<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/NCT04461795</url>
  </required_header>
  <id_info>
    <org_study_id>19-001TE</org_study_id>
    <nct_id>NCT04461795</nct_id>
  </id_info>
  <brief_title>Efficacy of AJOVY (Fremanezumab-vfrm) on Interictal Migraine Related Burden</brief_title>
  <official_title>A Multicenter, Open Label Study Assessing the Efficacy of AJOVY (Fremanezumab-vfrm) on Interictal Migraine Related Burden</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>David True</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clinvest Research, LLC</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being conducted to evaluate the efficacy and safety of AJOVY&#xD;
      (fremanezumab-vfrm) on interictal migraine related burden in adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single group, multicenter, open-label study with a study population of patients who&#xD;
      meet International Classification of Headache Disorders 3rd edition (ICHD-III) criteria for&#xD;
      migraine with or without aura and have 4 to 22 migraine days per month. This is a&#xD;
      single-group supportive care study with one arm and no masking. A maximum of 40 participants&#xD;
      will be enrolled to study intervention. All participants in this single-group study will&#xD;
      complete a 4-week run-in period. After the run-in period, eligible participants will be&#xD;
      enrolled to study intervention and enter a 12-week treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Actual">January 10, 2022</completion_date>
  <primary_completion_date type="Actual">January 10, 2022</primary_completion_date>
  <phase>Phase 4</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>Comparison of the mean change from baseline in the frequency of migraine headache days per 28-day period ending with the cessation of treatment month 3. A migraine headache day will be defined as a calendar day (00:00 to 23:59) with 4 or more hours of migraine headache, fulfilling International Classification of Headache Disorders-3 criteria, and/or any headache of any duration with the use of migraine-specific acute medications(s) (i.e. ergot alkaloids, ergot combinations, opioids, triptans, combination analgesics [simple analgesics combined with opioids or barbiturate with or without caffeine]). Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The Neuro-QoL Sleep Disturbance Short Form (SDSF) is an 8-item, self-administered questionnaire which measures quality of sleep including difficulties and perception of sleep satisfaction. Possible scores range from 8 to 40, with higher scores indicating worse sleep habits. Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The General Self-Efficacy - Short Form (GSE-SF) is a 4 item, self-administered questionnaire where the participant is asked to rate their confidence in managing situations, problems, and events. Scores range from 4-20. Higher scores indicate the participant has more self-efficacy managing difficult situations. Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) has 7 domains each with 4 questions, and then one global Pain Intensity item. The domains include: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. The global item domain is Pain Intensity. Each PROMIS domain can range from a score of 4-20, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).&#xD;
The outcome measure for this endpoint is the change in the global item (Pain Intensity) from baseline. The Global Pain Intensity item can range from 0-10, with higher scores indicating more severe pain intensity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The Work Productivity and Activity Impairment - Migraine (WPAI-M) is a 6-item self-administered questionnaire that measures work productivity and the amount of time missed from work due to migraine. Scores are based on a percentage, so the range of scores is 0-100%, with higher scores indicating greater impairment and less productivity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12.</measure>
    <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
    <description>The Brief Measure of Worry Severity (BMWS) is a 8-item, self-administered questionnaire that measures various components of dysfunctional worry. Score range from 0-24 with higher scores indicating more worry within the participant. Change = (Applicable Treatment Month Score - Baseline Score)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>AJOVY (fremanezumab-vfrm)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]</intervention_name>
    <description>225 MG/1.5 ML Subcutaneous Solution</description>
    <arm_group_label>AJOVY (fremanezumab-vfrm)</arm_group_label>
    <other_name>fremanezumab-vfrm</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. willing to participate and sign informed consent;&#xD;
&#xD;
          2. ability to read and understand informed consent and study procedures, including able&#xD;
             to use the electronic Daily Headache Diary;&#xD;
&#xD;
          3. in good general health based on investigator's judgment;&#xD;
&#xD;
          4. must be between 18 to 65 years of age, inclusive, at time of Visit 2;&#xD;
&#xD;
          5. have migraine with and/or without aura meeting the diagnostic criteria listed in the&#xD;
             International Classification of Headache Disorders 3rd edition (ICHD-III; Appendix 5);&#xD;
&#xD;
          6. verification of headache frequency through prospectively collected baseline&#xD;
             information during the 28-day screening/baseline phase reporting 4-22 migraine days&#xD;
             and no more than 22 total headache days;&#xD;
&#xD;
