Erenumab - Comprehensive Assessment of Efficacy in (High-Frequency) Episodic Migraine (EMBRACE)

Comprehensive Assessment of Erenumab Efficacy in Subjects With High Frequency Episodic Migraine With at Least 1 Previously Failed Preventive Treatment: a Global, Double-blind, Placebo-controlled Phase 4 Study

The primary objective of this study is to evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Erenumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment - Dr Georgi Stranski EAD
  • Plovdiv, Bulgaria, 4001
    • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Alexandrovska EAD
  • Sofia, Bulgaria, 1407
    • Medical Center Excelsior OOD
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital for Active Treatment in neurology and psychiatry Sveti Naum EAD
  • Sofia, Bulgaria, 1154
    • University First Multiprofile Hospital for Active Treatment - Sofia Sveti Yoan Krastitel EAD
  • Stara Zagora, Bulgaria, 6000
    • Medical Center New Rehabilitation Center EOOD
• Czechia
  • Brno, Czechia, 616 00
    • Neurologie Brno sro
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u svate Anny v Brne
  • Choceň, Czechia, 565 01
    • Poliklinika Chocen, Neurohk sro
  • Kladno, Czechia, 272 01
    • Brain-soultherapy sro
  • Prague, Czechia, 120 00
    • Dado Medical sro
  • Prague, Czechia, 186 00
    • Institut neuropsychiatricke pece
  • Prague, Czechia, 160 00
    • FORBELI sro
  • Zlín, Czechia, 760 01
    • NeuroMed Zlin sro
• Hungary
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft
  • Budapest, Hungary, 1145
    • Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet
  • Budapest, Hungary, 1135
    • Uno Medical Trials Kft
  • Budapest, Hungary, 1064
    • High Tech Medical Kft
  • Budapest, Hungary, 1138
    • S-Medicon Kutatasi Centrum
  • Zalaegerszeg, Hungary, 8900
    • Obudai Egeszsegugyi Centrum Kft
• Italy
  • Bologna, Italy, 40139
    • Ospedale Bellaria Carlo Alberto Pizzardi
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Teritoriale Spedali Civili di Brescia
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliera Universitaria Renato Dulbecco
  • Genoa, Italy, 16132
    • Ospedale Policlinico San Martino IRCCS
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Nazionale C Mondino IRCCS
  • Roma, Italy, 00163
    • IRCCS San Raffaele Pisana
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Biomedico
  • Torino, Italy, 10126
    • Azienda della scienza di Torino
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House Spzoo
  • Gliwice, Poland, 44-100
    • Gabinet Diagnostyki i Leczenia Osteoporozy Prof Wojciech Pluskiewicz
  • Katowice, Poland, 40-568
    • Care Clinic Spzoo Care Clinic Centrum Medyczne
  • Katowice, Poland, 40-748
    • Vita Longa Spzoo
  • Kraśnik, Poland, 23-210
    • NZOZ Neuromed M i M Nastaj Spolka Partnerska
  • Lodz, Poland, 90-349
    • AppleTreeClinics Network Spzoo
  • Lodz, Poland, 91-072
    • M-Zdrowie
  • Lublin, Poland, 20-064
    • NZOZ Neuromed M i M Nastaj Spolka Partnerska
  • Oświęcim, Poland, 32-600
    • Instytut Zdrowia Dr Boczarska-Jedynak Spzoo SpKom
  • Poznan, Poland, 61-360
    • Osrodek Badan Klinicznych CROMED
  • Rzeszów, Poland, 35-301
    • Prywatny Gabinet Neurologiczny Iwona Rosciszewska-Zukowska
  • Wroclaw, Poland, 52-416
    • Centrum Medyczne Oporów
  • Wroclaw, Poland, 52-210
    • MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak
  • Wroclaw, Poland, 53-149
    • Vistamed and Vertigo Sp z o o
• Portugal
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz, SA
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar Universitario de Lisboa Norte, EPE - Hospital de Santa Maria
  • Sintra, Portugal, 2710-204
    • Hospital Cuf Sintra
  • Torres Vedras, Portugal, 2560-280
    • Campus Neurológico Sénior
• Romania
  • Bucharest, Romania, 050098
    • Spitalul Universitar de Urgență București
  • Bucharest, Romania, 010825
    • Spitalul Universitar de Urgenta Militar Central Dr. Carol Davila
  • Timișoara, Romania, 700736
    • Spitalul Clinic Judetean De Urgenta Pius Brinzeu Timisoara
• Spain
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Aragon
    • Zaragoza, Aragon, Spain, 50009
      • Hospital Clinico Universitario Lozano Blesa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
  • Castille and León
    • Valladolid, Castille and León, Spain, 47010
      • Hospital Clinico Universitario de Valladolid
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall d Hebron
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Hospital Universitari i Politecnic La Fe
    • Valencia, Valencia, Spain, 46010
      • Hospital Clinico Universitario de Valencia
• United States
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials Services Inc
    • Los Angeles, California, United States, 90048
      • Clinical Research Institute, LLC
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Mountain Neurological Research Center
    • Denver, Colorado, United States, 80210
      • Denver Neurological Clinic
    • Englewood, Colorado, United States, 80113
      • Summit Headache and Neurologic Institute
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33133
      • Visionary Investigators Network
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32819
      • Heuer Medical Doctor Research LLC
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Pembroke Pines, Florida, United States, 33026
      • Visionary Investigators Network
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Saint Lukes Clinic
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Chicago Headache Center and Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Worcester, Massachusetts, United States, 14226
      • New England Regional Headache Center Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65810
      • Clinvest Research LLC
    • St Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • Papillion Research Center
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Forte Family Practice
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • American Clinical Research Institute LLC
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Palmetto Clinical Trial Services
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Frisco, Texas, United States, 75034
      • North Texas Institute of Neurology and Headache

