<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/NCT04498910</url>
  </required_header>
  <id_info>
    <org_study_id>17124</org_study_id>
    <secondary_id>J1H-MC-LAJB</secondary_id>
    <nct_id>NCT04498910</nct_id>
  </id_info>
  <brief_title>A Study of LY3451838 in Participants With Migraine</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY3451838 in Adults With Treatment-Resistant Migraine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eli Lilly and Company</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>
      The reason for this study is to see if the study drug LY3451838 is safe and effective in&#xD;
      participants who have migraine that have not responded to other preventive treatments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2020</start_date>
  <completion_date type="Actual">November 9, 2022</completion_date>
  <primary_completion_date type="Actual">November 9, 2022</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline in the Number of Monthly Migraine Headache Days</measure>
    <time_frame>Baseline, Month 1</time_frame>
    <description>Change from Baseline in the Number of Monthly Migraine Headache Days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the Number of Monthly Headache Days</measure>
    <time_frame>Baseline, Month 1</time_frame>
    <description>Change from Baseline in the Number of Monthly Headache Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with ≥50% Reduction from Baseline in Monthly Migraine Headache Days</measure>
    <time_frame>Month 1</time_frame>
    <description>Percentage of Participants with ≥50% Reduction from Baseline in Monthly Migraine Headache Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with One or More Serious Adverse Event(s) (SAEs)</measure>
    <time_frame>Baseline up to 5 Months</time_frame>
    <description>Number of Participants with One or More SAEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3451838</measure>
    <time_frame>Baseline through Month 1</time_frame>
    <description>PK: AUC of LY3451838</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK: Maximum Observed Drug Concentration (Cmax) of LY3451838</measure>
    <time_frame>Baseline through Month 1</time_frame>
    <description>PK: Cmax of LY3451838</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>LY3451838</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LY3451838 given intravenously (IV)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo given IV</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LY3451838</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>LY3451838</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered IV</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must have a diagnosis of migraine with a history of migraine headaches of at least 1&#xD;
             year prior, and migraine onset prior to age 50.&#xD;
&#xD;
          -  Have completed at least 80% of required daily diary entries during the start of the&#xD;
             study.&#xD;
&#xD;
          -  Have documentation of previous failure of 2 to 4 standard-of-care migraine preventive&#xD;
             medication categories in the past 10 years.&#xD;
&#xD;
          -  Women of child-bearing potential must test negative for pregnancy as indicated by a&#xD;
             negative serum pregnancy test and negative urine pregnancy test.&#xD;
&#xD;
          -  Women of child-bearing potential who are abstinent or in a same sex relationship must&#xD;
             agree to either remain abstinent or to avoid sexual relationships with males.&#xD;
&#xD;
          -  Women of child-bearing potential who are not abstinent, must agree to use one highly&#xD;
             effective method of contraception, or a combination of two effective methods of&#xD;
             contraception during the study, as well as 5 months following.&#xD;
&#xD;
          -  Women not of childbearing potential may participate and include those who are: A.&#xD;
             Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal&#xD;
             ligation) or congenital anomaly; or B. Post-menopausal - defined as either:&#xD;
&#xD;
               -  i. a woman at least 40 years of age with an intact uterus, not on hormone&#xD;
                  therapy, who has cessation of menses for at least 1 year without an alternative&#xD;
                  medical cause, and a follicle-stimulating hormone greater than (&gt;) 40&#xD;
                  multi-international units per milliliter (mIU/mL); or&#xD;
&#xD;
               -  ii. a woman 55 or older not on hormone therapy, who has had at least 12 months of&#xD;
                  spontaneous amenorrhea; or&#xD;
&#xD;
               -  iii. a woman at least 55 years of age with a diagnosis of menopause prior to&#xD;
                  starting hormone replacement therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Are currently enrolled in any other clinical study or any other type of medical&#xD;
             research judged not to be compatible with this study.&#xD;
&#xD;
          -  Have participated, within the last 30 days or 5-half-lives (whichever is longer), in a&#xD;
             clinical study involving any investigational product. If the half-life of the&#xD;
             investigational product is unknown, 6 months should have passed prior.&#xD;
&#xD;
          -  Known hypersensitivity or intolerance to monoclonal antibodies or other therapeutic&#xD;
             proteins, or to common antihistamines, epinephrine, methyl prednisone or other&#xD;
             systemic corticosteroids.&#xD;
&#xD;
          -  Are currently receiving medication or other treatment for prevention of migraine&#xD;
             headaches. Participants must have discontinued such medications or treatments at least&#xD;
             2 weeks prior. Botulinum toxin A or B that has been administered in the head or neck&#xD;
             area use must be discontinued at least 3 months prior. Nerve blocks or device use&#xD;
             (such as transcranial magnetic stimulation or electrical nerve stimulation) in the&#xD;
             head or neck area for migraine treatment must be discontinued at least 30 days prior.&#xD;
             Anti-calcitonin gene-related peptide (CGRP) antibodies must be discontinued at least 5&#xD;
