<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/NCT03773172</url>
  </required_header>
  <id_info>
    <org_study_id>AAAS0459</org_study_id>
    <nct_id>NCT03773172</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism</brief_title>
  <official_title>Study to Evaluate the Effects of Two Doses Over 48 Hours of MEDI6012 on Apolipoprotein B100 Metabolism in Subjects With Stable Atherosclerotic Cardiovascular Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MedImmune LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2, single-center, placebo controlled, double-blind, randomized crossover&#xD;
      study to determine the effects of MEDI6012 on the metabolism of apolipoprotein B100 (apoB100)&#xD;
      lipoproteins in individuals with stable atherosclerotic cardiovascular disease (ASCVD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atherosclerosis, characterized by excess fat deposit in arteries, is a progressive and&#xD;
      life-threatening condition. Therefore, treatments that can remove fat deposits from the&#xD;
      arteries are being developed. These treatments may prevent subsequent heart attacks or other&#xD;
      cardiovascular events, addressing an unmet medical need. MEDI16012 is a new drug that targets&#xD;
      a substance produced by the body to assist participants in breaking down the bodies &quot;good&quot;&#xD;
      fat. The investigators are interested in understanding why MEDI6012 increases the good fat,&#xD;
      but also why it increases other types of &quot;bad&quot; fat such as low-density lipoprotein-C (LDL-C).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Early termination due to COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">January 31, 2019</start_date>
  <completion_date type="Actual">May 20, 2020</completion_date>
  <primary_completion_date type="Actual">May 20, 2020</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in FCR of LDL-apoB100 (pools/day)</measure>
    <time_frame>Up to 48 hours from first dose</time_frame>
    <description>Fractional Clearance Rate (FCR) of lipoprotein B.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PR of LDL apoB100 (mg/kg/day)</measure>
    <time_frame>Up to 48 hours from first dose</time_frame>
    <description>Production Rate (PR) of LDL apoB 100.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>ADA Measurement</measure>
    <time_frame>Up to 60 days post administration of first dose</time_frame>
    <description>To access the immunogenicity of MEDI6012, anti-drug antibodies (ADA) will be measured.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Placebo Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive placebo treatment to mimic active treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose of MEDI6012 at 48 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MEDI6012</intervention_name>
    <description>MEDI6012 is recombinant human lecithin-cholesterol acyltransferase (rhLCAT), an approximately 60 kilodalton, glycosylated, single-chain protein consisting of 416 amino acids produced via Chinese hamster ovary cell culture. It is being explored as an acute treatment to reduce the risk of recurrent cardiovascular events as an adjunct to the standard of care in patients with acute myocardial infarction (MI). MEDI6012 and ACP501 have the identical amino acid sequence and are therefore considered the same molecular entity.</description>
    <arm_group_label>Active treatment</arm_group_label>
    <other_name>Stable Isotopes</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo will mimic the active treatment.</description>
    <arm_group_label>Placebo Control Group</arm_group_label>
    <other_name>Placebo compound provided by funding agency</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult male and female subjects (non-childbearing potential for females) ages 35&#xD;
             through 80 years at the time of screening who are capable of providing informed&#xD;
             consent prior to screening and any protocol-related procedures.&#xD;
&#xD;
          2. Written informed consent and any locally required authorization (e.g., Health&#xD;
             Insurance Portability and Accountability Act (HIPAA) in the USA) obtained from the&#xD;
             subject prior to performing any protocol-related procedures, including screening&#xD;
             evaluations.&#xD;
&#xD;
          3. Ability to complete and meet all eligibility requirements for randomization within 28&#xD;
             days of informed consent (56 days if washing out from lipid altering agent other than&#xD;
             statins or ezetimibe).&#xD;
&#xD;
          4. A diagnosis of stable atherosclerotic cardiovascular disease (CVD) documented prior to&#xD;
             screening:&#xD;
&#xD;
               -  Coronary artery disease defined as a history of prior myocardial infarction,&#xD;
                  coronary revascularization, history of coronary atherosclerosis based on invasive&#xD;
                  or non-invasive imaging, and/or abnormal stress testing diagnostic of coronary&#xD;
                  artery disease.&#xD;
&#xD;
               -  Carotid artery disease (extracranial internal carotid artery (ICA) stenosis)&#xD;
                  defined as evidence of carotid atherosclerosis by carotid imaging, or history of&#xD;
