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

NCT ID: NCT03971071

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 620 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-07
• Study Completion Date: 2023-06-13

Brief Summary

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).

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.

Conditions

Migraine Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo once every 4 weeks. Subcutaneous injection.

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.

Group Type: ACTIVE_COMPARATOR

Erenumab 70 mg

Intervention Type: DRUG

Erenumab once every 4 weeks. Subcutaneous injection.

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.

Group Type: ACTIVE_COMPARATOR

Erenumab 140 mg

Intervention Type: DRUG

Erenumab once every 4 weeks. Subcutaneous injection.

Interventions

Erenumab 70 mg

Erenumab once every 4 weeks. Subcutaneous injection.

Intervention Type: DRUG

Erenumab 140 mg

Erenumab once every 4 weeks. Subcutaneous injection.

Intervention Type: DRUG

Placebo

Placebo once every 4 weeks. Subcutaneous injection.

Intervention Type: DRUG

Other Intervention Names

Aimovig; Aimovig

Eligibility Criteria

Inclusion Criteria

• 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

-≥ 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)

Exclusion Criteria

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Core Healthcare Group

Cerritos, California, United States

Axiom Research

Colton, California, United States

Clinical Research Institute

Los Angeles, California, United States

The George Washington Medical Faculty Associates

Washington D.C., District of Columbia, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

Floridian Clinical Research LLC

Miami Lakes, Florida, United States

Clinical Neuroscience Solutions

Orlando, Florida, United States

Emerald Coast Center for Neurological Disorders

Pensacola, Florida, United States

University of South Florida

Tampa, Florida, United States

Saint Lukes Clinic

Meridian, Idaho, United States

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

College Park Family Care Center

Overland Park, Kansas, United States

Collective Medical Research

Prairie Village, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

DelRicht Research

New Orleans, Louisiana, United States

Neurology Center of New England PC

Foxborough, Massachusetts, United States

Michigan Head Pain and Neurological Institute

Ann Arbor, Michigan, United States

Clinical Research Institute Inc

Minneapolis, Minnesota, United States

Citizens Memorial Healthcare

Bolivar, Missouri, United States

Mercy Research

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Dent Neurosciences Research Center

Amherst, New York, United States

Onsite Clinical Solutions LLC

Charlotte, North Carolina, United States

Clinical Trial Investigator Clinical Research Center

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Allegheny Health Network Cancer Institute at Mellon Pavilion

Pittsburgh, Pennsylvania, United States

Preferred Primary Care Physicians, Inc

Pittsburgh, Pennsylvania, United States

Nashville Neuroscience Group

Nashville, Tennessee, United States

Texas Neurology, PA

Dallas, Texas, United States

Wasatch Clinical Research LLC

Salt Lake City, Utah, United States

Marshall University

Huntington, West Virginia, United States

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Medizinische Universitaet Innsbruck

Innsbruck, , Austria

Klinikum Klagenfurt am Woerthersee

Klagenfurt, , Austria

Konventhospital der Barmherzigen Brueder Linz

Linz, , Austria

Universitaetsklinikum Allgemeines Krankenhaus Wien

Vienna, , Austria

Neurologie Brno sro

Brno, , Czechia

Fakultni nemocnice u svate Anny v Brne

Brno, , Czechia

Dado Medical sro

Prague, , Czechia

Thomayerova nemocnice

Prague, , Czechia

INEP

Prague, , Czechia

Mudr Stanislav Bartek sro

Přerov, , Czechia

Vestra Clinics sro

Rychnov nad Kněžnou, , Czechia

Helsingin Paansarkykeskus Aava

Helsinki, , Finland

Northern Cinical Trial Coordinators

Oulu, , Finland

Suomen Terveystalo

Tampere, , Finland

Terveystalo Pulssi

Turku, , Finland

Hospices Civils de Lyon - Hopital neurologique Pierre Wertheimer

Bron, , France

Centre Hospitalier Regional Universitaire de Lille - Hopital Roger Salengro

Lille, , France

Hopital La Timone

Marseille, , France

Centre Hospitalier Universitaire de Nice - Hopital de Cimiez

Nice, , France

Hopital Lariboisiere

Paris, , France

Groupe hospitalier Paris Saint Joseph

Paris, , France

Centre Hospitalier Universitaire de Poitiers

Poitiers, , France

Centre Hospitalier Annecy Genevois

Pringy, , France

Centre Hospitalier Universitaire Saint-Etienne - Hopital Nord

Saint-Etienne, , France

Obudai Egeszsegugyi Centrum Kft

Budapest, , Hungary

Swiss Premium Egeszsegkozpont

Budapest, , Hungary

Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet

Budapest, , Hungary

Jahn Ferenc Del-pesti Korhaz es Rendelointezet

Budapest, , Hungary

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, , Hungary

Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz

Miskolc, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar

Szeged, , Hungary

IRCCS Istituto delle Scienze Neurologiche di Bologna Ospedale Bellaria

Bologna, , Italy

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

Fondazione Istituto Neurologico Nazionale C Mondino IRCCS

Pavia, , Italy

IRCCS San Raffaele Pisana

Roma, , Italy

Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Spolka Jawna

Ksawerów, , Poland

Jerzy Petz Mediq Niepubliczny Zaklad Opieki Zdrowotnej

Legionowo, , Poland

Gabinet Lekarski Jacek Rozniecki

Lodz, , Poland

Clinical Research Center Spzoo Medic-R Spolka Komandytowa

Poznan, , Poland

RCMed Oddzial Sochaczew

Sochaczew, , Poland

Hospital Professor Doutor Fernando Fonseca, EPE

Amadora, , Portugal

Hospital da Luz, SA

Lisbon, , Portugal

Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, , Portugal

Campus Neurologico Senior

Torres Vedras, , Portugal

Hospital Universitario Virgen del Rocio

Seville, Andalusia, Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Aragon, Spain

Hospital Clinico Universitario de Valladolid

Valladolid, Castille and León, Spain

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, Spain

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Catalonia, Spain

Hospital Clinico Universitario de Valencia

Valencia, Valencia, Spain

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, Spain

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

The Walton Centre NHS Foundation Trust

Liverpool, , United Kingdom

Kings College London

London, , United Kingdom

Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

John Radcliffe Hospital

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Czechia; Finland; France; Hungary; Italy; Poland; Portugal; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 39283627 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 40838472 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2018-003342-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20170703

Identifier Type: -

Identifier Source: org_study_id