<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/NCT03812224</url>
  </required_header>
  <id_info>
    <org_study_id>20170609</org_study_id>
    <nct_id>NCT03812224</nct_id>
  </id_info>
  <brief_title>A Controlled Trial of Erenumab in Migraine Prevention</brief_title>
  <official_title>A Phase 3 Japanese Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</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>
      The purpose of this study was to assess the efficacy and safety of erenumab for prevention of&#xD;
      migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Migraine prevention is an area of a large unmet medical need, with existing therapies often&#xD;
      having modest efficacy and poor tolerability. Calcitonin gene-related peptide (CGRP) receptor&#xD;
      antagonism is a novel approach to migraine preventive therapy. Erenumab is a human monoclonal&#xD;
      antibody against canonical CGRP receptor. The present study is a phase 3 trial intended to&#xD;
      assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with&#xD;
      episodic migraine (EM) and chronic migraine (CM).&#xD;
&#xD;
      The study consists of a screening period (up to 7 weeks, including a 4-week baseline period),&#xD;
      a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP),&#xD;
      and an 8-week safety follow-up period (12 weeks after the last dose of investigational&#xD;
      product).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 12, 2019</start_date>
  <completion_date type="Actual">November 25, 2020</completion_date>
  <primary_completion_date type="Actual">March 16, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period</measure>
    <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
    <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia&#xD;
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP</measure>
    <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
    <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP</measure>
    <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
    <description>An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine).&#xD;
The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">261</enrollment>
  <condition>Migraine</condition>
  <arm_group>
    <arm_group_label>Erenumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants were to receive placebo to erenumab once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erenumab</intervention_name>
    <description>Administered by subcutaneous injection once a month</description>
    <arm_group_label>Erenumab</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>AMG 334</other_name>
    <other_name>Aimovig®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered by subcutaneous injection once a month</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has provided informed consent/assent prior to initiation of any study specific&#xD;
             activities/procedures.&#xD;
&#xD;
          -  Japanese subjects greater than or equal to 20 to less than or equal to 65 years of age&#xD;
             upon entry into screening.&#xD;
&#xD;
          -  History of migraine (with or without aura) for greater than or equal to 12 months&#xD;
             before screening according to the International Headache Society Classification ICHD-3&#xD;
             (Headache Classification Committee of the International Headache Society, 2018) based&#xD;
             on medical records and/or patient self-report&#xD;
&#xD;
          -  Migraine frequency: Chronic Migraine (CM) or Episodic Migraine (EM) over the 3 months&#xD;
             before screening based on the following criteria:&#xD;
&#xD;
               1. CM is defined as greater than or equal to 15 headache days per month of which&#xD;
                  greater than or equal to 8 headache days on average across the 3 months meet&#xD;
                  criteria as migraine days&#xD;
&#xD;
               2. EM is defined as less than 15 headache days per month of which at least 4 or more&#xD;
                  headache days on average across the 3 months meet criteria as migraine days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects greater than 50 years of age at migraine onset.&#xD;
&#xD;
          -  History of cluster headache or hemiplegic migraine headache.&#xD;
&#xD;
          -  Unable to differentiate migraine from other headaches.&#xD;
&#xD;
          -  Migraine with continuous pain, in which the subject does not experience any pain-free&#xD;
             periods (of any duration) during the 1 month before the screening period.&#xD;
&#xD;
          -  Malignancy, except non-melanoma skin cancers, cervical or breast ductal carcinoma in&#xD;
             situ within the last 5 years.&#xD;
&#xD;
        Other exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Matsuyama-shi</city>
        <state>Ehime</state>
        <zip>790-0925</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kasuga-shi</city>
        <state>Fukuoka</state>
        <zip>816-0802</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kasuga-shi</city>
        <state>Fukuoka</state>
        <zip>816-0824</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hiroshima-shi</city>
        <state>Hiroshima</state>
        <zip>730-0031</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hiroshima-shi</city>
        <state>Hiroshima</state>
        <zip>730-0845</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <zip>003-0003</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <zip>007-0836</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <zip>060-8570</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kobe-shi</city>
        <state>Hyogo</state>
        <zip>658-0064</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kahoku-gun</city>
        <state>Ishikawa</state>
        <zip>929-0342</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Morioka-shi</city>
        <state>Iwate</state>
        <zip>020-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Takamatsu-shi</city>
        <state>Kagawa</state>
        <zip>769-0103</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kagoshima-shi</city>
        <state>Kagoshima</state>
        <zip>892-0844</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kawasaki-shi</city>
        <state>Kanagawa</state>
        <zip>211-8588</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kawasaki-shi</city>
        <state>Kanagawa</state>
        <zip>216-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kochi-shi</city>
        <state>Kochi</state>
        <zip>780-8011</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kumamoto-shi</city>
        <state>Kumamoto</state>
        <zip>861-2101</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kumamoto-shi</city>
        <state>Kumamoto</state>
        <zip>862-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyoto-shi</city>
        <state>Kyoto</state>
        <zip>600-8811</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sendai-shi</city>
