Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Drug: AMG334; Drug: Oral Prophylactic

• Study Type: Interventional
• Enrollment (Actual): 621
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • IDIM Instituto de Investigaciones Metabolicas
  • Ciudad Autonoma de Bs As, Argentina, C1128AAF
    • Mautalen Salud e Investigación
  • Tucuman, Argentina, 4000
    • Centro Medico Privado en Reumatologia
• Austria
  • Innsbruck, Austria, A 6020
    • Univ. Klinik fuer Neurologie
  • Linz, Austria, 4010
    • Ordensklinikum Linz Barmherzigen Schwestern
  • Vienna, Austria, 1090
    • Univ Klinik fuer AKH
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Gent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie
  • Liege, Belgium, 4000
    • Centre Hospitalier Regional de la Citadelle
  • Lier, Belgium, 2500
    • Heilig Hart Ziekenhuis Lier
• Czechia
  • Brno, Czechia, 602 00
    • Neurologicka ambulance Quattromedica
  • Chocen, Czechia, 56501
    • NEUROHK sro
  • Kladno, Czechia, 272 01
    • Brain Soultherapy sro
  • Prague, Czechia, 18600
    • Institut Neuropsychiatricke pece
  • Prague, Czechia, 120 00
    • DADO Medical S R O
  • Praha 10, Czechia
    • Clintrial sro
  • Praha 4, Czechia, 140 59
    • Thomayerova Nemocnice
  • Praha 6, Czechia, 160 00
    • Forbeli SRO
  • Rychnov nad Kneznou, Czechia, 516 01
    • Vestra Clinics sro
• Finland
  • Helsinki, Finland, 00180
    • Terveystalo Ruoholahti
  • Helsinki, Finland, 00930
    • Laakarikeskus Aava Itakeskus
  • Turku, Finland, 20100
    • Terveystalo Pulssi
• France
  • LILLE Cedex, France, 59037
    • CHRU de Lille
  • Paris cedex 10, France, 75010
    • Hopital Lariboisiere Centre d Urgence des Cephalees
  • Rouen, France, 76031
    • Hopital Charles Nicolle Departement de Neurologie
  • SAINT ETIENNE cedex 2, France, 42055
    • CHU St Etienne Hopital Nord Bat A
  • Saint Brieuc, France, 22000
    • CH Yves Le Foll
• Germany
  • Bochum, Germany, D 44787
    • GP Dept of Neurology
  • Dortmund, Germany, 44135
    • Neurologische Gemeinschaftspraxis Klemt & Bauersachs
  • Frankfurt, Germany, 60313
    • Neurologische Gemeinschaftpraxis im Bienenkorbhaus
  • Leipzig, Germany, 04107
    • AmBeNet Hausarztpraxis
  • Leipzig, Germany, 04109
    • Medamed GmbH Studienambulanz
• Greece
  • Athens, Greece, 115 21
    • Navy Hospital of Athens "NNA" Main Centre
  • Athens, Greece, 115 28
    • Aeginition Hospital of Athens, University of Athens
  • Athens, Greece, 115 28
    • Neurologicka Ambulancia Konzilium s r o
  • Athens, Greece, 11525
    • 401 Army General Hospital of Athens Main Centre
  • Glyfada, Greece, 16675
    • Mediterraneo Hospital
  • Patra, Greece, 26335
    • General Hospital of Patra O AGIOS ANDREAS Neurology Clinic
  • Thessaloniki, Greece, 54645
    • Euromedica General Clinic of Thessaloniki Neurology Dept
• Ireland
  • Cork, Ireland, T12 DV56
    • Bon Secours Hospital
  • Dublin 9, Ireland, 47735
    • Beaumont Hospital
• Israel
  • Hadera, Israel, 38100
    • Hillel Yaffe MC
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Netanya, Israel, 42150
    • Laniado
  • Ramat Gan, Israel, 52621
    • Sheba MC
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center Ichilov
• Italy
  • Ancona, Italy, 60126
    • Ospedali Riuniti Torrette di Ancona
  • Brescia, Italy, 25100
    • ASST degli Spedali Civili di Brescia Univ degli Studi
  • Roma, Italy, 00128
    • Policl.Universit.Campus Bio-Medico Università Campus Bio-Med U.O.C.Area di Oncologia Medica
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea - Università La Sapienza
  • PG
    • Perugia, PG, Italy, 06129
      • A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte
  • RM
    • Roma, RM, Italy, 00163
      • IRCCS San Raffaele Pisana
• Netherlands
  • Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum
  • Groningen, Netherlands, 9728 NT
    • Martini Ziekenhuis
  • Nijmegen, Netherlands, 6532 NZ
    • Canisius Wilhelmina Hospital Dept of Neurology C-70
  • Zwolle, Netherlands, 8025AB
    • Isala Ziekenhuis
• Poland
  • Krakow, Poland, 31-209
    • Centrum Leczenia Padaczki i Migreny
  • Lodz, Poland, 90 153
    • Gabient Lekarski Jacek Rozniecki
  • Warszawa, Poland, 00 144
    • OHA MED Sp zo o
  • Warszawa, Poland, 02 777
    • ETG Warszawa
  • Warszawa, Poland, 04146
    • Wojskowy Instutyt Medyczny CSK MON
• Portugal
  • Almada, Portugal, 2801 951
    • Hospital Garcia de Orta EPE
  • Lisboa, Portugal, 1500 650
    • Hospital da Luz
  • Lisboa, Portugal, 1600190
    • Hospital Santa Maria
  • Matosinhos, Portugal, 4464-513
    • Hospital Pedro Hispano Matosinhos E P E
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto Hospital Geral de Santo Antonio Serviço de Neurologia
• Slovakia
  • Banska Bystrica, Slovakia, 974 04
    • MUDr Beata Dupejova s r o
  • Bratislava, Slovakia, 811 08
    • Nemocnica sv Michala a s
  • Komarno, Slovakia, 945 75
    • Nemocnica Komarno s r o
  • Levoca, Slovakia, 054 01
    • Neurologicke oddelenie VNsP Levoca
  • Liptovsky Mikulas, Slovakia, 031 23
    • Neurolog odd NsP Liptovsky Mikulas
  • Presov, Slovakia, 08001
    • Neurologicka a algeziologicka ambulancia SANERA s r o
• Spain
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Santander, Spain, 39008
    • Hospital Marqués de Valdecilla
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Hospital Universitario Virgen del Rocio
  • Castilla Y Leon
    • Valladolid, Castilla Y Leon, Spain, 47011
      • Hospital Clínico Universitario de Valladolid
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Hospital Vall d'Hebron
  • Communidad Valencia
    • Valencia, Communidad Valencia, Spain, 46010
      • Hospital Clinico Universitario Valencia
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Hospital Clínico Universitario de Santiago
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron Madrid
