A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache

A Phase 4, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Chronic Migraine and Medication Overuse Headache

Study 20170703 is a phase 4, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of erenumab against placebo in participants with chronic migraine (CM) who have a history of at least 1 preventive treatment failure and are diagnosed with medication overuse headache (MOH).

Study Overview

• Status: Completed
• Conditions: Migraine Headache
• Intervention / Treatment: Drug: Placebo; Drug: Erenumab 70 mg; Drug: Erenumab 140 mg

Detailed Description

Study 20170703 is a phase 4, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the safety and efficacy of erenumab against placebo in a CM population with MOH and prior history of treatment failure. Participants will be enrolled based on fulfilment of the International Classification of Headache Disorders, 3rd Edition (ICHD-3) CM and MOH criteria and will not be advised to early discontinue acute medication.

Participants who successfully complete the 24-week double-blind treatment period (DBTP) of the study will be offered an opportunity to continue in an open-label treatment period (OLTP) of 28-weeks duration. Participants who received erenumab treatment during the DBTP will continue to receive the same erenumab dose during the OLTP. Participants who received placebo during the DBTP will be allocated in a 1:1 ratio to receive either erenumab 70 mg or 140 mg SC QM during the OLTP. All participants will remain blinded to their original DBTP treatment assignment.

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Woerthersee
  • Linz, Austria, 4021
    • Konventhospital der Barmherzigen Brueder Linz
  • Vienna, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
• Czechia
  • Brno, Czechia, 616 00
    • Neurologie Brno sro
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u svate Anny v Brne
  • Prague, Czechia, 140 59
    • Thomayerova nemocnice
  • Prague, Czechia, 120 00
    • Dado Medical sro
  • Prague, Czechia, 186 00
    • INEP
  • Přerov, Czechia, 750 02
    • Mudr Stanislav Bartek sro
  • Rychnov nad Kněžnou, Czechia, 516 01
    • Vestra Clinics sro
• Finland
  • Helsinki, Finland, 00930
    • Helsingin Paansarkykeskus Aava
  • Oulu, Finland, 90590
    • Northern Cinical Trial Coordinators
  • Tampere, Finland, 33100
    • Suomen Terveystalo
  • Turku, Finland, 20100
    • Terveystalo Pulssi
• France
  • Bron, France, 69677
    • Hospices Civils de Lyon - Hôpital Neurologique Pierre Wertheimer
  • Lille, France, 59037
    • Centre Hospitalier Régional Universitaire de Lille - Hôpital Roger Salengro
  • Marseille, France, 13385
    • Hôpital La Timone
  • Nice, France, 06003
    • Centre Hospitalier Universitaire de Nice - Hopital de Cimiez
  • Paris, France, 75010
    • Hopital Lariboisière
  • Paris, France, 75014
    • Groupe hospitalier Paris saint Joseph
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
  • Pringy, France, 74374
    • Centre Hospitalier Annecy Genevois
  • Saint-Etienne, France, 42055
    • Centre Hospitalier Universitaire Saint-Etienne - Hopital Nord
• Hungary
  • Budapest, Hungary, 1036
    • Obudai Egeszsegugyi Centrum Kft
  • Budapest, Hungary, 1123
    • Swiss Premium Egeszsegkozpont
  • Budapest, Hungary, 1145
    • Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet
  • Budapest, Hungary, 1204
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Debrecen, Hungary, 4026
    • Debreceni Egyetem Kenézy Gyula Egyetemi Kórház
  • Miskolc, Hungary, 3526
    • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
  • Szeged, Hungary, 6725
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
• Italy
  • Bologna, Italy, 40139
    • IRCCS Istituto delle Scienze Neurologiche di Bologna Ospedale Bellaria
  • Catanzaro, Italy, 88100
    • Azienda Ospedaliero Universitaria Mater Domini
  • Florence, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Nazionale C Mondino IRCCS
  • Roma, Italy, 00163
    • IRCCS San Raffaele Pisana
• Poland
  • Ksawerów, Poland, 95-054
    • Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Spolka Jawna
  • Legionowo, Poland, 05-120
    • Jerzy Petz Mediq Niepubliczny Zaklad Opieki Zdrowotnej
  • Lodz, Poland, 90-338
    • Gabinet Lekarski Jacek Rozniecki
  • Poznan, Poland, 60-848
    • Clinical Research Center Spzoo Medic-R Spolka Komandytowa
  • Sochaczew, Poland, 96-500
    • RCMed Oddzial Sochaczew
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Professor Doutor Fernando Fonseca, EPE
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz, SA
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
  • Torres Vedras, Portugal, 2560-280
    • Campus Neurologico Senior
• Spain
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Hospital Universitario Virgen del Rocío
  • Aragon
    • Zaragoza, Aragon, Spain, 50009
      • Hospital Clínico Universitario Lozano Blesa
  • Castille and León
    • Valladolid, Castille and León, Spain, 47010
      • Hospital Clínico Universitario de Valladolid
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall d Hebron
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Hospital Universitari i Politècnic La Fe
    • Valencia, Valencia, Spain, 46010
      • Hospital Clinico Universitario De Valencia
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Liverpool, United Kingdom, L9 7LJ
    • The Walton Centre NHS Foundation Trust
  • London, United Kingdom, SE5 9RS
    • Kings College London
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
• United States
  • California
    • Cerritos, California, United States, 90703
      • Core Healthcare Group
    • Colton, California, United States, 92324
      • Axiom Research
    • Los Angeles, California, United States, 90048
      • Clinical Research Institute
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • The George Washington Medical Faculty Associates
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research LLC
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions
    • Pensacola, Florida, United States, 32504
      • Emerald Coast Center For Neurological Disorders
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Saint Lukes Clinic
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center
    • Prairie Village, Kansas, United States, 66208
      • Collective Medical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • DelRicht Research
  • Massachusetts
    • Foxborough, Massachusetts, United States, 02035
      • Neurology Center of New England PC
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute Inc
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Citizens Memorial Healthcare
    • St Louis, Missouri, United States, 63141
      • Mercy Research
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Clinical Trial Investigator Clinical Research Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Health Network Cancer Institute at Mellon Pavilion
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology, PA
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research LLC
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall University
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Eligibility criteria will be evaluated during the up to 3-week screening period (part 1) and a 4-week baseline period (part 2). At the end of baseline period, participants who successfully met eligibility criteria will be randomized on study.