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria include:

• Age greater than or equal to 18 years upon entry into initial screening.
• Documented history of migraine with or without aura according to the International Headache Society (IHS) International Classification of Headache Disorders, Third Edition (ICHD-III) for greater than or equal to 12 months.
• Have high-frequency episodic migraine (HFEM): Defined as history of ≥ 7 to < 15 migraine days and < 15 headache days per month on average during the 3 months prior to screening.
• History of ≥ 4 migraine attacks of at least moderate severity per month on average during the 3 months prior to screening.
• History of treatment failure with at least 1 preventive treatment for migraine. Failure of preventive treatment for migraine is defined as treatment discontinuation due to lack of efficacy, adverse event, or general poor tolerability.
• Regular use of an oral triptan (using only eletriptan, rizatriptan, sumatriptan, or zolmitriptan) for acute migraine treatment, and typically initiating acute treatment with an oral triptan on > 50% of attacks of at least moderate pain intensity. Regular use is defined as ≥ 4 days of oral triptan use per month during the 3 months prior to screening.

Key exclusion criteria include:

• History of hemiplegic migraine, cluster headache, or other trigeminal autonomic cephalalgia.
• Has any medical contraindication to the use of an oral triptan.
• Previously treated with erenumab.

• Previously treated with a gepant (small molecule calcitonin gene related peptide receptor [CGRP-R] antagonist) in a preventive fashion in a manner consistent with migraine prevention that either:

  1. In the opinion of the investigator, did not offer any evidence of a therapeutic response or
  2. Was discontinued for less than 12 weeks from the date of initial screening or
  3. Was previously discontinued due to a known adverse drug reaction
• Currently being treated with lasmiditan and/or a gepant in the acute setting.
• No therapeutic response with greater than 4 of the defined medication categories after an adequate therapeutic trial.
• Currently has a history of consistent excellent response to oral triptans, defined as achievement of pain-freedom in ≤ 1 hour for ≥ 50% of treated attacks of at least moderate pain intensity during the 3 months prior to screening.
• Use of triptans administered via a non-oral (e.g. subcutaneous [SC] or intranasal delivery systems) or sublingual route at the time of screening, during the run-in and baseline periods, and throughout the study duration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erenumab; The 4-month DBTP has 2 phases: Main double-blind treatment phase (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment.; Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden.	Drug: Erenumab; 140 mg, 2 consecutive injections of 70 mg
Experimental: Placebo; The 4-month DBTP has 2 phases: Main DBTP (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment.; Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden.	Drug: Placebo; 2 consecutive injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Hours of at Least Moderate Headache Pain Intensity Over Months 1, 2, and 3	At least moderate headache pain intensity was defined as headache pain intensity reported as 'Moderate' or 'Severe' based on the 3-level headache pain intensity scale. Worst or peak pain intensity during a headache was collected using the e-diary in 3-levels (mild, moderate or severe). The duration of headaches with at least moderate pain intensity was collected. A negative change from baseline indicates a reduction in mean monthly hours of at least moderate headache pain intensity. Change from baseline in mean monthly measurement is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The least squares mean (LSM) estimates of change from baseline in reported headache pain intensity utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly Physical Function Domain Score as Measured by the Migraine Functional Impact Questionnaire (MFIQ) Over Months 1, 2, and 3	The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including on Physical Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the past 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3
Change From Baseline in Mean Monthly Usual Activities Domain Score as Measured by the MFIQ Over Months 1, 2, and 3	The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Usual Activities (10 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3
Change From Baseline in Mean Monthly Emotional Functioning Domain Score as Measured by the MFIQ Over Months 1, 2, and 3	The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Emotional Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3
Change From Baseline in Mean Monthly Social Functioning Domain Score as Measured by the MFIQ Over Months 1, 2, and 3	The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Social Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3
Change From Baseline in Mean Monthly Average Duration of at Least Moderate Headache Pain Intensity in Migraine Attacks Occurring Over Months 1, 2, and 3	At least moderate headache pain intensity was defined as headache pain intensity reported as 'Moderate' or 'Severe' based on the 3-level headache pain intensity scale. Worst or peak pain intensity during a headache was collected using the e-diary in 3-levels (mild, moderate or severe). The duration of headaches with at least moderate pain intensity during a migraine attack was collected. A negative change from baseline indicates a reduction in mean monthly average duration of at least moderate headache pain intensity during a migraine attack. Change from baseline in mean monthly measurement is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3
Change From Baseline in Mean Monthly Average Peak Migraine Pain Intensity as Assessed by the 11-point Numeric Rating Scale (NRS) Over Months 1, 2, and 3	The NRS assesses headache pain intensity ranging from 0 to 10 with a higher score indicating more severe pain. Participants recorded the pain intensity using the e-diary at the headache end-time or in an evening diary entry on a daily basis for an ongoing headache. A negative change from baseline indicates an improvement in pain intensity. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.	Baseline, Month 1, Month 2, and Month 3

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Paiva da Silva Lima G, Rao R, Szabó G, Szklener S, Tassorelli C, Nastaj M, Chou DE, Khodavirdi AC, Chehrenama M, Zhu Y, Bhatia AK, Dodick DW. Comprehensive assessment of erenumab efficacy in participants with high-frequency episodic migraine with at least one previously failed preventive treatment: The EMBRACE study. Headache. 2025 Oct 14.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2020
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): October 26, 2023

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; erenumab
• Other Study ID Numbers: 20190008; 2019-003646-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) 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 Sharing 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 Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No