                  percutaneous or surgical carotid revascularization&#xD;
&#xD;
               -  Peripheral artery disease defined as ankle-brachial index &lt; 0.90 and&#xD;
                  claudication, or prior peripheral revascularization for ischemia, or evidence of&#xD;
                  lower extremity (below the inguinal ligament) atherosclerosis on invasive or&#xD;
                  noninvasive imaging&#xD;
&#xD;
          5. Currently receiving statin as standard of care, at a stable dose for ≥ 8 weeks prior&#xD;
             to screening and intended to remain at a stable dose throughout the study duration.&#xD;
             Subjects may also be receiving ezetimibe, 10 mg/day for ≥ 8 weeks prior to screening.&#xD;
&#xD;
          6. Nonsterilized males who are sexually active with a female partner of childbearing&#xD;
             potential must use condom and spermicide from Day 1 through the end of their&#xD;
             participation in the study. Because male condom and spermicide is not a highly&#xD;
             effective contraception method it is strongly recommended that female partners of a&#xD;
             male study subjects also use a highly effective method of contraception throughout&#xD;
             this period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable cardiovascular conditions within 3 months prior to screening, including acute&#xD;
             coronary syndrome (ACS), stroke or transient ischemia attack, critical limb ischemia,&#xD;
             non-elective arterial revascularization, life-threatening arrhythmias, or heart&#xD;
             failure hospitalization.&#xD;
&#xD;
          2. Elective arterial revascularization (in any vascular territory) in the past 1 month.&#xD;
             Any planned arterial revascularization (coronary, peripheral or carotid).&#xD;
&#xD;
          3. New York Heart Association (NYHA) Class III or IV congestive heart failure or&#xD;
             treatment with advanced therapies (cardiac transplant, ventricular assist device,&#xD;
             cardiac resynchronization therapy,and/or chronic IV inotropic support), or severe&#xD;
             valvular heart disease.&#xD;
&#xD;
          4. Body mass index &lt; 18 or &gt; 45.&#xD;
&#xD;
          5. Lipid measurements with any of the following:&#xD;
&#xD;
               1. Triglycerides (TG) &gt; 400 mg/dL&#xD;
&#xD;
               2. LDL-C &gt; 120 mg/dL&#xD;
&#xD;
               3. High-density lipoprotein C (HDL-C) &gt; 70 mg/dL for males or &gt; 80 mg/dL for&#xD;
                  females.&#xD;
&#xD;
          6. Clinically significant vital sign abnormalities at screening or on Day -1:&#xD;
&#xD;
               1. Systolic blood pressure (BP) &lt; 90 or &gt;160 mm Hg&#xD;
&#xD;
               2. Diastolic BP &gt; 100 mm Hg&#xD;
&#xD;
          7. Females currently breastfeeding or of childbearing potential. Females of childbearing&#xD;
             potential are defined as those who are not surgically sterile (i.e., bilateral tubal&#xD;
             ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not&#xD;
             postmenopausal; defined as 12 months with no menses without an alternative medical&#xD;
             cause and a follicle-stimulating hormone level in the central laboratory's normal&#xD;
             range for post-menopausal phase is required at screening.&#xD;
&#xD;
          8. Use of lipid-lowering medications, with the exception of statins and ezetimibe, and&#xD;
             the following dietary supplements: ≥ 2 grams/day of fish oil (≥ 2 grams/day&#xD;
             docosahexaenoic acid (DHA) and EPA combined), ≥ 30 grams/day of flaxseed oil or ground&#xD;
             flaxseed, red yeast extract, &gt; 100 mg/day of niacin. At the investigator's discretion,&#xD;
             subjects may undergo a 6-week washout period of any exclusionary lipid-lowering agents&#xD;
             with the expectation that post-washout lipid levels will be rechecked and acceptable&#xD;
             per above criteria.&#xD;
&#xD;
          9. History of any of the following:&#xD;
&#xD;
               -  Documented familial hypercholesterolemia&#xD;
&#xD;
               -  Chronic kidney disease defined by estimated glomerular filtration rate &lt; 30&#xD;
                  mL/min/1.73 m2 by the modification of diet in renal disease equation, or end&#xD;
                  stage renal disease treated with kidney transplant or renal replacement therapy&#xD;
&#xD;
               -  History of clinically overt chronic liver disease or biochemical evidence of&#xD;
                  liver disease&#xD;
&#xD;
               -  Poorly controlled endocrine disorder including:&#xD;
&#xD;
                    -  Type 1 Diabetes excluded&#xD;
&#xD;
                    -  Type 2 Diabetes Mellitus with glycated hemoglobin (HbA1c) &gt; 8.0% as assessed&#xD;
                       at screening or&#xD;
&#xD;
               -  Uncontrolled thyroid disorder defined as thyroid stimulating hormone (TSH)&gt; upper&#xD;
                  limit of normal (ULN) and abnormal free T4; subjects with thyroid deficiency&#xD;
                  should have received a stable dose of thyroid hormone for &gt; 6 weeks prior to&#xD;
                  screening and have a normal TSH.&#xD;
&#xD;
               -  Current or previous use of systemic corticosteroids within 28 days prior to&#xD;
