<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/NCT01685216</url>
  </required_header>
  <id_info>
    <org_study_id>HGT-GCB-068</org_study_id>
    <secondary_id>2012-003427-38</secondary_id>
    <nct_id>NCT01685216</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease</brief_title>
  <official_title>A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme&#xD;
      glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based&#xD;
      on the presence or absence of neurological symptoms and the severity of these neurological&#xD;
      symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration,&#xD;
      and those with type 3 disease typically display a more sub acute neurological course. Type 1&#xD;
      Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease&#xD;
      cases, does not involve the central nervous system.&#xD;
&#xD;
      The purpose of this clinical research study is to investigate the safety and effectiveness of&#xD;
      velaglucerase alfa in patients with type 3 Gaucher disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme&#xD;
      glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside&#xD;
      accumulates within the macrophages leading to cellular engorgement, organomegaly, and organ&#xD;
      system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the&#xD;
      presence or absence of neurological symptoms and severity of neurological symptoms. Patients&#xD;
      with type 2 Gaucher disease present with acute neurological deterioration, and those with&#xD;
      type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher&#xD;
      disease, the most common form accounting for more than 90% of all cases, does not involve the&#xD;
      central nervous system.&#xD;
&#xD;
      Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult&#xD;
      patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve&#xD;
      hematological parameters and positively impact health-related quality of life; ERTs have not&#xD;
      been shown to cross the blood brain barrier and as a result have shown limited ability to&#xD;
      improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher&#xD;
      disease.&#xD;
&#xD;
      This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa&#xD;
      in patients with type 3 Gaucher disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 14, 2012</start_date>
  <completion_date type="Actual">March 15, 2015</completion_date>
  <primary_completion_date type="Actual">March 15, 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration</measure>
    <time_frame>Baseline, Week 53 or end of study</time_frame>
    <description>Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to 12 Months (Week 53) in Platelet Count</measure>
    <time_frame>Baseline, Week 53</time_frame>
    <description>Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>Baseline, Week 51 or end of study</time_frame>
    <description>Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>Baseline, Week 51</time_frame>
    <description>Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Neurological Status During The Study</measure>
    <time_frame>Baseline, Weeks 13, 25, 37, and 53 or end of study</time_frame>
    <description>Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced a Treatment-Emergent Adverse Event</measure>
    <time_frame>57 weeks</time_frame>
    <description>Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study</measure>
    <time_frame>Baseline, Weeks 13, 25, 37 and 53</time_frame>
    <description>Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Gaucher Disease, Type 3</condition>
  <arm_group>
    <arm_group_label>velaglucerase alfa</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV infusion, 60 U/kg, every other week for 1 year</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>velaglucerase alfa</intervention_name>
    <description>lyophilized powder, intravenous infusion, units, Every other week (EOW)</description>
    <arm_group_label>velaglucerase alfa</arm_group_label>
    <other_name>VPRIV</other_name>
    <other_name>Gene activated glucocerebrosidase</other_name>
    <other_name>GA-GCB</other_name>
    <other_name>Enzyme replacement therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Each patient must meet the following criteria to be enrolled in this&#xD;
        study.&#xD;
&#xD;
          1. The patient has a confirmed diagnosis of type 3 Gaucher disease.&#xD;
&#xD;
          2. The patient is ≥ 2 and &lt; 18 years of age at the time of enrollment.&#xD;
&#xD;
          3. The patient is either näive to treatment or has not received treatment&#xD;
             (investigational or approved) for Gaucher disease within 12 months prior to study&#xD;
             entry.&#xD;
&#xD;
          4. The patient has Gaucher disease-related anemia, defined as hemoglobin concentration&#xD;
             below the lower limit of normal for age and sex.&#xD;
&#xD;
             AND ONE OR MORE OF THE FOLLOWING THREE CRITERIA&#xD;
&#xD;
               -  The patient has at least moderate splenomegaly (2 to 3 cm below the left costal&#xD;
                  margin) by palpation.&#xD;
&#xD;
               -  The patient has Gaucher disease-related thrombocytopenia, defined as platelet&#xD;
                  count &lt; 120 x 10,000 platelets/cubic mm.&#xD;
&#xD;
               -  The patient has a Gaucher disease-related readily palpable enlarged liver.&#xD;
&#xD;
          5. Patients who have undergone splenectomy may still be eligible to participate in the&#xD;
             study.&#xD;
&#xD;
          6. Female patients of child-bearing potential must agree to use a medically acceptable&#xD;
             method of contraception at all times during the study. Pregnancy testing will be&#xD;
             performed at the time of enrollment and as required throughout participation in the&#xD;
             study. Male patients must agree to use a medically acceptable method of contraception&#xD;
             at all times during the study and report a partner's pregnancy to the Investigator.&#xD;
&#xD;
          7. The patient's parent(s) or the patient's legally authorized representative(s) has&#xD;
             provided written informed consent that has been approved by the Institutional Review&#xD;
             Board/Independent Ethics Committee (IRB/IEC).&#xD;
&#xD;
        Exclusion Criteria: Patients who meet any of the following criteria will be excluded from&#xD;
