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

Migraine Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03971071
• Other study ID #: 20170703
• Secondary ID: 2018-003342-16
• Status: Completed
• Phase: Phase 4
• Start date: October 7, 2019
• Est. completion date: June 13, 2023

Study information

• Verified date: February 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 620
• Est. completion date: June 13, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Headache Disorders, Secondary
• Migraine Disorders
• Migraine Headache
• Prescription Drug Overuse

Intervention

Drug:
• Erenumab 70 mg
Erenumab once every 4 weeks. Subcutaneous injection.
• Erenumab 140 mg
Erenumab once every 4 weeks. Subcutaneous injection.
• Placebo
Placebo once every 4 weeks. Subcutaneous injection.

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Austria	Medizinische Universitaet Innsbruck	Innsbruck
Austria	Klinikum Klagenfurt am Woerthersee	Klagenfurt
Austria	Konventhospital der Barmherzigen Brueder Linz	Linz
Austria	Universitaetsklinikum Allgemeines Krankenhaus Wien	Wien
Czechia	Fakultni nemocnice u svate Anny v Brne	Brno
Czechia	Neurologie Brno sro	Brno
Czechia	INEP	Praha
Czechia	Dado Medical sro	Praha 2
Czechia	Thomayerova nemocnice	Praha 4
Czechia	Mudr Stanislav Bartek sro	Prerov
Czechia	Vestra Clinics sro	Rychnov nad Kneznou
Finland	Helsingin Paansarkykeskus Aava	Helsinki
Finland	Northern Cinical Trial Coordinators	Oulu
Finland	Suomen Terveystalo	Tampere
Finland	Terveystalo Pulssi	Turku
France	Hospices Civils de Lyon - Hopital neurologique Pierre Wertheimer	Bron cedex
France	Centre Hospitalier Regional Universitaire de Lille - Hopital Roger Salengro	Lille
France	Hopital La Timone	Marseille cedex 05
France	Centre Hospitalier Universitaire de Nice - Hopital de Cimiez	Nice cedex 1
France	Groupe hospitalier Paris Saint Joseph	Paris
France	Hopital Lariboisiere	Paris
France	Centre Hospitalier Universitaire de Poitiers	Poitiers Cedex
France	Centre Hospitalier Annecy Genevois	Pringy Cedex
France	Centre Hospitalier Universitaire Saint-Etienne - Hopital Nord	Saint-Etienne cedex 2
Hungary	Jahn Ferenc Del-pesti Korhaz es Rendelointezet	Budapest
Hungary	Obudai Egeszsegugyi Centrum Kft	Budapest
Hungary	Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet	Budapest
Hungary	Swiss Premium Egeszsegkozpont	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
Italy	IRCCS Istituto delle Scienze Neurologiche di Bologna Ospedale Bellaria	Bologna
Italy	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Fondazione Istituto Neurologico Nazionale C Mondino IRCCS	Pavia
Italy	IRCCS San Raffaele Pisana	Roma
Poland	Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Spolka Jawna	Ksawerow
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
Portugal	Hospital Professor Doutor Fernando Fonseca, EPE	Amadora
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria	Lisboa
Portugal	Hospital da Luz, SA	Lisboa
Portugal	Campus Neurologico Senior	Torres Vedras
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Cataluña
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucía
Spain	Hospital Clinico Universitario de Valencia	Valencia	Comunidad Valenciana
Spain	Hospital Universitari i Politecnic La Fe	Valencia	Comunidad Valenciana
Spain	Hospital Clinico Universitario de Valladolid	Valladolid	Castilla León
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza	Aragón
United Kingdom	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 States	Dent Neurosciences Research Center	Amherst	New York
United States	Michigan Head Pain and Neurological Institute	Ann Arbor	Michigan
United States	Citizens Memorial Healthcare	Bolivar	Missouri
United States	Core Healthcare Group	Cerritos	California
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	Axiom Research	Colton	California
United States	Texas Neurology, PA	Dallas	Texas
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Neurology Center of New England PC	Foxboro	Massachusetts
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Marshall University	Huntington	West Virginia
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	Clinical Research Institute	Los Angeles	California
United States	Saint Lukes Clinic	Meridian	Idaho
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Floridian Clinical Research LLC	Miami Lakes	Florida
United States	Clinical Research Institute Inc	Minneapolis	Minnesota
United States	Nashville Neuroscience Group	Nashville	Tennessee
United States	DelRicht Research	New Orleans	Louisiana
United States	Clinical Neuroscience Solutions	Orlando	Florida
United States	College Park Family Care Center	Overland Park	Kansas
United States	Emerald Coast Center for Neurological Disorders	Pensacola	Florida
United States	Allegheny Health Network Cancer Institute at Mellon Pavilion	Pittsburgh	Pennsylvania
United States	Preferred Primary Care Physicians, Inc	Pittsburgh	Pennsylvania
United States	Collective Medical Research	Prairie Village	Kansas
United States	Mercy Research	Saint Louis	Missouri
United States	Wasatch Clinical Research LLC	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
United States	The George Washington Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)

External Links

•   AmgenTrials clinical trials website