Clinical trial NCT03927144: Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients
Official title: A 12-month Prospective, Randomized, Interventional, Global, Multi-center, Active-controlled Study Comparing Sustained Benefit of Two Treatment Paradigms (AMG334 qm vs. Oral Prophylactics) in Adult Episodic Migraine Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Episodic Migraine
Keywords: Erenumab
AMG334
Migraine
Episodic
Headache
CGRP
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2019-04-25
Enrollment: 621
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the sustained long-term benefit between two treatment paradigms of migraine prophylactic agents (erenumab versus a control arm of oral prophylactics) in episodic migraine patients who have previously failed 1 to 2 prophylactic migraine treatments.


Eligibility criteria: Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Adults greater than or equal to 18 years of age upon entry into screening.
* Documented history of migraine (with or without aura) greater than or equal to 12 months prior to screening according to the International Classification of Headache Disorders-3rd Edition (ICHD-3).
* Greater than or equal to 4 and less than 15 days per month of migraine symptoms (based on ICHD-3 criteria) on average across 3 months prior to screening based on retrospective reporting.
* Less than 15 days per month of headache symptoms (i.e., migraine and non-migraine).
* Subjects in need for switching by documented failure of 1 or 2 prophylactic treatments in the last 6 months due to either lack of efficacy or poor tolerability. For subjects with 1 prior treatment failure, the failure should have occurred in the last 6 months. For subjects with 2 prior treatment failures, the second treatment failure should have occurred in the last 6 months.
* During baseline: Confirmed migraine frequency of 4 to 14 migraine days and less than 15 days of headache symptoms.
* During baseline: greater than or equal to 80% compliance with the headache diary.

Exclusion Criteria:

* Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  * Older than 50 years of age at migraine onset.
  * History of cluster headache or hemiplegic migraine headache.
  * Unable to differentiate migraine from other headaches.
  * Lack of efficacy or poor tolerability with greater than 2 treatments from the 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial.
* Efficacy failure is defined as no meaningful reduction in headache frequency, duration, and/or severity after administration of the medication for at least 6 weeks at the generally accepted therapeutic dose(s) based on the investigator's assessment.
* Tolerability failure is defined as documented discontinuation due to adverse events of the respective medication during the last 6 months prior to screening.
* The following scenarios do not constitute lack of therapeutic response:
* Lack of sustained response to a medication.
* Patient decision to halt treatment due to improvement.
* Used a prohibited medication from the 7 categories of prior prophylactic medications within 3 months prior to the start of and during baseline for a non-migraine indication if dose is not stable
* Exposure to botulinum toxin in the head and/or neck region within 4 months.
* Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:

  * Ergotamines or triptans on greater than or equal to 10 days per month, or Simple analgesics (non-steroidal anti-inflammatory drugs \[NSAIDs\], acetaminophen) on greater than or equal to 15 days per month, or
  * Opioid- or butalbital-containing analgesics on greater than or equal to 4 days per month.
* Device, or procedure that potentially may interfere with the intensity or number of migraine days within 2 months prior to the start of or during baseline.
* History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or current evidence of depression. Subjects with anxiety disorder and/or major depressive disorders are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline period.
* History of seizure disorder or other significant neurological conditions other than migraine. Note: a single childhood febrile seizure is not exclusionary.
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
* Human immunodeficiency virus (HIV) infection by history.
* History or evidence of any other unstable or clinically significant medical condition or clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during that could pose a risk to subject safety or interfere with the study evaluation.
* Myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary artery bypass surgery or other re-vascularization procedures within 6 months prior to screening.
* Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
* Evidence of drug or alcohol abuse or dependence, based on Investigator discretion within 12 months.
* Pregnant or nursing (lactating) women.
* Women of child-bearing potential must use contraception during dosing with study treatment.
* Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
* History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
* Previous exposure to AMG334 or exposure to any other prophylactic CGRP-targeted therapy (prior to the study).