        <state>Miyagi</state>
        <zip>982-0014</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oita-shi</city>
        <state>Oita</state>
        <zip>870-0831</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>556-0017</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toyonaka-shi</city>
        <state>Osaka</state>
        <zip>560-0012</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saga-shi</city>
        <state>Saga</state>
        <zip>840-0806</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Iruma-gun</city>
        <state>Saitama</state>
        <zip>350-0495</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saitama-shi</city>
        <state>Saitama</state>
        <zip>338-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tokorozawa-shi</city>
        <state>Saitama</state>
        <zip>359-1141</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shizuoka-shi</city>
        <state>Shizuoka</state>
        <zip>420-0853</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shimotsuga-gun</city>
        <state>Tochigi</state>
        <zip>321-0293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chofu-shi</city>
        <state>Tokyo</state>
        <zip>182-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hachioji-shi</city>
        <state>Tokyo</state>
        <zip>192-0032</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minato-ku</city>
        <state>Tokyo</state>
        <zip>108-0075</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minato-ku</city>
        <state>Tokyo</state>
        <zip>108-8642</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shibuya-ku</city>
        <state>Tokyo</state>
        <zip>151-0051</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Shinjuku-ku</city>
        <state>Tokyo</state>
        <zip>160-0017</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tottori-shi</city>
        <state>Tottori</state>
        <zip>680-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yonago-shi</city>
        <state>Tottori</state>
        <zip>683-0033</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toyama-shi</city>
        <state>Toyama</state>
        <zip>930-0803</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hofu-shi</city>
        <state>Yamaguchi</state>
        <zip>747-0802</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yamaguchi-shi</city>
        <state>Yamaguchi</state>
        <zip>754-0002</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kai-shi</city>
        <state>Yamanashi</state>
        <zip>400-0124</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <reference>
    <citation>Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.</citation>
    <PMID>35272533</PMID>
  </reference>
  <reference>
    <citation>Hirata K, Takeshima T, Sakai F, Imai N, Matsumori Y, Tatsuoka Y, Numachi Y, Yoshida R, Peng C, Mikol DD, Lima GPDS, Cheng S. Early onset of efficacy with erenumab for migraine prevention in Japanese patients: Analysis of two randomized, double-blind, placebo-controlled studies. Brain Behav. 2022 Mar;12(3):e2526. doi: 10.1002/brb3.2526. Epub 2022 Feb 24.</citation>
    <PMID>35201674</PMID>
  </reference>
  <reference>
    <citation>Hiramatsu K, Onizuka Y, Hasebe M, Yoshida R, Numachi Y. Novel Drug for Migraine Prophylaxis: Mode of Action, Efficacy and Safety of Erenumab. Shinryo to Shinyaku (Med Cons New-Remed) 2021:58(11):797-832</citation>
  </reference>
  <reference>
    <citation>Hirata K, Sakai F, Takeshima T, Imai N, Matsumori Y, Yoshida R, Numachi Y, Peng C, Mikol DD, Cheng S. Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial. J Headache Pain. 2021 Sep 18;22(1):110. doi: 10.1186/s10194-021-01313-8.</citation>
    <PMID>34537006</PMID>
  </reference>
  <reference>
    <citation>Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD. Erenumab treatment for migraine prevention in Japanese patients: Efficacy and safety results from a Phase 3, randomized, double-blind, placebo-controlled study. Headache. 2021 Jun;61(6):927-935. doi: 10.1111/head.14138. Epub 2021 Jun 21.</citation>
    <PMID>34153117</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <results_first_submitted>January 29, 2021</results_first_submitted>
  <results_first_submitted_qc>March 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 4, 2021</results_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erenumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either&#xD;
the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or&#xD;
clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.</ipd_access_criteria>
    <ipd_url>http://www.amgen.com/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03812224/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03812224/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 41 centers in Japan. The study consisted of a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP), followed by an 8-week safety follow-up (12 weeks after the last dose of investigational product).</recruitment_details>
      <pre_assignment_details>Eligible participants were randomized 1:1 to erenumab 70 mg or placebo. Randomization was stratified by migraine type (episodic migraine [EM] / chronic migraine [CM]) and migraine preventive treatment status (ever used [prior and/or current] or never used).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo QM</title>
          <description>Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
        </group>
        <group group_id="P2">
          <title>Erenumab 70 mg QM</title>
          <description>Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-blind Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="131"/>
                <participants group_id="P2" count="130"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="127"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Decision by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-label Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="127"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="125"/>
                <participants group_id="P2" count="124"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Decision by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The full analysis set (FAS) included all participants who were randomized in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo QM</title>
          <description>Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
        </group>
        <group group_id="B2">
          <title>Erenumab 70 mg QM</title>
          <description>Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="131"/>
            <count group_id="B2" value="130"/>
            <count group_id="B3" value="261"/>
          </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="44.6" spread="9.3"/>
                    <measurement group_id="B2" value="44.2" spread="8.5"/>
                    <measurement group_id="B3" value="44.4" spread="8.9"/>
