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Episodic MigrainePhase 4NCT03927144

Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

A Phase 4 study testing AMG334 and Oral Prophylactic in people with Episodic Migraine, run by Amgen at 112 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Episodic Migraine
What is being tested?
AMG334 and Oral Prophylactic
Could I receive a placebo?
No, everyone receives an active treatment
How many people
621 participants
Where
112 sitesin 18 countries
Study dates
15 May 2019to 30 Sep 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 29Show fewer
  • 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).

Trial locations and contacts

112 sites in 18 countries.

112 sites in 18 countries

United States20 sites

  • Laszlo Mechtler

    Amherst, New York, 14226

  • MHNI

    Ann Arbor, Michigan, 48104

  • Diamond Headache Clinic

    Chicago, Illinois, 60642

  • Study Metrix Research

    City of Saint Peters, Missouri, 63303

  • Texas Neurology

    Dallas, Texas, 75214

  • University of Miami Headache Division

    Miami, Florida, 33136

  • Clinical Research Institute

    Minneapolis, Minnesota, 55402

  • Nashville Neuroscience Group

    Nashville, Tennessee, 37203

  • Yale Center for Clinical Research

    New Haven, Connecticut, 06519

  • Jefferson Headache Center

    Philadelphia, Pennsylvania, 19107

  • The Headache Center

    Ridgeland, Mississippi, 38157

  • Robbins Headache Clinic

    Riverwoods, Illinois, 60015

  • Texas Institute for Neurological Disorders

    Sherman, Texas, 75092

  • Mercy Health Research

    St Louis, Missouri, 63141

  • New England Institute for Neurology and Headache

    Stamford, Connecticut, 06905

  • