<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/NCT02235493</url>
  </required_header>
  <id_info>
    <org_study_id>ALX-HPP-502s</org_study_id>
    <nct_id>NCT02235493</nct_id>
  </id_info>
  <brief_title>Non-interventional Substudy of ALX-HPP-502 to Assess Natural History of Patients With Juvenile-onset HPP Who Served as Historical Controls in ENB-006-09</brief_title>
  <official_title>A Single-Center, Non-interventional Substudy of ALX-HPP-502 to Assess Functional Natural History Data of Patients With Juvenile Historical Controls in ENB-006-09</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to characterize the natural history of HPP in patients with&#xD;
      Juvenile-onset HPP who served as historical controls in ENB-006-09.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease&#xD;
      characterized by defective bone mineralization and impaired phosphate and calcium regulation&#xD;
      that can lead to progressive damage to multiple vital organs, including destruction and&#xD;
      deformity of bones, profound muscle weakness, seizures, impaired renal function, and&#xD;
      respiratory failure. There are no approved disease-modifying treatments for patients with&#xD;
      this disease. There is also limited data available on the natural course of this disease over&#xD;
      time, particularly in patients with the juvenile-onset form.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall</measure>
    <time_frame>The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.</time_frame>
    <description>The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall</measure>
    <time_frame>The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.</time_frame>
    <description>The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">6</enrollment>
  <condition>Hypophosphatasia</condition>
  <condition>Bone Disease</condition>
  <arm_group>
    <arm_group_label>Retrospective Case Only</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Retrospective Case Only</intervention_name>
    <arm_group_label>Retrospective Case Only</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patient has juvenile-onset HPP and was selected as a historical-control for Study&#xD;
        ENB-006-09.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented informed consent/assent prior to video collection and data abstraction.&#xD;
&#xD;
          -  Documented informed consent/assent in Study ALX-HPP-502.&#xD;
&#xD;
          -  Patients with juvenile-onset HPP and was selected as a historical-control for Study&#xD;
             ENB-006-09.&#xD;
&#xD;
          -  Patients with at least 2 videos of basic mobility that were recorded at 2 different&#xD;
             clinic visits when the patient was ≥5 to ≤15 ye&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  There are no exclusion criteria for this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.hypophosphatasia.com</url>
    <description>Hypophosphatasia Website</description>
  </link>
  <link>
    <url>http://www.hypophosphatasia.com/hcp/</url>
    <description>Hypophosphatasia Website for Health Care Professionals</description>
  </link>
  <link>
    <url>http://www.magicfoundation.org</url>
    <description>HPP support group</description>
  </link>
  <link>
    <url>http://www.softbones.org</url>
    <description>US Hypophosphatasia Group (Soft Bones)</description>
  </link>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>August 25, 2015</results_first_submitted>
  <results_first_submitted_qc>August 25, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 28, 2015</results_first_posted>
  <last_update_submitted>March 11, 2019</last_update_submitted>
  <last_update_submitted_qc>March 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HPP</keyword>
  <keyword>Soft Bones</keyword>
  <keyword>low Alkaline Phosphatase</keyword>
  <keyword>genetic metabolic disorder</keyword>
  <keyword>alkaline phosphatase</keyword>
  <keyword>tissue non-specific alkaline phosphatase</keyword>
  <keyword>rickets</keyword>
  <keyword>osteomalacia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bone Diseases</mesh_term>
    <mesh_term>Hypophosphatasia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Retrospective Observational</title>
          <description>Patients diagnosed with juvenile-onset hypophosphatasia (HPP) [ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to &lt; 18 years of age].</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All patients who met all of the inclusion and none of the exclusion criteria were defined as the enrolled population, which was also the analysis population.</population>
      <group_list>
        <group group_id="B1">
          <title>Retrospective Observational</title>
          <description>Patients diagnosed with juvenile-onset hypophosphatasia (HPP) [ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to &lt; 18 years of age].</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <description>Age at Diagnosis</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.2" spread="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White, Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White, Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Modified Performance-Oriented Mobility Assessment - Gait subtest (MPOMA-G)</title>
          <description>The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.00" lower_limit="4.00" upper_limit="8.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Deceased/Alive Status - Deceased</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Deceased/Alive Status - Alive</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall</title>
        <description>The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
        <time_frame>The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Retrospective Observational</title>
            <description>Patients diagnosed with juvenile-onset hypophosphatasia (HPP) [ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to &lt; 18 years of age].</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall</title>