          7. onset of migraine before age 50;&#xD;
&#xD;
          8. able to differentiate migraine from other primary headache types allowed in the study&#xD;
             (e.g., tension-type headache);&#xD;
&#xD;
          9. stable history of migraine at least 3 months prior to screening with at least some&#xD;
             discreet headache free periods;&#xD;
&#xD;
         10. not currently taking a migraine preventive OR has been taking a stable dose of a&#xD;
             preventive for at least 90 days prior to screening and agrees to not start, stop, or&#xD;
             change medication and/or dosage during the study period;&#xD;
&#xD;
             * * participants on migraine preventive should have stable headache pattern&#xD;
&#xD;
         11. women may be included only if they have a negative pregnancy test at screening and&#xD;
             baseline, are sterile, or postmenopausal. Women of childbearing potential (WOCBP)&#xD;
             engaging in potentially procreative intercourse must use highly effective birth&#xD;
             control methods for the duration of the study (i.e., starting at screening).&#xD;
             Definitions of WOCBP, sterile and postmenopausal women, male contraception, and highly&#xD;
             effective and acceptable birth control methods are to be determined based on&#xD;
             investigator's judgment;&#xD;
&#xD;
         12. demonstrated compliance with the electronic Daily Headache Diary during the 28-day&#xD;
             screening/baseline phase as defined by entry of headache data on a minimum of 23 days;&#xD;
&#xD;
         13. is willing to wear activity/sleep tracker throughout the duration of the trial;&#xD;
&#xD;
         14. has a smartphone and willing to install activity tracker app on phone.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. unable to understand the study requirements, the informed consent, or complete&#xD;
             headache records as required per protocol;&#xD;
&#xD;
          2. pregnant, actively trying to become pregnant, or breast-feeding;&#xD;
&#xD;
          3. history of substance abuse and/or dependence that would interfere study conduction, in&#xD;
             the opinion of the Investigator;&#xD;
&#xD;
          4. history of impaired renal function that, in the investigator's opinion,&#xD;
             contraindicates participation in this study;&#xD;
&#xD;
          5. suffers from a serious illness, or an unstable medical condition, one that could&#xD;
             require hospitalization, increase the risk of adverse events, or compromise data&#xD;
             integrity (ie, likely require changes in con meds or lead to other medical&#xD;
             investigations or treatments during the study).&#xD;
&#xD;
          6. a psychiatric condition, in the opinion of the investigator, that may affect the&#xD;
             interpretation of efficacy and safety data or contraindicates the participant's&#xD;
             participation in the study;&#xD;
&#xD;
          7. received nerve blocks or trigger point injections in the previous 8 weeks or plans to&#xD;
             receive them during the study;&#xD;
&#xD;
          8. prior exposure in the last 6 months, or 5 half-lives, to biologics or drugs&#xD;
             specifically targeting the calcitonin gene-related peptide (CGRP) pathway;&#xD;
&#xD;
          9. has failed more than 3 classes of medications for the prevention of migraine or &gt;6&#xD;
             migraine preventive medications of any type due to lack of efficacy;&#xD;
&#xD;
         10. received any investigational agents within 30 days prior to Visit 1 (6 months for any&#xD;
             investigational biological products unless previous study blind has been broken and&#xD;
             subject was known to have received placebo);&#xD;
&#xD;
         11. plans to participate in another clinical study at any time during this study;&#xD;
&#xD;
         12. history of medication overuse of opioids or butalbital, as defined by opioid or&#xD;
             butalbital use ≥10 days/month in each of the previous 3 months or during run-in&#xD;
             period; Medication Overuse Headache (MOH) with other medication types will be allowed&#xD;
             but must be documented;&#xD;
&#xD;
         13. unstable medication use for migraine prevention (changes in the last 3 months);&#xD;
&#xD;
         14. clinically relevant lab results at screening as determined by the investigator;&#xD;
&#xD;
         15. clinically relevant or significant ECG abnormalities as determined by the&#xD;
             investigator, including ECG with QT interval corrected for heart rate (QTc) using&#xD;
             Fridericia's correction formula (QTcF) &gt; 500 msec;&#xD;
&#xD;
         16. history of any of the following cardiovascular conditions:&#xD;
&#xD;
               1. Moderate to severe congestive heart failure (New York Heart Association class III&#xD;
                  or IV);&#xD;
&#xD;
               2. Recent (within past 6 months) cerebrovascular accident, myocardial infarction,&#xD;
                  coronary stenting;&#xD;
&#xD;
               3. Uncontrolled hypertension as defined by a confirmed systolic blood pressure &gt; 160&#xD;
                  mmHg or diastolic blood pressure &gt; 100 mmHg.&#xD;
&#xD;
         17. Subjects known to have active HIV or untreated Hepatitis C infection;&#xD;
&#xD;
         18. score of &gt; 0 on question 9 on Patient Health Questionnaire (PHQ-9) at any visit;&#xD;
&#xD;
         19. have any other condition, that in the judgment of the investigator, would make the&#xD;