Primary outcomes:
measure: Number of Participants Who Completed Initially Assigned Treatment and Achieved at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 12
timeFrame: Baseline and Month 12
Secondary outcomes:
measure: Number of Participants Who Completed Initially Assigned Treatment at Month 12
timeFrame: Month 12
measure: Cumulative Mean Change From Baseline on the Monthly Migraine Days to Week 52
timeFrame: Baseline and Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, and Week 52
measure: Number of Responders as Measured by the Patient's Global Impression of Change (PGIC) Scale at Week 52
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Headache Center
state: California
city: New Haven
country: United States
facility: Yale Center for Clinical Research
state: Connecticut
city: Stamford
country: United States
facility: New England Institute for Neurology and Headache
state: Connecticut
city: Washington
country: United States
facility: George Washington Hospital
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Headache Division
state: Florida
city: West Palm Beach
country: United States
facility: Premier Research Institute
state: Florida
city: Chicago
country: United States
facility: Diamond Headache Clinic
state: Illinois
city: Riverwoods
country: United States
facility: Robbins Headache Clinic
state: Illinois
city: Watertown
country: United States
facility: Medvadis
state: Massachusetts
city: Worcester
country: United States
facility: New England Regional Headache Center, Inc
state: Massachusetts
city: Ann Arbor
country: United States
facility: MHNI
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute
state: Minnesota
city: Ridgeland
country: United States
facility: The Headache Center
state: Mississippi
city: Saint Louis
country: United States
facility: Mercy Health Research
state: Missouri
city: Saint Peters
country: United States
facility: Study Metrix Research
state: Missouri
city: Amherst
country: United States
facility: Laszlo Mechtler
state: New York
city: Philadelphia
country: United States
facility: Jefferson Headache Center
state: Pennsylvania
city: Nashville
country: United States
facility: Nashville Neuroscience Group
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Sherman
country: United States
facility: Texas Institute for Neurological Disorders
state: Texas
city: Buenos Aires
country: Argentina
facility: IDIM Instituto de Investigaciones Metabolicas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Mautalen Salud e Investigacion
city: Tucuman
country: Argentina
facility: Centro Medico Privado en Reumatologia
city: Innsbruck
country: Austria
facility: Univ. Klinik fuer Neurologie
city: Linz
country: Austria
facility: Ordensklinikum Linz Barmherzigen Schwestern
city: Vienna
country: Austria
facility: Univ Klinik fuer AKH
city: Brugge
country: Belgium
facility: AZ Sint Jan
city: Brussel
country: Belgium
facility: UZ Brussel
city: Gent
country: Belgium
facility: UZ Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Lier
country: Belgium
facility: Heilig Hart Ziekenhuis Lier
city: Brno
country: Czechia
facility: Neurologicka ambulance Quattromedica
city: Chocen
country: Czechia
facility: NEUROHK sro
city: Kladno
country: Czechia
facility: Brain Soultherapy sro
city: Prague
country: Czechia
facility: DADO Medical S R O
city: Prague
country: Czechia
facility: Institut neuropsychiatricke pece
city: Praha 10
country: Czechia
facility: Clintrial SRO
city: Praha 4
country: Czechia
facility: Thomayerova Nemocnice
city: Praha 6
country: Czechia
facility: Forbeli SRO
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics sro
city: Helsinki
country: Finland
facility: Terveystalo Ruoholahti
city: Helsinki
country: Finland
facility: Laakarikeskus Aava Itakeskus
city: Turku
country: Finland
facility: Terveystalo Pulssi
city: LILLE Cedex
country: France
facility: CHRU de LILLE
city: Paris cedex 10
country: France
facility: Hopital Lariboisiere Centre d Urgence des Cephalees
city: Rouen
country: France
facility: Hopital Charles Nicolle Departement de Neurologie
city: Saint Brieuc
country: France
facility: CH Yves Le Foll
city: SAINT ETIENNE cedex 2
country: France
facility: CHU St Etienne Hopital Nord Bat A
city: Bochum
country: Germany
facility: GP Dept of Neurology