          <description>The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" lower_limit="1.00" upper_limit="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Videos were reviewed and scored by 3 independent raters who were masked to patient identifiers and the clinic visits and dates when the videos were recorded. Each rater scored the individual components required for the calculation of the total MPOMA-G score for each evaluable patient video. The median of the scores across the 3 raters was obtained for each individual component and summed to generate the median MPOMA-G score used in the analyses.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0625</p_value>
            <p_value_desc>The p-value is based on a nonparametric sign test to determine whether the median of change from Baseline in MPOMA-G score differs from 0. No multiple comparisons or multiplicity adjustments were conducted.</p_value_desc>
            <method>Sign test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall</title>
        <description>The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
        <time_frame>The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Retrospective Observational</title>
            <description>Patients diagnosed with juvenile-onset hypophosphatasia (HPP) [ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to &lt; 18 years of age].</description>
          </group>
        </group_list>
        <measure>
          <title>Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall</title>
          <description>The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" lower_limit="0.00" upper_limit="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Videos were reviewed and scored by 3 independent raters who were masked to patient identifiers and the clinic visits and dates when the videos were recorded. Each rater scored the individual components required for the calculation of the total POMA-G score for each evaluable patient video. The median of the scores across the 3 raters was obtained for each individual component and summed to generate the median POMA-G score used in the analyses.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1250</p_value>
            <p_value_desc>The p-value is based on a nonparametric sign test to determine whether the median of change from Baseline in POMA-G score differs from 0. No multiple comparisons or multiplicity adjustments were conducted.</p_value_desc>
            <method>Sign test</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>No adverse event data were collected during this retrospective noninterventional study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Retrospective Observational</title>
          <description>Patients diagnosed with juvenile-onset hypophosphatasia (HPP) [ie, documented onset of first signs/symptoms of HPP at ≥ 6 months to &lt; 18 years of age].</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Participation in this single-center study involves a commitment to publish the data from the study in a cooperative publication prior to release of study results on an individual basis. Therefore, the PI is subject to certain disclosure and publication limitations.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Medical Director, Clinical Development</name_or_title>
      <organization>Alexion Pharmaceuticals</organization>
      <phone>203-272-2596</phone>
      <email>clinicaltrials@alxn.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02235493
org study id: ALX-HPP-502s
nct id: NCT02235493
lead sponsor: 
has dmc: No
The purpose of this study is to characterize the natural history of HPP in patients with
      Juvenile-onset HPP who served as historical controls in ENB-006-09.
Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease
      characterized by defective bone mineralization and impaired phosphate and calcium regulation
      that can lead to progressive damage to multiple vital organs, including destruction and
      deformity of bones, profound muscle weakness, seizures, impaired renal function, and
      respiratory failure. There are no approved disease-modifying treatments for patients with
      this disease. There is also limited data available on the natural course of this disease over
      time, particularly in patients with the juvenile-onset form.
observational model: Other
time perspective: Retrospective
measure: Modified Performance-Oriented Mobility Assessment-Gait Subtest (MPOMA-G) - Change From Baseline to Last Overall
time frame: The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.
description: The MPOMA-G is a 5-component assessment that is used to evaluate gait performance. The first component has 4 sub-components. For 2 components and 2 sub-components, scores of 0 or 1 are assigned while scores of 0, 1 or 2 are assigned to the rest of the 2 components and 2 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.
measure: Performance-Oriented Mobility Assessment-Gait Subtest (POMA-G) - Change From Baseline to Last Overall
time frame: The earliest available MPOMA-G score that was assessed within the period of patients' aged 5 to 15 years, inclusive.
description: The POMA-G is a 7-component assessment that is used to evaluate gait performance. The second component has 4 sub-components. Scores of 0, 1 or 2 are assigned to 2 components while scores of 0 or 1 are assigned to the rest of the 4 components and 4 sub-components based on type of ambulation pattern observed. The maximum total score of 12 points = no impairment and 0 points = worst impairment.
arm group label: Retrospective Case Only
intervention type: Biological
intervention name: Retrospective Case Only
arm group label: Retrospective Case Only
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 5 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
url: http://www.hypophosphatasia.com
description: Hypophosphatasia Website
url: http://www.hypophosphatasia.com/hcp/
description: Hypophosphatasia Website for Health Care Professionals
url: http://www.magicfoundation.org
description: HPP support group
url: http://www.softbones.org
description: US Hypophosphatasia Group (Soft Bones)
responsible party type: Sponsor
mesh term: Bone Diseases
mesh term: Hypophosphatasia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 