Key Inclusion Criteria Part 1: To be assessed during the 3-week screening period, prior to the baseline period. Participants are eligible to be included in the study only if all of the following criteria apply:

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures
• Age ≥ 18 years on entry into the study
• Documented history of migraine without aura and/or migraine with aura according to the ICHD-3 classification for ≥ 12 months at screening
• Documented history of CM for a minimal duration of 6 months before screening
• Current diagnosis of MOH
• History of treatment failure with at least 1 preventive treatment as defined as treatment discontinuation due to lack of efficacy, adverse event or general poor tolerability

Key Exclusion Criteria Part 1

Participants are excluded from the study if any of the following criteria apply:

Disease Related

• Age > 50 years at migraine onset or > 65 years at CM onset
• History of hemiplegic migraine, cluster headache or other trigeminal autonomic cephalalgia
• Current concomitant diagnosis of a secondary type of headache other than MOH
• No therapeutic response in prevention of migraine after an adequate therapeutic trial of > 3 preventive treatment categories
• Changes in drug regimen (ie, changes in dose or frequency of use) of an allowed migraine preventive medication within 2 months prior to start of baseline
• Received botulinum toxin in the head and/or neck region within 4 months prior to screening
• Documented history of treatment with an anti-calcitonin gene-related peptide product preventive treatment
• Anticipated to require any excluded medication/device or procedure during the study

Other Medical Conditions

• History or evidence of unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen's physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
• Evidence of "recreational use" of illicit drugs within 12 months prior to screening, based on medical records, self-report, or a positive drug test performed during screening.

Key Inclusion Criteria Part 2. To be assessed at the end of the baseline period and prior to enrollment into DBTP. Based on information collected through the electronic diary (eDiary) during the baseline period, the following requirements must be met:

-≥ 14 headache days during the 28-day baseline period out of which ≥ 8 headache days meet criteria as migraine days

• Observation of acute migraine medication overuse during the baseline period. Medication overuse at baseline is defined as:
• ≥ 10 days of combination treatment OR
• ≥ 10 days of short-acting opioids/opioid-containing medication OR
• ≥ 10 days of triptans, ergots, OR
• ≥ 15 days of nonsteroidal anti-inflammatory drugs or simple analgesics intake
• At least 2 acute headache medication days per week for each week with at least 5 diary days
• Demonstrated at least 80% compliance with the eDiary (eg, must complete eDiary items on at least 23 out of 28 days during the baseline period)

Key Exclusion Criteria Part 2

Study Procedures

• Changed or planning to change the dose of an allowed concomitant medication that may have migraine preventive effect during baseline period or post-randomization
• Unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