             participant unsuitable for inclusion, or would interfere with the participant&#xD;
             participating in or completing the study.&#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>David True</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinvest Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>StudyMetrix</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <results_first_submitted>March 14, 2022</results_first_submitted>
  <results_first_submitted_qc>April 12, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <last_update_submitted>April 12, 2022</last_update_submitted>
  <last_update_submitted_qc>April 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Clinvest Research, LLC</investigator_affiliation>
    <investigator_full_name>David True</investigator_full_name>
    <investigator_title>Medical Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erenumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 5, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT04461795/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>AJOVY (Fremanezumab-vfrm)</title>
          <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Specified Withdrawal Criterion Met</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AJOVY (Fremanezumab-vfrm)</title>
          <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.38" spread="11.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.05" spread="2.04"/>
                    <measurement group_id="O2" value="-0.37" spread="1.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.71" spread="2.59"/>
                    <measurement group_id="O2" value="-0.63" spread="2.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.71" spread="2.10"/>
                    <measurement group_id="O2" value="-1.16" spread="2.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12.</title>
        <description>Comparison of the mean change from baseline in the frequency of migraine headache days per 28-day period ending with the cessation of treatment month 3. A migraine headache day will be defined as a calendar day (00:00 to 23:59) with 4 or more hours of migraine headache, fulfilling International Classification of Headache Disorders-3 criteria, and/or any headache of any duration with the use of migraine-specific acute medications(s) (i.e. ergot alkaloids, ergot combinations, opioids, triptans, combination analgesics [simple analgesics combined with opioids or barbiturate with or without caffeine]). Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12.</title>
          <description>Comparison of the mean change from baseline in the frequency of migraine headache days per 28-day period ending with the cessation of treatment month 3. A migraine headache day will be defined as a calendar day (00:00 to 23:59) with 4 or more hours of migraine headache, fulfilling International Classification of Headache Disorders-3 criteria, and/or any headache of any duration with the use of migraine-specific acute medications(s) (i.e. ergot alkaloids, ergot combinations, opioids, triptans, combination analgesics [simple analgesics combined with opioids or barbiturate with or without caffeine]). Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>migraine days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.05" spread="3.41"/>
                    <measurement group_id="O2" value="-0.9" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.71" spread="3.09"/>
                    <measurement group_id="O2" value="-2.42" spread="3.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.00" spread="3.30"/>
                    <measurement group_id="O2" value="-3.53" spread="3.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The Neuro-QoL Sleep Disturbance Short Form (SDSF) is an 8-item, self-administered questionnaire which measures quality of sleep including difficulties and perception of sleep satisfaction. Possible scores range from 8 to 40, with higher scores indicating worse sleep habits. Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The Neuro-QoL Sleep Disturbance Short Form (SDSF) is an 8-item, self-administered questionnaire which measures quality of sleep including difficulties and perception of sleep satisfaction. Possible scores range from 8 to 40, with higher scores indicating worse sleep habits. Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.85" spread="5.20"/>
                    <measurement group_id="O2" value="-4.33" spread="6.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.30" spread="5.49"/>
                    <measurement group_id="O2" value="-3.5" spread="6.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.66" spread="5.75"/>
                    <measurement group_id="O2" value="-5.23" spread="6.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The General Self-Efficacy - Short Form (GSE-SF) is a 4 item, self-administered questionnaire where the participant is asked to rate their confidence in managing situations, problems, and events. Scores range from 4-20. Higher scores indicate the participant has more self-efficacy managing difficult situations. Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The General Self-Efficacy - Short Form (GSE-SF) is a 4 item, self-administered questionnaire where the participant is asked to rate their confidence in managing situations, problems, and events. Scores range from 4-20. Higher scores indicate the participant has more self-efficacy managing difficult situations. Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.12" spread="7.02"/>
                    <measurement group_id="O2" value="2.04" spread="7.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="9.13"/>