        this study.&#xD;
&#xD;
          1. The patient is suspected of having type 2 or type 1 Gaucher disease.&#xD;
&#xD;
          2. The patient is &lt; 2 years of age.&#xD;
&#xD;
          3. The patient has experienced a severe (Grade 3 or higher) infusion-related&#xD;
             hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any enzyme&#xD;
             replacement therapy for Gaucher disease (approved or investigational).&#xD;
&#xD;
          4. The patient has received any non-Gaucher disease-related treatment with an&#xD;
             investigational drug within 30 days prior to study entry.&#xD;
&#xD;
          5. The patient is a pregnant and/or lactating female.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alexandria University Hospital</name>
      <address>
        <city>Alexandria</city>
        <zip>21131</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abu El Rich Hospital, Cairo University Hospital</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital, Ain Shams University Hospital</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KEM Hospital Research Centre</name>
      <address>
        <city>Pune</city>
        <state>Maharashtra</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Rabta</name>
      <address>
        <city>Tunis</city>
        <zip>1007</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
    <country>India</country>
    <country>Tunisia</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>September 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <results_first_submitted>October 1, 2015</results_first_submitted>
  <results_first_submitted_qc>October 1, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 30, 2015</results_first_posted>
  <last_update_submitted>May 18, 2021</last_update_submitted>
  <last_update_submitted_qc>May 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VPRIV</keyword>
  <keyword>velaglucerase alfa</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gaucher Disease</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Velaglucerase Alfa</title>
          <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </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="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Did not receive study drug</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
      <group_list>
        <group group_id="B1">
          <title>Velaglucerase Alfa</title>
          <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</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</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.17" spread="4.446"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>2 to 4 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 to 17 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration</title>
        <description>Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.</description>
        <time_frame>Baseline, Week 53 or end of study</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration</title>
          <description>Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</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="2.15" spread="1.213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to 12 Months (Week 53) in Platelet Count</title>
        <description>Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased.</description>
        <time_frame>Baseline, Week 53</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to 12 Months (Week 53) in Platelet Count</title>
          <description>Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased.</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>platelets (x10^9)/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</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="136.6" spread="51.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)</title>
        <description>Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased.</description>
        <time_frame>Baseline, Week 51 or end of study</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)</title>
          <description>Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased.</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>percent 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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-30.12" spread="10.366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)</title>
        <description>Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased.</description>
        <time_frame>Baseline, Week 51</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)</title>
          <description>Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased.</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>percent 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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-62.27" spread="19.991"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Neurological Status During The Study</title>
        <description>Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit.</description>
        <time_frame>Baseline, Weeks 13, 25, 37, and 53 or end of study</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Neurological Status During The Study</title>
          <description>Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit.</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>participants</units>
          <param>Number</param>
          <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="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced a Treatment-Emergent Adverse Event</title>
        <description>Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication.</description>
        <time_frame>57 weeks</time_frame>
        <population>The Safety Analysis population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced a Treatment-Emergent Adverse Event</title>
          <description>Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication.</description>
          <population>The Safety Analysis population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>participants</units>
          <param>Number</param>
          <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>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study</title>
        <description>Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer).</description>
        <time_frame>Baseline, Weeks 13, 25, 37 and 53</time_frame>