                  </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="116"/>
                    <measurement group_id="B2" value="111"/>
                    <measurement group_id="B3" value="227"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="34"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="131"/>
                    <measurement group_id="B2" value="130"/>
                    <measurement group_id="B3" value="261"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="131"/>
                    <measurement group_id="B2" value="130"/>
                    <measurement group_id="B3" value="261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Migraine Type</title>
          <description>Episodic migraine is characterized by migraine with fewer than 15 headache days per month.&#xD;
Chronic migraine is characterized by 15 or more headache days per month (where at least 8 of those days are migraine days).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Episodic migraine</title>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="159"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic migraine</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior Migraine Preventive Treatment Status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Ever used (including prior and/or current users)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="100"/>
                    <measurement group_id="B2" value="100"/>
                    <measurement group_id="B3" value="200"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Never used</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Monthly Migraine Days</title>
          <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours and meeting protocol-specified criteria. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline period.</description>
          <units>days / month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.84" spread="5.70"/>
                    <measurement group_id="B2" value="12.40" spread="5.99"/>
                    <measurement group_id="B3" value="12.12" spread="5.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period</title>
        <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia&#xD;
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.</description>
        <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
        <population>The efficacy analysis set included randomized participants who received at least 1 dose of investigational product and had at least 1 change from baseline measurement in MMD during the DBTP. Observed data.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo QM</title>
            <description>Participants received placebo once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
          <group group_id="O2">
            <title>Erenumab 70 mg QM</title>
            <description>Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period</title>
          <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia&#xD;
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.</description>
          <population>The efficacy analysis set included randomized participants who received at least 1 dose of investigational product and had at least 1 change from baseline measurement in MMD during the DBTP. Observed data.</population>
          <units>migraine days / month</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="128"/>
                <count group_id="O2" value="129"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.98" lower_limit="-2.72" upper_limit="-1.24"/>
                    <measurement group_id="O2" value="-3.60" lower_limit="-4.36" upper_limit="-2.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The primary endpoint was analyzed using a generalized linear mixed model which includes treatment, visit, treatment-by-visit interaction, stratification factors of migraine type and prior migraine preventive treatment status, and baseline value as covariates and assumes a first-order auto regression covariance structure.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Generalized Linear Mixed Model</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-1.62</param_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-2.52</ci_lower_limit>
            <ci_upper_limit>-0.73</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP</title>
        <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia</description>
        <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
        <population>Efficacy analysis set; participants with missing data were counted as non-responders.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo QM</title>
            <description>Participants received placebo once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
          <group group_id="O2">
            <title>Erenumab 70 mg QM</title>
            <description>Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP</title>
          <description>A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:&#xD;
≥ 2 of the following pain features:&#xD;
unilateral&#xD;
throbbing&#xD;
moderate to severe&#xD;
exacerbated with exercise/physical activity&#xD;
≥ 1 of the following associated symptoms:&#xD;
nausea&#xD;
vomiting&#xD;
photophobia and phonophobia</description>
          <population>Efficacy analysis set; participants with missing data were counted as non-responders.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="131"/>
                <count group_id="O2" value="130"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.8"/>
                    <measurement group_id="O2" value="31.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>Cochran-Mantel-Haenszel (CMH) test, stratified by stratification factors of migraine type and prior migraine preventive treatment status.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.33</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.29</ci_lower_limit>
            <ci_upper_limit>4.23</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP</title>
        <description>An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine).&#xD;
The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.</description>
        <time_frame>4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period</time_frame>
        <population>Efficacy analysis set; observed data</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo QM</title>
            <description>Participants received placebo once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
          <group group_id="O2">
            <title>Erenumab 70 mg QM</title>
            <description>Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP</title>
          <description>An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine).&#xD;
The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.</description>
          <population>Efficacy analysis set; observed data</population>
          <units>days / month</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="128"/>