                  screening. Topical, intra-articular, intranasal, inhaled, and ophthalmic steroid&#xD;
                  therapies are allowed&#xD;
&#xD;
               -  History of severe infection or ongoing febrile illness within 30 days of&#xD;
                  screening, or a medical history of a chronic viral illness including hepatitis B&#xD;
                  or C virus, or human immunodeficiency virus (HIV).&#xD;
&#xD;
               -  History of active malignancy within 5 years (subjects with non-melanotic skin&#xD;
                  cancer may be included)&#xD;
&#xD;
               -  Any other disease or condition or laboratory value that, in the opinion of the&#xD;
                  investigator or medical monitor, would place the subject at an unacceptable risk&#xD;
                  or interfere with the evaluation of the investigative product.&#xD;
&#xD;
               -  Known allergy/hypersensitivity to any component of the investigational product&#xD;
                  formulation, other biologics, IV infusion equipment, plastics, adhesive or&#xD;
                  silicone, history of infusion site reactions with IV administration of other&#xD;
                  medicines, or ongoing clinically important allergy/hypersensitivity as judged by&#xD;
                  the investigator.&#xD;
&#xD;
         10. Subjects who are legally institutionalized&#xD;
&#xD;
         11. Previous Exposure to rhLCAT&#xD;
&#xD;
         12. Concurrent enrollment in another clinical study of any investigational drug therapy or&#xD;
             use of any biologicals within 6 months prior to screening or within 5 half-lives of an&#xD;
             investigational agent or biologic, whichever is longer.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henry Ginsberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>December 10, 2020</last_update_submitted>
  <last_update_submitted_qc>December 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lipid and Lipoprotein Metabolism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 24, 2021</submitted>
    <returned>June 16, 2021</returned>
    <submitted>January 12, 2022</submitted>
    <returned>February 7, 2022</returned>
  </pending_results>
  <!-- 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/NCT03773172
org study id: AAAS0459
nct id: NCT03773172
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2, single-center, placebo controlled, double-blind, randomized crossover
      study to determine the effects of MEDI6012 on the metabolism of apolipoprotein B100 (apoB100)
      lipoproteins in individuals with stable atherosclerotic cardiovascular disease (ASCVD).
Atherosclerosis, characterized by excess fat deposit in arteries, is a progressive and
      life-threatening condition. Therefore, treatments that can remove fat deposits from the
      arteries are being developed. These treatments may prevent subsequent heart attacks or other
      cardiovascular events, addressing an unmet medical need. MEDI16012 is a new drug that targets
      a substance produced by the body to assist participants in breaking down the bodies "good"
      fat. The investigators are interested in understanding why MEDI6012 increases the good fat,
      but also why it increases other types of "bad" fat such as low-density lipoprotein-C (LDL-C).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent Change in FCR of LDL-apoB100 (pools/day)
time frame: Up to 48 hours from first dose
description: Fractional Clearance Rate (FCR) of lipoprotein B.
measure: PR of LDL apoB100 (mg/kg/day)
time frame: Up to 48 hours from first dose
description: Production Rate (PR) of LDL apoB 100.
measure: ADA Measurement
time frame: Up to 60 days post administration of first dose
description: To access the immunogenicity of MEDI6012, anti-drug antibodies (ADA) will be measured.
arm group label: Placebo Control Group
arm group type: Placebo Comparator
description: Subjects will receive placebo treatment to mimic active treatment.
arm group label: Active treatment
arm group type: Active Comparator
description: IV push loading dose of 300 mg MEDI6012 followed by a 150 mg maintenance dose of MEDI6012 at 48 hours.
intervention type: Drug
intervention name: MEDI6012
description: MEDI6012 is recombinant human lecithin-cholesterol acyltransferase (rhLCAT), an approximately 60 kilodalton, glycosylated, single-chain protein consisting of 416 amino acids produced via Chinese hamster ovary cell culture. It is being explored as an acute treatment to reduce the risk of recurrent cardiovascular events as an adjunct to the standard of care in patients with acute myocardial infarction (MI). MEDI6012 and ACP501 have the identical amino acid sequence and are therefore considered the same molecular entity.
arm group label: Active treatment
other name: Stable Isotopes
intervention type: Drug
intervention name: Placebo
description: The placebo will mimic the active treatment.
arm group label: Placebo Control Group
other name: Placebo compound provided by funding agency
criteria: 
gender: All
minimum age: 35 Years
maximum age: 80 Years
healthy volunteers: No
last name: Henry Ginsberg, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
sharing ipd: No
submitted: May 24, 2021
returned: June 16, 2021
submitted: January 12, 2022
returned: February 7, 2022