbar&#xD;
             puncture due to joint contracture or those who are likely to experience difficulty&#xD;
             breathing during the lumbar puncture process&#xD;
&#xD;
          -  Judged by the principal investigator or subinvestigator to be ineligible to&#xD;
             participate in the study due to a history of a serious drug allergy or&#xD;
             hypersensitivity to any drugs&#xD;
&#xD;
          -  Otherwise judged by the principal investigator or subinvestigator to be ineligible to&#xD;
             participate in the study in consideration of patient's safety&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Genética e Erros Inatos do Metabolismo - IGEIM</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fukuoka Children's Hospital</name>
      <address>
        <city>Fukuoka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kokura Medical Center</name>
      <address>
        <city>Kitakyushu</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka Metropolitan University Hospital</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Japan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>December 12, 2022</last_update_submitted>
  <last_update_submitted_qc>December 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mucopolysaccharidosis I</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucopolysaccharidoses</mesh_term>
    <mesh_term>Mucopolysaccharidosis I</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/NCT04453085
org study id: JR-171-102
nct id: NCT04453085
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase I/II, open label, multicenter, multinational (Japan, Brazil and the US) extension study
      of JR-171-101 for the treatment of MPS I
Patients who have completed the Part2 of JR-171-101 study and fulfill all eligibility
      criteria can be enrolled in this JR-171-102 study. Until the dose determination in the
      JR-171-102 study, subjects will intravenously receive either low dose or high dose of JR-171
      at the same doses received at Week 12 of the JR-171-101 study. Thereafter, all subjects will
      be transitioned to the optimal dose determined based on the results of JR-171-101 study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with Adverse Events
time frame: 156 weeks
description: Adverse events
measure: Incidence of abnormal laboratory test results
time frame: 156 weeks
description: Hematology
measure: Incidence of abnormal laboratory test results
time frame: 156 weeks
description: Biochemistry
measure: Incidence of abnormal laboratory test results
time frame: 156 weeks
description: Serum iron tests
measure: Incidence of abnormal laboratory test results
time frame: 156 weeks
description: Urinalysis
measure: Incidence of abnormal vital signs
time frame: 156 weeks
description: Pulse rate
measure: Incidence of abnormal vital signs
time frame: 156 weeks
description: Body temperature
measure: Incidence of abnormal vital signs
time frame: 156 weeks
description: Blood pressure
measure: Incidence of abnormal vital signs
time frame: 156 weeks
description: Body weight
measure: Incidence of abnormal EKG readings
time frame: 156 weeks
measure: Number of participants with Adverse Events
time frame: 156 weeks
description: Anti-human-α-L-iduronidase antibodies
measure: Number of participants with Adverse Events
time frame: 156 weeks
description: Anti-JR-171 antibodies
measure: Number of participants with Adverse Events
time frame: 156 weeks
description: Infusion associated reaction (IAR)
measure: Change From Baseline in Heparan Sulfate Levels in Cerebrospinal Fluid
time frame: Weeks 26, 52, 104, 156
measure: Change From Baseline in Dermatan Sulfate Levels in Cerebrospinal Fluid
time frame: Weeks 26, 52, 104, 156
measure: CSF opening pressure
time frame: Weeks 26, 52, 104, 156
measure: Change From Baseline in Heparan Sulfate Levels in Urinary
time frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
measure: Change From Baseline in Dermatan Sulfate Levels in Urinary
time frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
measure: Change From Baseline in Heparan Sulfate Levels in Serum
time frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
measure: Change From Baseline in Dermatan Sulfate Levels in Serum
time frame: Weeks 13, 26, 39, 52, 65, 78, 91, 104, 130, 156
measure: Change From Baseline in Liver Volume
time frame: Weeks 13, 26, 52, 78, 104, 156
measure: Change From Baseline in Spleen Volume.
time frame: Weeks 13, 26, 52, 78, 104, 156
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: Left ventricular posterior wall thickness
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: interventricular septal thickness
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: left ventricular mass index
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: left ventricular ejection fraction
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: left ventricular ejection fraction,
measure: Change From Baseline in Echocardiography.
time frame: Weeks 13, 26, 52, 78, 104, 156
description: E/A ratio
measure: Change From Baseline in 6-minute Walk Test Distance.
time frame: Weeks 13, 26, 52, 78, 104, 156
measure: Changes from baseline in cognitive age equivalent score of neurocognitive testing
time frame: Weeks 52, 104, 156
description: Wechsler IQ test or the Bayley scales of infant and toddler development
measure: Changes from baseline in outcome of adaptive behavioral function
time frame: Weeks 52, 104, 156
description: Vineland adaptive behavior scales
measure: Changes from baseline in outcome of the Brief Visuospatial Memory Test-Revised
time frame: Weeks 13, 26, 52, 78, 104, 130, 156
measure: Changes from baseline in outcome of the Hopkins Verbal Learning Test-Revised
time frame: Weeks 13, 26, 52, 78, 104, 130, 156
measure: Changes from baseline in outcome of the Test of Variables of Attention
time frame: Weeks 13, 26, 52, 78, 104, 130, 156
measure: Changes from baseline in outcome of the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)
time frame: Weeks 13, 26, 52, 104 156
arm group label: JR-171
arm group type: Experimental
description: Until the dose determination, subjects will intravenously receive either the low dose or high dose of JR-171 (the same dose as at Week 12 of the JR-171-101 study). Thereafter, all subjects will receive the optimal dose of JR-171 determined based on the results of JR-171-101 study.
intervention type: Drug
intervention name: JR-171 (lepunafusp alfa)
description: JR-171 IV infusion
arm group label: JR-171
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
country: Japan
country: United States
responsible party type: Sponsor
mesh term: Mucopolysaccharidoses
mesh term: Mucopolysaccharidosis I
sharing ipd: No