                    <measurement group_id="O2" value="1.55" spread="9.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.04" spread="7.44"/>
                    <measurement group_id="O2" value="0.98" spread="9.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) has 7 domains each with 4 questions, and then one global Pain Intensity item. The domains include: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. The global item domain is Pain Intensity. Each PROMIS domain can range from a score of 4-20, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).&#xD;
The outcome measure for this endpoint is the change in the global item (Pain Intensity) from baseline. The Global Pain Intensity item can range from 0-10, with higher scores indicating more severe pain intensity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) has 7 domains each with 4 questions, and then one global Pain Intensity item. The domains include: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. The global item domain is Pain Intensity. Each PROMIS domain can range from a score of 4-20, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).&#xD;
The outcome measure for this endpoint is the change in the global item (Pain Intensity) from baseline. The Global Pain Intensity item can range from 0-10, with higher scores indicating more severe pain intensity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.24" spread="2.63"/>
                    <measurement group_id="O2" value="-0.95" spread="1.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.29" spread="2.55"/>
                    <measurement group_id="O2" value="-1.16" spread="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.19" spread="2.73"/>
                    <measurement group_id="O2" value="-1.74" spread="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The Work Productivity and Activity Impairment - Migraine (WPAI-M) is a 6-item self-administered questionnaire that measures work productivity and the amount of time missed from work due to migraine. Scores are based on a percentage, so the range of scores is 0-100%, with higher scores indicating greater impairment and less productivity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The Work Productivity and Activity Impairment - Migraine (WPAI-M) is a 6-item self-administered questionnaire that measures work productivity and the amount of time missed from work due to migraine. Scores are based on a percentage, so the range of scores is 0-100%, with higher scores indicating greater impairment and less productivity. Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.48" spread="25.39"/>
                    <measurement group_id="O2" value="-5.26" spread="23.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26.19" spread="24.59"/>
                    <measurement group_id="O2" value="-7.90" spread="26.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-24.76" spread="37.77"/>
                    <measurement group_id="O2" value="-14.21" spread="20.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12.</title>
        <description>The Brief Measure of Worry Severity (BMWS) is a 8-item, self-administered questionnaire that measures various components of dysfunctional worry. Score range from 0-24 with higher scores indicating more worry within the participant. Change = (Applicable Treatment Month Score - Baseline Score)</description>
        <time_frame>Baseline to Weeks 4, 8, and 12</time_frame>
        <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>AJOVY (Fremanezumab-vfrm) - Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
          <group group_id="O2">
            <title>AJOVY (Fremanezumab-vfrm) - Non-Responder</title>
            <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution&#xD;
Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with &lt; 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12.</title>
          <description>The Brief Measure of Worry Severity (BMWS) is a 8-item, self-administered questionnaire that measures various components of dysfunctional worry. Score range from 0-24 with higher scores indicating more worry within the participant. Change = (Applicable Treatment Month Score - Baseline Score)</description>
          <population>All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.57" spread="2.87"/>
                    <measurement group_id="O2" value="-0.05" spread="3.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.91" spread="2.53"/>
                    <measurement group_id="O2" value="-0.68" spread="4.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.05" spread="2.33"/>
                    <measurement group_id="O2" value="-1.63" spread="5.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AJOVY (Fremanezumab-vfrm)</title>
          <description>Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.&#xD;
Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]: 225 MG/1.5 ML Subcutaneous Solution</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (24.1)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator agrees to submit all manuscripts or abstracts to sponsor before submission. Sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jim Sly</name_or_title>
      <organization>Clinvest Research</organization>
      <phone>417-841-3673</phone>
      <email>jsly@clinvest.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04461795
org study id: 19-001TE
nct id: NCT04461795
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study is being conducted to evaluate the efficacy and safety of AJOVY
      (fremanezumab-vfrm) on interictal migraine related burden in adults.
