Clinical trial NCT03971071: A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Migraine Headache
Keywords: Chronic Migraine
Medication Overuse Headache
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Absence of Medication Overuse Headaches (MOH) at Month 6
timeFrame: Months 4, 5, and 6 (weeks 13 through 24) of the DBTP
Secondary outcomes:
measure: Change From Baseline in Mean Monthly AHMDs Over Months 4, 5, and 6
timeFrame: Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
measure: Number of Participants With Sustained MOH Remission at Month 6
timeFrame: Month 3 (week 12) to month 6 (week 24) of the DBTP
measure: Change From Baseline in Mean Monthly Average Physical Impairment Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID)
timeFrame: Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
measure: Change From Baseline in Mean Monthly Average Impact on Everyday Activities Domain Scores as Measured by the MPFID
timeFrame: Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to Week 24 (DBTP) and Week 25 to 52 weeks (OLTP)
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: Core Healthcare Group
state: California
city: Colton
country: United States
facility: Axiom Research
state: California
city: Los Angeles
country: United States
facility: Clinical Research Institute
state: California
city: Washington
country: United States
facility: The George Washington Medical Faculty Associates
state: District of Columbia
city: Miami Lakes
country: United States
facility: Floridian Clinical Research LLC
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Pensacola
country: United States
facility: Emerald Coast Center for Neurological Disorders
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Meridian
country: United States
facility: Saint Lukes Clinic
state: Idaho
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Overland Park
country: United States
facility: College Park Family Care Center
state: Kansas
city: Prairie Village
country: United States
facility: Collective Medical Research
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Foxboro
country: United States
facility: Neurology Center of New England PC
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain and Neurological Institute
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute Inc
state: Minnesota
city: Bolivar
country: United States
facility: Citizens Memorial Healthcare
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Research
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: Charlotte
country: United States
facility: Onsite Clinical Solutions LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Clinical Trial Investigator Clinical Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network Cancer Institute at Mellon Pavilion
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc
state: Pennsylvania
city: Nashville
country: United States
facility: Nashville Neuroscience Group
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology, PA
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research LLC
state: Utah
city: Huntington
country: United States
facility: Marshall University
state: West Virginia
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Woerthersee
city: Linz
country: Austria
facility: Konventhospital der Barmherzigen Brueder Linz
city: Wien
country: Austria
facility: Universitaetsklinikum Allgemeines Krankenhaus Wien
city: Brno
country: Czechia
facility: Neurologie Brno sro
city: Brno
country: Czechia
facility: Fakultni nemocnice u svate Anny v Brne
city: Praha 2
country: Czechia
facility: Dado Medical sro
city: Praha 4
country: Czechia
facility: Thomayerova nemocnice
city: Praha
country: Czechia
facility: INEP
city: Prerov
country: Czechia
facility: Mudr Stanislav Bartek sro
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics sro
city: Helsinki
country: Finland
facility: Helsingin Paansarkykeskus Aava
city: Oulu
country: Finland
facility: Northern Cinical Trial Coordinators
city: Tampere
country: Finland
facility: Suomen Terveystalo
city: Turku
country: Finland
facility: Terveystalo Pulssi
city: Bron cedex
country: France
facility: Hospices Civils de Lyon - Hopital neurologique Pierre Wertheimer
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille - Hopital Roger Salengro
city: Marseille cedex 05
country: France
facility: Hopital La Timone
city: Nice cedex 1
country: France
facility: Centre Hospitalier Universitaire de Nice - Hopital de Cimiez
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Groupe hospitalier Paris Saint Joseph
city: Poitiers Cedex
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Pringy Cedex
country: France
facility: Centre Hospitalier Annecy Genevois
city: Saint-Etienne cedex 2
country: France
facility: Centre Hospitalier Universitaire Saint-Etienne - Hopital Nord
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft
city: Budapest
country: Hungary
facility: Swiss Premium Egeszsegkozpont
city: Budapest
country: Hungary
facility: Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-pesti Korhaz es Rendelointezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna Ospedale Bellaria
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale C Mondino IRCCS
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
city: Ksawerow
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska Spolka Jawna
city: Legionowo
country: Poland
facility: Jerzy Petz Mediq Niepubliczny Zaklad Opieki Zdrowotnej
city: Lodz
country: Poland
facility: Gabinet Lekarski Jacek Rozniecki
city: Poznan
country: Poland
facility: Clinical Research Center Spzoo Medic-R Spolka Komandytowa
city: Sochaczew
country: Poland
facility: RCMed Oddzial Sochaczew
city: Amadora
country: Portugal
facility: Hospital Professor Doutor Fernando Fonseca, EPE
city: Lisboa
country: Portugal
facility: Hospital da Luz, SA
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
city: Torres Vedras
country: Portugal
facility: Campus Neurologico Senior
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucía
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
state: Aragón
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
state: Castilla León
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College London
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: