<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/NCT03038022</url>
  </required_header>
  <id_info>
    <org_study_id>MGL-3196-06</org_study_id>
    <nct_id>NCT03038022</nct_id>
  </id_info>
  <brief_title>Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)</brief_title>
  <official_title>A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo Controlled Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Madrigal Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Madrigal Pharmaceuticals, Inc.</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on&#xD;
      the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients&#xD;
      with Heterozygous Familial Hypercholesterolemia (HeFH).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 9, 2017</start_date>
  <completion_date type="Actual">January 15, 2018</completion_date>
  <primary_completion_date type="Actual">December 18, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C)</measure>
    <time_frame>12 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values</measure>
    <time_frame>12 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean percent change from baseline on selected lipid parameters</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Non-high-density lipoprotein cholesterol (non-HDL-C),Apolipoprotein B (ApoB), Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, Triglycerides,Lipoprotein(a), Apolipoprotein A1 (ApoA1)/ApoB ratio, and Lipoprotein particle assessment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Heterozygous Familial Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>MGL-3196</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study Drug</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MGL-3196</intervention_name>
    <description>Oral</description>
    <arm_group_label>MGL-3196</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be willing to participate in the study and provide written informed consent;&#xD;
&#xD;
          -  Male and female adults ≥18 years of age;&#xD;
&#xD;
          -  Female patients of child bearing potential with negative serum pregnancy (beta human&#xD;
             chorionic gonadotropin) test who are not breastfeeding, do not plan to become pregnant&#xD;
             during the study, and agree to use effective birth control (ie, condoms, diaphragm,&#xD;
             non-hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line&#xD;
             with the patient's current lifestyle]) throughout the study and for at least 1 month&#xD;
             after study completion; hormonal contraception (estrogens stable ≥3 months) and&#xD;
             hormonal IUDs are permitted if used with a secondary birth control measure (eg,&#xD;
             condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral&#xD;
             oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [&gt;12 consecutive&#xD;
             months without menses]); male patients who have sexual intercourse with a female&#xD;
             partner of child bearing potential from the first dose of study drug until 1 month&#xD;
             after study completion must either be surgically sterile (confirmed by documented&#xD;
             azoospermia &gt;90 days after the procedure) OR agree to use a condom with spermicide.&#xD;
             All male patients must agree not to donate sperm from the first dose of study drug&#xD;
             until 1 month after study completion;&#xD;
&#xD;
          -  Must have a diagnosis of HeFH by genetic testing or by having met the diagnostic&#xD;
             criteria for definite familial hypercholesterolemia outlined by the Simon Broome&#xD;
             Register Group or WHO/Dutch Lipid Network (score &gt;8);&#xD;
&#xD;
          -  Must have a fasting LDL-C ≥ 2.6 mmol/L (100 mg/dL); and&#xD;
&#xD;
          -  Must be on a stable or maximally tolerated dose (≥ 4 weeks prior to screening) of an&#xD;
             approved statin (rosuvastatin ≤ 20 mg daily, atorvastatin ≤ 80 mg daily), with or&#xD;
             without ezetimibe.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Homozygous familial hypercholesterolemia&#xD;
&#xD;
          -  Low-density lipoprotein (LDL) or plasma apheresis within 2 months prior to&#xD;
             randomization;&#xD;
&#xD;
          -  New York Heart Association class III or IV heart failure, or known left ventricular&#xD;
             ejection fraction &lt;30%;&#xD;
&#xD;
          -  Uncontrolled cardiac arrhythmia, including confirmed QT interval corrected using&#xD;
             Fridericia's formula (QTcF) &gt;450 msec for males and &gt;470 msec for females at the&#xD;
             screening electrocardiogram (ECG) assessment;&#xD;
&#xD;
          -  Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary&#xD;
             artery bypass graft, or stroke within 3 months prior to randomization;&#xD;
&#xD;
          -  Type 1 diabetes, or newly diagnosed or uncontrolled type 2 diabetes (hemoglobin A1c&#xD;
             [HbA1c] &gt;8%);&#xD;
&#xD;
          -  History of significant alcohol consumption for a period of more than 3 consecutive&#xD;
             months within 1 year prior to screening; Note: Significant alcohol consumption is&#xD;
             defined as average of &gt;20 g/day in female patients and &gt;30 g/day in male patients;&#xD;
&#xD;
          -  Thyroid replacement therapy;&#xD;
&#xD;
          -  Evidence of chronic liver disease;&#xD;
&#xD;
          -  Hepatitis B, as defined by the presence of hepatitis B surface antigen;&#xD;
&#xD;
          -  Hepatitis C, as defined by the presence of hepatitis C virus (HCV) antibody (anti-HCV)&#xD;
             and HCV ribonucleic acid (RNA). Patients with positive anti-HCV who test negative for&#xD;
             HCV RNA at screening will be allowed to participate in the study;&#xD;
&#xD;
          -  Serum alanine aminotransferase (ALT) &gt;1.5 × ULN (one repeat allowed);&#xD;
&#xD;
          -  Estimated glomerular filtration rate &lt;60 mL/min;&#xD;
&#xD;
          -  Creatine kinase &gt;3 × ULN (one repeat allowed);&#xD;
&#xD;
          -  History of biliary diversion;&#xD;
&#xD;
          -  Positive for human immunodeficiency virus infection;&#xD;
&#xD;
          -  History of malignant hypertension;&#xD;
&#xD;
          -  Systolic blood pressure &gt;160 mmHg or diastolic blood pressure &gt;100 mmHg at screening&#xD;
             or randomization and confirmed at an unscheduled visit;&#xD;
&#xD;
          -  Triglycerides &gt;5.7 mmol/L (500 mg/dL) at screening and confirmed by repeat assessment;&#xD;
&#xD;
          -  Active, serious medical disease with likely life expectancy &lt;2 years;&#xD;
&#xD;
          -  Active substance abuse, including inhaled or injection drugs within the year prior to&#xD;
             screening;&#xD;
&#xD;
          -  Participation in an investigational new drug trial within the 30 days prior to&#xD;
             randomization; or&#xD;
&#xD;
          -  Any other condition which, in the opinion of the Investigator, would impede&#xD;
             compliance, hinder completion of the study, or compromise the well-being of the&#xD;
             patient.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca Taub, MD</last_name>
    <role>Study Director</role>
    <affiliation>Madrigal Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Madrigal Research Site</name>
      <address>
        <city>Aalborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Madrigal Research Site</name>
      <address>
        <city>Viborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>January 23, 2018</last_update_submitted>
  <last_update_submitted_qc>January 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03038022
org study id: MGL-3196-06
nct id: NCT03038022
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on
      the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients
      with Heterozygous Familial Hypercholesterolemia (HeFH).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
time frame: 12 Weeks
measure: Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values
time frame: 12 Weeks
measure: Mean percent change from baseline on selected lipid parameters
time frame: 12 Weeks
description: Non-high-density lipoprotein cholesterol (non-HDL-C),Apolipoprotein B (ApoB), Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, Triglycerides,Lipoprotein(a), Apolipoprotein A1 (ApoA1)/ApoB ratio, and Lipoprotein particle assessment
arm group label: MGL-3196
arm group type: Experimental
description: Study Drug
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching Placebo
intervention type: Drug
intervention name: MGL-3196
description: Oral
arm group label: MGL-3196
intervention type: Drug
intervention name: Placebo
description: Oral
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rebecca Taub, MD
role: Study Director
affiliation: Madrigal Pharmaceuticals, Inc.
facility: 
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Hyperlipoproteinemia Type II
mesh term: Hypercholesterolemia
sharing ipd: No