        <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
        <group_list>
          <group group_id="O1">
            <title>Velaglucerase Alfa</title>
            <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study</title>
          <description>Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer).</description>
          <population>The Intent-to-Treat population, defined as all participants who received at least 1 study drug infusion (full or partial).</population>
          <units>participants</units>
          <param>Number</param>
          <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>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 37</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 53</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Treatment-emergent adverse events are reported for the Safety population, defined as all participants who received at least 1 study drug infusion (full or partial).</desc>
      <group_list>
        <group group_id="E1">
          <title>Velaglucerase Alfa</title>
          <description>Participants received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (14.0)</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="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (14.0)</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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Strabismus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gingival bleeding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Acute tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Postprocedural cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Excoriation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chilblains</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </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="6" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Synovial cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fine motor delay</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gross motor delay</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Muscle spasticity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Heat rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </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>If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Shire</organization>
      <phone>+1 866 842 5335</phone>
      <email>ClinicalTransparency@shire.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/NCT01685216
org study id: HGT-GCB-068
secondary id: 2012-003427-38
nct id: NCT01685216
lead sponsor: 
has dmc: No
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme
      glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based
      on the presence or absence of neurological symptoms and the severity of these neurological
      symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration,
      and those with type 3 disease typically display a more sub acute neurological course. Type 1
      Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease
      cases, does not involve the central nervous system.

      The purpose of this clinical research study is to investigate the safety and effectiveness of
      velaglucerase alfa in patients with type 3 Gaucher disease.
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme
      glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside
      accumulates within the macrophages leading to cellular engorgement, organomegaly, and organ
      system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the
      presence or absence of neurological symptoms and severity of neurological symptoms. Patients
      with type 2 Gaucher disease present with acute neurological deterioration, and those with
      type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher
      disease, the most common form accounting for more than 90% of all cases, does not involve the
      central nervous system.

      Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult
      patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve
      hematological parameters and positively impact health-related quality of life; ERTs have not
      been shown to cross the blood brain barrier and as a result have shown limited ability to
      improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher
      disease.

      This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa
      in patients with type 3 Gaucher disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration
time frame: Baseline, Week 53 or end of study
description: Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.
measure: Change From Baseline to 12 Months (Week 53) in Platelet Count
time frame: Baseline, Week 53
description: Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased.
measure: Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)
time frame: Baseline, Week 51 or end of study
description: Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased.
measure: Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)
time frame: Baseline, Week 51
description: Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased.
measure: Number of Participants With Abnormal Neurological Status During The Study
time frame: Baseline, Weeks 13, 25, 37, and 53 or end of study
description: Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit.
measure: Number of Participants Who Experienced a Treatment-Emergent Adverse Event
time frame: 57 weeks
description: Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication.
measure: Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study
time frame: Baseline, Weeks 13, 25, 37 and 53
description: Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer).
arm group label: velaglucerase alfa
arm group type: Experimental
description: IV infusion, 60 U/kg, every other week for 1 year
intervention type: Biological
intervention name: velaglucerase alfa
description: lyophilized powder, intravenous infusion, units, Every other week (EOW)
arm group label: velaglucerase alfa
other name: VPRIV
other name: Gene activated glucocerebrosidase
other name: GA-GCB
other name: Enzyme replacement therapy
criteria: 
gender: All
minimum age: 2 Years
maximum age: 17 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
facility: 
facility: 
country: Egypt
country: India
country: Tunisia
responsible party type: Sponsor
mesh term: Gaucher Disease
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 