This is a single group, multicenter, open-label study with a study population of patients who
      meet International Classification of Headache Disorders 3rd edition (ICHD-III) criteria for
      migraine with or without aura and have 4 to 22 migraine days per month. This is a
      single-group supportive care study with one arm and no masking. A maximum of 40 participants
      will be enrolled to study intervention. All participants in this single-group study will
      complete a 4-week run-in period. After the run-in period, eligible participants will be
      enrolled to study intervention and enter a 12-week treatment period.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: Comparison of the mean change from baseline in the frequency of migraine headache days per 28-day period ending with the cessation of treatment month 3. A migraine headache day will be defined as a calendar day (00:00 to 23:59) with 4 or more hours of migraine headache, fulfilling International Classification of Headache Disorders-3 criteria, and/or any headache of any duration with the use of migraine-specific acute medications(s) (i.e. ergot alkaloids, ergot combinations, opioids, triptans, combination analgesics [simple analgesics combined with opioids or barbiturate with or without caffeine]). Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The Neuro-QoL Sleep Disturbance Short Form (SDSF) is an 8-item, self-administered questionnaire which measures quality of sleep including difficulties and perception of sleep satisfaction. Possible scores range from 8 to 40, with higher scores indicating worse sleep habits. Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The General Self-Efficacy - Short Form (GSE-SF) is a 4 item, self-administered questionnaire where the participant is asked to rate their confidence in managing situations, problems, and events. Scores range from 4-20. Higher scores indicate the participant has more self-efficacy managing difficult situations. Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) has 7 domains each with 4 questions, and then one global Pain Intensity item. The domains include: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. The global item domain is Pain Intensity. Each PROMIS domain can range from a score of 4-20, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).
The outcome measure for this endpoint is the change in the global item (Pain Intensity) from baseline. The Global Pain Intensity item can range from 0-10, with higher scores indicating more severe pain intensity. Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The Work Productivity and Activity Impairment - Migraine (WPAI-M) is a 6-item self-administered questionnaire that measures work productivity and the amount of time missed from work due to migraine. Scores are based on a percentage, so the range of scores is 0-100%, with higher scores indicating greater impairment and less productivity. Change = (Applicable Treatment Month Score - Baseline Score)
measure: Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12.
time frame: Baseline to Weeks 4, 8, and 12
description: The Brief Measure of Worry Severity (BMWS) is a 8-item, self-administered questionnaire that measures various components of dysfunctional worry. Score range from 0-24 with higher scores indicating more worry within the participant. Change = (Applicable Treatment Month Score - Baseline Score)
arm group label: AJOVY (fremanezumab-vfrm)
arm group type: Experimental
description: Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks.
intervention type: Drug
intervention name: Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution [AJOVY]
description: 225 MG/1.5 ML Subcutaneous Solution
arm group label: AJOVY (fremanezumab-vfrm)
other name: fremanezumab-vfrm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: David True
role: Principal Investigator
affiliation: Clinvest Research
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Clinvest Research, LLC
investigator full name: David True
investigator title: Medical Director
mesh term: Migraine Disorders
mesh term: Erenumab
mesh term: Antibodies, Monoclonal
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 