<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/NCT01697319</url>
  </required_header>
  <id_info>
    <org_study_id>MOR-006</org_study_id>
    <secondary_id>2011-005703-33</secondary_id>
    <nct_id>NCT01697319</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation</brief_title>
  <official_title>A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioMarin Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioMarin Pharmaceutical</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a&#xD;
      patient population that has limited ambulation, in a period of up to 144 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Effect is defined by the following key domains:&#xD;
&#xD;
        -  Upper extremity function and dexterity&#xD;
&#xD;
        -  Mobility&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>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>Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)</measure>
    <time_frame>Up to 96 weeks</time_frame>
    <description>Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Mucopolysaccharidosis IVA</condition>
  <condition>Morquio A Syndrome</condition>
  <condition>MPS IVA</condition>
  <arm_group>
    <arm_group_label>BMN 110 at 2.0 mg/kg/week</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMN 110</intervention_name>
    <description>Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.</description>
    <arm_group_label>BMN 110 at 2.0 mg/kg/week</arm_group_label>
    <other_name>N-acetylgalactosamine-6-sulfatase</other_name>
    <other_name>N-acetylgalactosamine-6-sulfate</other_name>
    <other_name>sulfatase</other_name>
    <other_name>galactose-6-sulfatase</other_name>
    <other_name>GALNS</other_name>
    <other_name>enzyme replacement therapy</other_name>
    <other_name>ERT</other_name>
    <other_name>elosulfase alfa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is willing and able to provide written, signed informed consent (or their legally&#xD;
             authorized representative) after the nature of the study has been explained and prior&#xD;
             to performance of any research-related procedure. Patients who do not meet country and&#xD;
             local age requirements for informed consent must be willing and able to provide&#xD;
             written assent after the nature of the study has been explained and prior to&#xD;
             performance of any research-related procedure.&#xD;
&#xD;
          -  Has documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of&#xD;
             MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or&#xD;
             genetic testing confirming diagnosis of MPS IVA.&#xD;
&#xD;
          -  Is ≥ 5 years of age.&#xD;
&#xD;
          -  If sexually active, is willing to use an acceptable method of contraception while&#xD;
             participating in the study.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative pregnancy test at the Screening&#xD;
             Visit and be willing to have additional pregnancy tests during the study.&#xD;
&#xD;
          -  Is willing and able to perform all study procedures as physically possible.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is able to walk farther than a specified distance as assessed by the 6MWT.&#xD;
&#xD;
          -  Has previous hematopoietic stem cell transplant (HSCT).&#xD;
&#xD;
          -  Has received previous treatment with BMN 110.&#xD;
&#xD;
          -  Has a known hypersensitivity to any of the components of BMN 110.&#xD;
&#xD;
          -  Has had major surgery within 3 months prior to study entry or is planning to have a&#xD;
             major surgery during the first 24 weeks of the study.&#xD;
&#xD;
          -  Has used any other investigational product or investigational medical device within 30&#xD;
             days prior to the Screening Visit or requires any investigational agent prior to&#xD;
             completion of all scheduled study assessments.&#xD;
&#xD;
          -  Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant&#xD;
             (self or partner) at any time during the study.&#xD;
&#xD;
          -  Has a concurrent disease or condition, including but not limited to symptomatic&#xD;
             cervical spine instability or severe cardiac disease or complete paralysis due to a&#xD;
             spinal cord injury (defined as an inability to move arms and legs), that would&#xD;
             interfere with study participation or safety as determined by the Investigator.&#xD;
&#xD;
          -  Has any condition that, in the view of the Investigator, places the patient at high&#xD;
             risk of poor treatment compliance or of not completing the 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>
  <overall_official>
    <last_name>Celeste Decker, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>BioMarin Pharmaceutical</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital &amp; Research Center Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Manchester University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Royal NHS Foundation Trust</name>
      <address>
        <city>Salford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <results_first_submitted>October 12, 2015</results_first_submitted>
  <results_first_submitted_qc>December 8, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 12, 2016</results_first_posted>
  <last_update_submitted>December 8, 2015</last_update_submitted>
  <last_update_submitted_qc>December 8, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mucopolysaccharidosis IVA Type A</keyword>
  <keyword>MPS IVA Type A</keyword>
  <keyword>Mucopolysaccharidosis IVA</keyword>
  <keyword>MPS IVA</keyword>
  <keyword>Morquio A Syndrome</keyword>
  <keyword>Lysosomal Storage Disorder</keyword>
  <keyword>LSD</keyword>
  <keyword>N-acetylgalactosamine-6-sulfatase</keyword>
  <keyword>N-acetylgalactosamine-6-sulfate</keyword>
  <keyword>sulfatase</keyword>
  <keyword>galactose-6-sulfatase</keyword>
  <keyword>GALNS</keyword>
  <keyword>enzyme replacement therapy</keyword>
  <keyword>ERT</keyword>
  <keyword>MOR-006</keyword>
  <keyword>CPET</keyword>
  <keyword>Limited ambulation</keyword>
  <keyword>Grip/ Pinch</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucopolysaccharidoses</mesh_term>
    <mesh_term>Mucopolysaccharidosis IV</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>BMN 110 at 2.0 mg/kg/Week</title>
          <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Primary Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16">One subject enrolled but did not receive a single dose of study drug</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Extension Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BMN 110 at 2.0 mg/kg/Week</title>
          <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.7" spread="8.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>5 to 11 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 to 18 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=19 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)</title>
        <description>FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).</description>
        <time_frame>Up to 96 weeks</time_frame>
        <population>Modified ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>BMN 110 at 2.0 mg/kg/Week</title>
            <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)</title>
          <description>FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).</description>
          <population>Modified ITT Population</population>
          <units>% of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dominant Hand Wk 24 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="45.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dominant Hand Wk 48 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1" spread="53.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dominant Hand Wk 72 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.2" spread="54.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dominant Hand Wk 96 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5" spread="42.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Dominant Hand Wk 24 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.8" spread="32.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Dominant Hand Wk 48 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="35.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Dominant Hand Wk 72 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.3" spread="126.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Dominant Hand Wk 96 % Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)</title>
        <description>Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.</description>
        <time_frame>Up to 96 weeks</time_frame>
        <population>Modified ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>BMN 110 at 2.0 mg/kg/Week</title>
            <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)</title>
          <description>Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.</description>
          <population>Modified ITT Population</population>
          <units>% of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24 % Change from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-47.7" spread="15.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48 % Change from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.4" spread="24.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 72 % Change from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-45.5" spread="19.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 96 % Change from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-48.3" spread="24.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)</title>