Contraception, pregnancy or breastfeeding

• Unwillingness to maintain acceptable contraception method, when applicable
• Evidence of pregnancy or breastfeeding per participant self-report, medical records or positivity on baseline pregnancy screening tests, through end of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.	Drug: Placebo; Placebo once every 4 weeks. Subcutaneous injection.
Active Comparator: Erenumab 70 mg; After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.	Drug: Erenumab 70 mg; Erenumab once every 4 weeks. Subcutaneous injection.; Other Names: Aimovig
Active Comparator: Erenumab 140 mg; After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.	Drug: Erenumab 140 mg; Erenumab once every 4 weeks. Subcutaneous injection.; Other Names: Aimovig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Absence of Medication Overuse Headaches (MOH) at Month 6	Absence of MOH at month 6 was defined as mean monthly acute headache medication days (AHMD) < 10 days over months 4, 5, and 6 (weeks 13 through 24) or mean monthly headache days < 14 days over months 4, 5, and 6 (weeks 13 through 24) of the DBTP where an AHMD was defined as a calendar day in which the participant took at least 1 acute headache medication.	Months 4, 5, and 6 (weeks 13 through 24) of the DBTP

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Monthly AHMDs Over Months 4, 5, and 6	An AHMD was defined as a calendar day in which the participant takes at least 1 acute headache medication. Acute headache medications included triptan-based, ergotamine-based and ditan-based migraine medications, non-opioid and opioid-containing acute headache medications, non-opioid butalbital and opioid-containing butalbital containing medications.	Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
Number of Participants With Sustained MOH Remission at Month 6	Sustained MOH remission was defined as the absence of MOH at month 3 (week 12) and month 6 (week 24) of the DBTP. Absence of MOH was achieved when mean monthly AHMD < 10 days or mean monthly headache days < 14 days over the 3-month period (weeks 12 to 24).	Month 3 (week 12) to month 6 (week 24) of the DBTP
Change From Baseline in Mean Monthly Average Physical Impairment Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID)	The MPFID is a self-administered 13-item instrument measuring physical functioning, completed daily using the eDiary. The physical impairment domain includes 5 items. Participants respond to items using a 5-point scale, with difficulty items ranging from "Without any difficulty" to "Unable to do", and frequency items ranging from "None of the time" to "All of the time". Each item is assigned a score from 1 to 5, with 5 representing the greatest burden. For each domain, the scores are calculated as the sum of the item responses and the sum is rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden.	Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
Change From Baseline in Mean Monthly Average Impact on Everyday Activities Domain Scores as Measured by the MPFID	The MPFID is a self-administered 13-item instrument measuring physical functioning, completed daily using the eDiary. The impact on everyday activities domain includes 7 items. Participants respond to items using a 5-point scale, with difficulty items ranging from "Without any difficulty" to "Unable to do", and frequency items ranging from "None of the time" to "All of the time". Each item is assigned a score from 1 to 5, with 5 representing the greatest burden. For each domain, the scores are calculated as the sum of the item responses and the sum is rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden.	Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs were defined as any adverse event (AE) that started on or after first dose of IP, and up to the end of the study (52 weeks). Any clinically significant changes in vital signs were included as TEAEs.	Day 1 to Week 24 (DBTP) and Week 25 to 52 weeks (OLTP)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Tepper SJ, Dodick DW, Lanteri-Minet M, Dolezil D, Gil-Gouveia R, Lucas C, Piasecka-Stryczynska K, Szabo G, Mikol DD, Chehrenama M, Chou DE, Yang Y, Paiva da Silva Lima G. Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine: A Phase 4, Randomized, Placebo-Controlled Trial. JAMA Neurol. 2024 Sep 16;81(11):1140-9. doi: 10.1001/jamaneurol.2024.3043. Online ahead of print.
• Tepper SJ, Dodick DW, Lanteri-Minet M, Dolezil D, Gil-Gouveia R, Lucas C, Piasecka-Stryczynska K, Szabo G, Mikol DD, Chehrenama M, Chou DE, Liu Z, da Silva Lima GP. Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache: Final Results From a Phase 4 Randomized Placebo-Controlled Study. Eur J Neurol. 2025 Aug;32(8):e70328. doi: 10.1111/ene.70328.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Migraine; Medication Overuse Headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache Disorders, Secondary; Substandard Drugs; Pharmaceutical Preparations; erenumab
• Other Study ID Numbers: 20170703; 2018-003342-16 (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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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 URL 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
• product manufactured in and exported from the U.S.: No