                <count group_id="O2" value="129"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.10" lower_limit="-1.74" upper_limit="-0.46"/>
                    <measurement group_id="O2" value="-2.57" lower_limit="-3.21" upper_limit="-1.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Analysis utilizes a generalized linear mixed model which includes treatment, visit, treatment-by-visit interaction, stratification factors of migraine type (episodic migraine or chronic migraine) and prior migraine preventive treatment status (ever used or never used), and baseline value as covariates and assumes a first-order auto regression covariance structure.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Generalized Linear Mixed Model</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-1.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-2.24</ci_lower_limit>
            <ci_upper_limit>-0.71</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Double-blind Treatment Period: Placebo QM</title>
          <description>Participants received placebo once a month for 24 weeks during the double-blind treatment period.</description>
        </group>
        <group group_id="E2">
          <title>Double-blind Treatment Period: Erenumab 70 mg QM</title>
          <description>Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period.</description>
        </group>
        <group group_id="E3">
          <title>Open-label Treatment Period: Erenumab 70 mg QM</title>
          <description>Participants received erenumab 70 mg once a month for 28 weeks during the open-label treatment period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Brain contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Clavicle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Skull fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Meniscus injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Ovarian adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Laryngeal oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>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="40" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="62" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="49" subjects_at_risk="254"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="131"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="130"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="254"/>
              </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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.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/NCT03812224
org study id: 20170609
nct id: NCT03812224
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study was to assess the efficacy and safety of erenumab for prevention of
      migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).
Migraine prevention is an area of a large unmet medical need, with existing therapies often
      having modest efficacy and poor tolerability. Calcitonin gene-related peptide (CGRP) receptor
      antagonism is a novel approach to migraine preventive therapy. Erenumab is a human monoclonal
      antibody against canonical CGRP receptor. The present study is a phase 3 trial intended to
      assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with
      episodic migraine (EM) and chronic migraine (CM).

      The study consists of a screening period (up to 7 weeks, including a 4-week baseline period),
      a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP),
      and an 8-week safety follow-up period (12 weeks after the last dose of investigational
      product).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period
time frame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
description: A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
≥ 2 of the following pain features:
unilateral
throbbing
moderate to severe
exacerbated with exercise/physical activity
≥ 1 of the following associated symptoms:
nausea
vomiting
photophobia and phonophobia
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.
measure: Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP
time frame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
description: A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
≥ 2 of the following pain features:
unilateral
throbbing
moderate to severe
exacerbated with exercise/physical activity
≥ 1 of the following associated symptoms:
nausea
vomiting
photophobia and phonophobia
measure: Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP
time frame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
description: An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine).
The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.
arm group label: Erenumab
arm group type: Experimental
description: Participants were to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants were to receive placebo to erenumab once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.
intervention type: Drug
intervention name: Erenumab
description: Administered by subcutaneous injection once a month
arm group label: Erenumab
arm group label: Placebo
other name: AMG 334
other name: Aimovig®
intervention type: Drug
intervention name: Placebo
description: Administered by subcutaneous injection once a month
arm group label: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: Japan
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
citation: Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.
PMID: 35272533
citation: Hirata K, Takeshima T, Sakai F, Imai N, Matsumori Y, Tatsuoka Y, Numachi Y, Yoshida R, Peng C, Mikol DD, Lima GPDS, Cheng S. Early onset of efficacy with erenumab for migraine prevention in Japanese patients: Analysis of two randomized, double-blind, placebo-controlled studies. Brain Behav. 2022 Mar;12(3):e2526. doi: 10.1002/brb3.2526. Epub 2022 Feb 24.
PMID: 35201674
citation: Hiramatsu K, Onizuka Y, Hasebe M, Yoshida R, Numachi Y. Novel Drug for Migraine Prophylaxis: Mode of Action, Efficacy and Safety of Erenumab. Shinryo to Shinyaku (Med Cons New-Remed) 2021:58(11):797-832
citation: Hirata K, Sakai F, Takeshima T, Imai N, Matsumori Y, Yoshida R, Numachi Y, Peng C, Mikol DD, Cheng S. Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial. J Headache Pain. 2021 Sep 18;22(1):110. doi: 10.1186/s10194-021-01313-8.
PMID: 34537006
citation: Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD. Erenumab treatment for migraine prevention in Japanese patients: Efficacy and safety results from a Phase 3, randomized, double-blind, placebo-controlled study. Headache. 2021 Jun;61(6):927-935. doi: 10.1111/head.14138. Epub 2021 Jun 21.
PMID: 34153117
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Erenumab
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either
the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or
clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
ipd url: http://www.amgen.com/datasharing
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 