        <description>A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.</description>
        <time_frame>Up to 96 weeks</time_frame>
        <population>Modified ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>BMN 110 at 2.0 mg/kg/Week</title>
            <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)</title>
          <description>A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.</description>
          <population>Modified ITT Population</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grip Dominant Hand Wk 24 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Dominant Hand Wk 48 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Dominant Hand Wk 72 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Dominant Hand Wk 96 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Non-Dominant Hand Wk24 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0" spread="0.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Non-Dominant Hand Wk 48 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Non-Dominant Hand Wk 72 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grip Non-Dominant Hand Wk 96 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Dominant Hand Wk 24 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Dominant Hand Wk 48 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0" spread="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Dominant Hand Wk 72 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Dominant Hand Wk 96 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="NA">One observation only</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Non-Dominant Hand Wk 24 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Non-Dominant Hand Wk 48 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" spread="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Non-Dominant Hand Wk 72 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pinch Non-Dominant Hand Wk 96 Chg from Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)</title>
        <description>The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.</description>
        <time_frame>Up to 96 weeks</time_frame>
        <population>Modified ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>BMN 110 at 2.0 mg/kg/Week</title>
            <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)</title>
          <description>The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.</description>
          <population>Modified ITT Population</population>
          <units>% of change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Wk 24 % Change from Baseline Two Attempts Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.7" spread="142.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Wk 48 % Change from Baseline Two Attempts Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.5" spread="102.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Wk 72 % Change from Baseline Two Attempts Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.3" spread="145.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Wk 96 % Change from Baseline Two Attempts Combined</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Small sample size and zero denominators</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Study Period</time_frame>
      <desc>All Adverse Events</desc>
      <group_list>
        <group group_id="E1">
          <title>BMN 110 at 2.0 mg/kg/Week</title>
          <description>Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pneumonia mycoplasmal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bone disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical cord compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Central venous catheterisation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular block first degree</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear discomfort</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Ear disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Otorrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal opacity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eye disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eyelid cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eyelid pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="12" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="28" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="19" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="29" subjects_affected="6" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Device occlusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Extravasation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Infusion site reaction</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Medical device pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nodule</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="26" subjects_affected="9" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergy to arthropod bite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Anaphylactoid reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Reaction to colouring</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="19" subjects_affected="9" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Otitis externa fungal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pulpitis dental</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin candida</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Subcutaneous abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="14" subjects_affected="7" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Chillblains</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Heat exhaustion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Tooth fracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Electrocardiogram PR prolongation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>QRS axis abnormal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="28" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="16" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pubic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sensation of heaviness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Tenosynovitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Burning sensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Clonus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="42" subjects_affected="11" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Dysmenorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="15" subjects_affected="6" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nasal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="14" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Restrictive pulmonary disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pigmentation disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash follicular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Skin disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Tooth extraction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>BioMarin Medical Information Services</name_or_title>
      <organization>BioMarin Pharmaceutical Inc.</organization>
      <phone>800-983-4587</phone>
      <email>medinfo@bmrn.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/NCT01697319
org study id: MOR-006
secondary id: 2011-005703-33
nct id: NCT01697319
lead sponsor: 
has dmc: Yes
The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a
      patient population that has limited ambulation, in a period of up to 144 weeks.
Effect is defined by the following key domains:

        -  Upper extremity function and dexterity

        -  Mobility
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)
time frame: Up to 96 weeks
description: FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
measure: Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)
time frame: Up to 96 weeks
description: A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
measure: Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)
time frame: Up to 96 weeks
description: The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.
measure: Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
time frame: Up to 96 weeks
description: Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.
arm group label: BMN 110 at 2.0 mg/kg/week
arm group type: Experimental
description: Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.
intervention type: Drug
intervention name: BMN 110
description: Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.
arm group label: BMN 110 at 2.0 mg/kg/week
other name: N-acetylgalactosamine-6-sulfatase
other name: N-acetylgalactosamine-6-sulfate
other name: sulfatase
other name: galactose-6-sulfatase
other name: GALNS
other name: enzyme replacement therapy
other name: ERT
other name: elosulfase alfa
criteria: 
gender: All
minimum age: 5 Years
maximum age: N/A
healthy volunteers: No
last name: Celeste Decker, M.D.
role: Study Director
affiliation: BioMarin Pharmaceutical
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Mucopolysaccharidoses
mesh term: Mucopolysaccharidosis IV
mesh term: Syndrome
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 