city: Dortmund
country: Germany
facility: Neurologische Gemeinschaftspraxis Klemt & Bauersachs
city: Frankfurt
country: Germany
facility: Neurologische Gemeinschaftpraxis im Bienenkorbhaus
city: Leipzig
country: Germany
facility: AmBeNet Hausarztpraxis
city: Leipzig
country: Germany
facility: Medamed GmbH Studienambulanz
city: Athens
country: Greece
facility: Navy Hospital of Athens "NNA" Main Centre
city: Athens
country: Greece
facility: Aeginition Hospital of Athens, University of Athens
city: Athens
country: Greece
facility: Neurologicka Ambulancia Konzilium s r o
city: Athens
country: Greece
facility: 401 Army General Hospital of Athens Main Centre
city: Glyfada
country: Greece
facility: MEDITERRANEO Hospital
city: Patra
country: Greece
facility: General Hospital of Patra O AGIOS ANDREAS Neurology Clinic
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki Neurology Dept
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Dublin 9
country: Ireland
facility: Beaumont Hospital
city: Hadera
country: Israel
facility: Hillel Yaffe MC
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Netanya
country: Israel
facility: Laniado
city: Ramat Gan
country: Israel
facility: Sheba MC
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center Ichilov
city: Perugia
country: Italy
facility: A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte
state: PG
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
state: RM
city: Ancona
country: Italy
facility: Ospedali Riuniti Torrette di Ancona
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia Univ degli Studi
city: Roma
country: Italy
facility: Policl.Universit.Campus Bio-Medico Università Campus Bio-Med U.O.C.Area di Oncologia Medica
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea - Università La Sapienza
city: Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital Dept of Neurology C-70
city: Zwolle
country: Netherlands
facility: Isala Ziekenhuis
city: Krakow
country: Poland
facility: Centrum Leczenia Padaczki i Migreny
city: Lodz
country: Poland
facility: Gabient Lekarski Jacek Rozniecki
city: Warszawa
country: Poland
facility: OHA MED Sp zo o
city: Warszawa
country: Poland
facility: ETG Warszawa
city: Warszawa
country: Poland
facility: Wojskowy Instutyt Medyczny CSK MON
city: Almada
country: Portugal
facility: Hospital Garcia de Orta EPE
city: Lisboa
country: Portugal
facility: Hospital da Luz
city: Lisboa
country: Portugal
facility: Hospital Santa Maria
city: Matosinhos
country: Portugal
facility: Hospital Pedro Hispano Matosinhos E P E
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto Hospital Geral de Santo Antonio Serviço de Neurologia
city: Banska Bystrica
country: Slovakia
facility: MUDr Beata Dupejova s r o
city: Bratislava
country: Slovakia
facility: Nemocnica sv Michala a s
city: Komarno
country: Slovakia
facility: Nemocnica Komarno s r o
city: Levoca
country: Slovakia
facility: Neurologicke oddelenie VNsP Levoca
city: Liptovsky Mikulas
country: Slovakia
facility: Neurolog odd NsP Liptovsky Mikulas
city: Presov
country: Slovakia
facility: Neurologicka a algeziologicka ambulancia SANERA s r o
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucia
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Clinico Universitario Valencia
state: Communidad Valencia
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
state: Galicia
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron Madrid
state: Madrid
city: Madrid
country: Spain
facility: Hospital La Paz
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Edgbaston
country: United Kingdom
facility: Queen Elizabeth Hospital Pharmacy Dept.
state: Birmingham
city: Headington
country: United Kingdom
facility: The John Radcliffe Hospital
state: Oxfordshire
city: Stoke on Trent
country: United Kingdom
facility: University Hospital of North Midlands NHS Trust
state: Staffordshire
city: Glasgow
country: United Kingdom
facility: Glasgow Clinical Research Facility
city: Hull
country: United Kingdom
facility: Hull and amp East Yorkshire Hospitals NHS Trust
city: London
country: United Kingdom
facility: St Thomas Hospital
city: London
country: United Kingdom
facility: King's College Hospital London
city: Newcastile Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: