<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/NCT01722526</url>
  </required_header>
  <id_info>
    <org_study_id>DFI13412</org_study_id>
    <secondary_id>2012-003542-32</secondary_id>
    <secondary_id>SPHINGO00812</secondary_id>
    <nct_id>NCT01722526</nct_id>
  </id_info>
  <brief_title>Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients</brief_title>
  <official_title>An Open-label, Multicenter, Ascending Dose Study of the Tolerability and Safety of Recombinant Human Acid Sphingomyelinase (rhASM) in Patients With Acid Sphingomyelinase Deficiency (ASMD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM&#xD;
      in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose&#xD;
      administration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>Phase 1</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>Summary of Adverse Events (AEs)</measure>
    <time_frame>at least 26 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss)</measure>
    <time_frame>up to 26 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot</measure>
    <time_frame>up to 26 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Human Acid Sphingomyelinase Deficiency</condition>
  <arm_group>
    <arm_group_label>Recombinant human acid sphingomyelinase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive rhASM of an initial dose of 0.1 mg/kg, followed by several dose escalations, as tolerated, up to 3.0 mg/kg. All doses are given 2 weeks apart.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant human acid sphingomyelinase</intervention_name>
    <description>Administered intravenously every 2 weeks for 26 weeks</description>
    <arm_group_label>Recombinant human acid sphingomyelinase</arm_group_label>
    <other_name>GZ402665</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with documented non-neuronopathic acid sphingomyelinase deficiency&#xD;
&#xD;
          -  The patient has a diffusing capacity of carbon monoxide (DLco) &gt;20% and ≤80% of the&#xD;
             predicted normal value.&#xD;
&#xD;
          -  The patient has a spleen volume ≥6 multiples of normal(MN). A partial splenectomy will&#xD;
             be permitted if performed ≥1 year prior to Screening/Baseline and residual spleen&#xD;
             volume is ≥6 MN.&#xD;
&#xD;
          -  The patient who is receiving lipid lowering therapy should be on a stable dose and&#xD;
             regimen of lipid-lowering therapy(ies) for at least 12 weeks prior to&#xD;
             Screening/Baseline, with the patient expected to remain on the same dose and regimen&#xD;
             throughout the 26-week treatment period.&#xD;
&#xD;
          -  The patient who is female and of childbearing potential must have a negative serum&#xD;
             pregnancy test for β-HCG.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The patient is female and pregnant or lactating.&#xD;
&#xD;
          -  The patient has a Body Mass Index(BMI)&gt;30.&#xD;
&#xD;
          -  The patient has received an investigational drug within 30 days prior to study&#xD;
             enrollment&#xD;
&#xD;
          -  The patient has a medical condition or any extenuating circumstance that may&#xD;
             significantly interfere with study compliance, including all prescribed evaluations&#xD;
             and follow-up activities.&#xD;
&#xD;
          -  The patient has had a major organ transplant&#xD;
&#xD;
          -  ALT or AST &gt;250 IU/L or total bilirubin &gt;1.5 mg/dL.&#xD;
&#xD;
          -  The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior&#xD;
             to and 3 days after each rhASM infusion for the duration of the study.&#xD;
&#xD;
          -  The patient requires medications that may decrease rhASM&#xD;
&#xD;
          -  The patient is unwilling or unable to avoid the use of medications or herbal&#xD;
             supplements that may cause or prolong bleeding, or have potential hepatotoxicity&#xD;
             within 10 days prior to and 3 days after liver biopsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Genzyme, a Sanofi Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Mary's Hospital</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>November 5, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>July 29, 2015</last_update_submitted>
  <last_update_submitted_qc>July 29, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 30, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human acid sphingomyelinase deficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niemann-Pick Disease, Type A</mesh_term>
    <mesh_term>Niemann-Pick Diseases</mesh_term>
    <mesh_term>Niemann-Pick Disease, Type C</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01722526
org study id: DFI13412
secondary id: 2012-003542-32
secondary id: SPHINGO00812
nct id: NCT01722526
lead sponsor: 
has dmc: Yes
To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM
      in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose
      administration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Summary of Adverse Events (AEs)
time frame: at least 26 weeks
measure: Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss)
time frame: up to 26 weeks
measure: Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot
time frame: up to 26 weeks
arm group label: Recombinant human acid sphingomyelinase
arm group type: Experimental
description: Participants will receive rhASM of an initial dose of 0.1 mg/kg, followed by several dose escalations, as tolerated, up to 3.0 mg/kg. All doses are given 2 weeks apart.
intervention type: Drug
intervention name: Recombinant human acid sphingomyelinase
description: Administered intravenously every 2 weeks for 26 weeks
arm group label: Recombinant human acid sphingomyelinase
other name: GZ402665
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Genzyme, a Sanofi Company
facility: 
facility: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Niemann-Pick Disease, Type A
mesh term: Niemann-Pick Diseases
mesh term: Niemann-Pick Disease, Type C