             half-lives prior.&#xD;
&#xD;
          -  Have previously failed more than 4 migraine preventive medication categories in the&#xD;
             past 10 years due to inadequate efficacy (that is, maximum tolerated dose for at least&#xD;
             2 months) and/or safety / tolerability reasons.&#xD;
&#xD;
          -  History of cluster headache or migraine subtypes including hemiplegic (sporadic or&#xD;
             familial) migraine, ophthalmoplegic migraine, retinal migraine, typical aura without&#xD;
             headache, complications of migraine and migraine with brainstem aura (basilar-type&#xD;
             migraine).&#xD;
&#xD;
          -  In the 3 months prior, have other types of headache besides migraine, tension type&#xD;
             headache, or medication overuse headache (MOH). (In other words, participants can have&#xD;
             migraine, tension type headache, or MOH in the 3 months prior, but they cannot have&#xD;
             other types of headache in that time).&#xD;
&#xD;
          -  History of head or neck injury within last 6 months.&#xD;
&#xD;
          -  History of traumatic cervical or head injury associated with significant change in the&#xD;
             quality or frequency of headaches.&#xD;
&#xD;
          -  Have reading of electrocardiogram (ECG) showing abnormalities considered incompatible&#xD;
             with the study.&#xD;
&#xD;
          -  Any liver tests outside the normal range.&#xD;
&#xD;
          -  Evidence of significant active or unstable psychiatric disease.&#xD;
&#xD;
          -  Women who are pregnant or nursing.&#xD;
&#xD;
          -  Participants who have used opioids or barbiturate-containing analgesic &gt;4 days per&#xD;
             month for the treatment of pain in each of the past 3 months.&#xD;
&#xD;
          -  History of drug or alcohol abuse/dependence within 1 year.&#xD;
&#xD;
          -  Have a positive urine drug screen for illicit drugs.&#xD;
&#xD;
          -  Are unwilling or unable to comply with the use of data collection devices.&#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>Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)</last_name>
    <role>Study Director</role>
    <affiliation>Eli Lilly and Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>21st Century Neurology, a division of Xenoscience</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85004-0000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New England Institute for Clinical Research</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renstar Medical Research</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34470</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emerald Coast Center for Neurological Disorders</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612-4799</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>StudyMetrix Research</name>
      <address>
        <city>Saint Peters</city>
        <state>Missouri</state>
        <zip>63303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinvest Research LLC</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bio Behavioral Health</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Research of Hampton Roads Inc</name>
      <address>
        <city>Newport News</city>
        <state>Virginia</state>
        <zip>23606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trials.lilly.com/en-US/trial/283602</url>
    <description>A Study of LY3451838 in Participants With Migraine</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>January 13, 2023</last_update_submitted>
  <last_update_submitted_qc>January 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</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>Migraine Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.</ipd_time_frame>
    <ipd_access_criteria>A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.</ipd_access_criteria>
    <ipd_url>http://vivli.org/</ipd_url>
  </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/NCT04498910
org study id: 17124
secondary id: J1H-MC-LAJB
nct id: NCT04498910
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The reason for this study is to see if the study drug LY3451838 is safe and effective in
      participants who have migraine that have not responded to other preventive treatments.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from Baseline in the Number of Monthly Migraine Headache Days
time frame: Baseline, Month 1
description: Change from Baseline in the Number of Monthly Migraine Headache Days
measure: Change from Baseline in the Number of Monthly Headache Days
time frame: Baseline, Month 1
description: Change from Baseline in the Number of Monthly Headache Days
measure: Percentage of Participants with ≥50% Reduction from Baseline in Monthly Migraine Headache Days
time frame: Month 1
description: Percentage of Participants with ≥50% Reduction from Baseline in Monthly Migraine Headache Days
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs)
time frame: Baseline up to 5 Months
description: Number of Participants with One or More SAEs
measure: Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3451838
time frame: Baseline through Month 1
description: PK: AUC of LY3451838
measure: PK: Maximum Observed Drug Concentration (Cmax) of LY3451838
time frame: Baseline through Month 1
description: PK: Cmax of LY3451838
arm group label: LY3451838
arm group type: Experimental
description: LY3451838 given intravenously (IV)
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo given IV
intervention type: Drug
intervention name: LY3451838
description: Administered IV
arm group label: LY3451838
intervention type: Drug
intervention name: Placebo
description: Administered IV
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: Study Director
affiliation: Eli Lilly and Company
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://trials.lilly.com/en-US/trial/283602
description: A Study of LY3451838 in Participants With Migraine
responsible party type: Sponsor
mesh term: Migraine Disorders
sharing ipd: Yes
ipd description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
ipd access criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
ipd url: http://vivli.org/