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Glasgow Clinical Research Facility
  • Hull, United Kingdom, HU3 2JZ
    • Hull and amp East Yorkshire Hospitals NHS Trust
  • London, United Kingdom, SE1 7EH
    • St Thomas Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital London
  • Newcastile Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Salford, United Kingdom, M6 8HD
    • Salford Royal Hospital
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital Pharmacy Dept.
  • Oxfordshire
    • Headington, Oxfordshire, United Kingdom, OX3 9DU
      • The John Radcliffe Hospital
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom, ST46QG
      • University Hospital of North Midlands NHS Trust
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Headache Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Research
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Neurology and Headache
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Headache Division
    • West Palm Beach, Florida, United States, 33407
      • Premier Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60642
      • Diamond Headache Clinic
    • Riverwoods, Illinois, United States, 60015
      • Robbins Headache Clinic
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Medvadis
    • Worcester, Massachusetts, United States, 01605
      • New England Regional headache Center, Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • MHNI
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • Mississippi
    • Ridgeland, Mississippi, United States, 38157
      • The Headache Center
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
    • Saint Peters, Missouri, United States, 63303
      • Study Metrix Research
  • New York
    • Amherst, New York, United States, 14226
      • Laszlo Mechtler
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Headache Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group
  • Texas
    • Dallas, Texas, United States, 75214
      • Texas Neurology
    • Sherman, Texas, United States, 75092
      • Texas Institute for Neurological Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG334 70 mg/140 mg; Participants were randomized to receive 70 mg or 140 mg of AMG334 as a subcutaneous injection once per month for 52 weeks in the Core Phase. Participants were permitted to switch to an approved oral prophylactic based on treatment failure status and at the investigator's and participant's discretion. Participants who completed visits through Week 52 of the Core Phase were eligible to participate in the 52-week Extension Phase of the study.	Drug: AMG334; Subcutaneous Injection; Other Names: Erenumab; Drug: Oral Prophylactic; SOC Oral Tablet/Capsule
Active Comparator: Oral Prophylactic; Participants were randomized to receive a standard of care (SOC) locally approved oral prophylactic migraine medication once per day for 52 weeks in the Core Phase, as prescribed per local country labels. Participants were permitted to switch to a different approved oral prophylactic based on treatment failure status and at the investigator's and participant's discretion. Participants who completed visits through Week 52 of the Core Phase were eligible to participate in the 52-week Extension Phase of the study.	Drug: AMG334; Subcutaneous Injection; Other Names: Erenumab; Drug: Oral Prophylactic; SOC Oral Tablet/Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Completed Initially Assigned Treatment and Achieved at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 12	A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: ≥2 of the following pain features:UnilateralThrobbingModerate to severeExacerbated with exercise/physical activity; ≥1 of the following associated symptoms:Nausea and/or vomitingPhotophobia and phonophobia If the participant took a migraine-specific medication (ie, triptan or ergotamine) during aura, or to treat a headache on a calendar day, then it was counted as a migraine day regardless of the duration and pain features/associated symptoms. In addition to achieving at least a 50% reduction from baseline in monthly migraine days, participants must have also completed their initially assigned treatment through Month 12.	Baseline and Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Completed Initially Assigned Treatment at Month 12		Month 12
Cumulative Mean Change From Baseline on the Monthly Migraine Days to Week 52	A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). The mean of monthly migraine days was obtained cumulatively every 4 weeks across 52 weeks (for example, at Week 8 the mean will be based on data from Week 1 to Week 8; and at Week 12 the mean will be based on data from Week 1 to Week 12). The cumulative mean change from baseline in monthly migraine days was derived using difference between cumulative average of each month and baseline monthly migraine days.	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
Number of Responders as Measured by the Patient's Global Impression of Change (PGIC) Scale at Week 52	The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved (7) to no change or worsened condition (1). A responder was defined as a participant with a PGIC score of at least 5 (5=moderately better, 6=better, 7=a great deal better), at Week 52 for participants who completed the treatment period at Week 52 on the initially assigned treatment.	Baseline and Week 52

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Migraine; Headache; CGRP; AMG334; Erenumab; Episodic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: AMG334A2401; 2018-001228-20 (EudraCT Number); CAMG334A2401 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Data sharing for this study is the responsibility of Novartis. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No