<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/NCT03004001</url>
  </required_header>
  <id_info>
    <org_study_id>VA16-029</org_study_id>
    <nct_id>NCT03004001</nct_id>
  </id_info>
  <brief_title>Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome</brief_title>
  <official_title>Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gloria Vega</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aventis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dallas VA Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study purpose is to determine the hypolipidemic effect of Alirocumab co-administered with&#xD;
      atorvastatin on levels of triglyceride-rich lipoproteins and LDL compared to monotherapy with&#xD;
      atorvastatin in patients with dyslipidemia secondary to nephrotic syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial is randomized (1:1 alirocumab to placebo), double-blinded, placebo-controlled with&#xD;
      a cross-over design. The trial will last 10 months and includes a 10 week washout period&#xD;
      between study phases.Twenty adult subjects with dyslipidemia secondary to nephrotic syndrome&#xD;
      and treated with atorvastatin will be recruited. Alirocumab or placebo will be&#xD;
      co-administered biweekly. Safety, efficacy chemistries, vital signs, anthropometry and&#xD;
      monitoring for adverse events also will done at each visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Difficult recruitment&#xD;
  </why_stopped>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Levels of plasma lipoproteins</measure>
    <time_frame>up to 10 months</time_frame>
    <description>ion mobility lipoprotein analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of PCSK9</measure>
    <time_frame>up to 10 months</time_frame>
    <description>immunoassay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglyceride-rich lipoproteins (Remnants)</measure>
    <time_frame>up to 10 months</time_frame>
    <description>immunoassay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipidomics</measure>
    <time_frame>up to 10 months</time_frame>
    <description>mass spectroscopy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Alirocumab and atorvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alirocumab placebo and atorvastatin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Alirocumab placebo biweekly and atorvastatin 20 mg/d</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alirocumab</intervention_name>
    <description>150 mg biweekly</description>
    <arm_group_label>Alirocumab and atorvastatin</arm_group_label>
    <other_name>Praluent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alirocumab placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Alirocumab placebo and atorvastatin</arm_group_label>
    <other_name>Praluent placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>20 mg/day</description>
    <arm_group_label>Alirocumab and atorvastatin</arm_group_label>
    <arm_group_label>Alirocumab placebo and atorvastatin</arm_group_label>
    <other_name>Lipitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Nephrotic Syndrome (NS) (FSGS, IMN or NS and type 2 DM)&#xD;
&#xD;
          -  atorvastatin&#xD;
&#xD;
          -  LDL C &gt;= 70 mg/dl or non-HDL C &gt;= 100 mg/dl&#xD;
&#xD;
          -  Plasma trigycerides &lt; 800 mg/dl.&#xD;
&#xD;
          -  Highly effective methods of contraception for pre-menopausal women&#xD;
&#xD;
          -  Post-menopausal women must be amenorrheic for at least 12 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  homozygous FH&#xD;
&#xD;
          -  Fibrates within 6 weeks of screening visit&#xD;
&#xD;
          -  Uncontrolled hypothyroidism&#xD;
&#xD;
          -  Known history of hemorrhagic stroke&#xD;
&#xD;
          -  Known history of loss of function of PCSK9&#xD;
&#xD;
          -  use of systemic corticosteroids unless used as replacement therapy for&#xD;
             pituitary/adrenal disease with a stable regimen for at least 6 weeks of randomization&#xD;
&#xD;
          -  Previous treatment with at least a single dose of alirocumab or any other anti-PCSK9&#xD;
             monoclonal antibody&#xD;
&#xD;
          -  Other conditions or situations per protocol&#xD;
&#xD;
          -  Laboratory findings or contraindications to background therapies&#xD;
&#xD;
          -  Warnings/precautions of use (when appropriate) as displayed in the respective national&#xD;
             product labeling&#xD;
&#xD;
          -  Any currently known contra-indication to study drug, pregnancy or breastfeeding of&#xD;
             infants.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gloria L Vega, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dallas VAMC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yin Oo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Dallas VA Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Michael Concepcion, MD</last_name>
    <role>Study Director</role>
    <affiliation>Dallas VA Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DallasVAMC</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. doi: 10.1038/ki.1988.125.</citation>
    <PMID>3165483</PMID>
  </reference>
  <reference>
    <citation>Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7. doi: 10.1159/000013549.</citation>
    <PMID>10644862</PMID>
  </reference>
  <reference>
    <citation>Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int. 1995 Feb;47(2):579-86. doi: 10.1038/ki.1995.73.</citation>
    <PMID>7723244</PMID>
  </reference>
  <reference>
    <citation>Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.</citation>
    <PMID>24315769</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>August 17, 2022</last_update_submitted>
  <last_update_submitted_qc>August 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Dallas VA Medical Center</investigator_affiliation>
    <investigator_full_name>Gloria Vega</investigator_full_name>
    <investigator_title>Principal Investigator at Dallas VA Medical Center</investigator_title>
  </responsible_party>
  <keyword>Severe proteinuria</keyword>
  <keyword>Dyslipidemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Alirocumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03004001
org study id: VA16-029
nct id: NCT03004001
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The study purpose is to determine the hypolipidemic effect of Alirocumab co-administered with
      atorvastatin on levels of triglyceride-rich lipoproteins and LDL compared to monotherapy with
      atorvastatin in patients with dyslipidemia secondary to nephrotic syndrome.
The trial is randomized (1:1 alirocumab to placebo), double-blinded, placebo-controlled with
      a cross-over design. The trial will last 10 months and includes a 10 week washout period
      between study phases.Twenty adult subjects with dyslipidemia secondary to nephrotic syndrome
      and treated with atorvastatin will be recruited. Alirocumab or placebo will be
      co-administered biweekly. Safety, efficacy chemistries, vital signs, anthropometry and
      monitoring for adverse events also will done at each visit.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Levels of plasma lipoproteins
time frame: up to 10 months
description: ion mobility lipoprotein analysis
measure: Levels of PCSK9
time frame: up to 10 months
description: immunoassay
measure: Triglyceride-rich lipoproteins (Remnants)
time frame: up to 10 months
description: immunoassay
measure: Lipidomics
time frame: up to 10 months
description: mass spectroscopy
arm group label: Alirocumab and atorvastatin
arm group type: Experimental
description: Alirocumab 150 mg bi-weekly and atorvastatin 20 mg/d
arm group label: Alirocumab placebo and atorvastatin
arm group type: Placebo Comparator
description: Alirocumab placebo biweekly and atorvastatin 20 mg/d
intervention type: Drug
intervention name: Alirocumab
description: 150 mg biweekly
arm group label: Alirocumab and atorvastatin
other name: Praluent
intervention type: Drug
intervention name: Alirocumab placebo
description: placebo
arm group label: Alirocumab placebo and atorvastatin
other name: Praluent placebo
intervention type: Drug
intervention name: Atorvastatin
description: 20 mg/day
arm group label: Alirocumab and atorvastatin
arm group label: Alirocumab placebo and atorvastatin
other name: Lipitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Gloria L Vega, PhD
role: Principal Investigator
affiliation: Dallas VAMC
last name: Yin Oo, MD
role: Study Director
affiliation: Dallas VA Medical Center
last name: Michael Concepcion, MD
role: Study Director
affiliation: Dallas VA Medical Center
facility: 
country: United States
citation: Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. doi: 10.1038/ki.1988.125.
PMID: 3165483
citation: Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7. doi: 10.1159/000013549.
PMID: 10644862
citation: Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int. 1995 Feb;47(2):579-86. doi: 10.1038/ki.1995.73.
PMID: 7723244
citation: Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.
PMID: 24315769
responsible party type: Sponsor-Investigator
investigator affiliation: Dallas VA Medical Center
investigator full name: Gloria Vega
investigator title: Principal Investigator at Dallas VA Medical Center
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Dyslipidemias
mesh term: Syndrome
mesh term: Atorvastatin
mesh term: Alirocumab
mesh term: Antibodies, Monoclonal
sharing ipd: Undecided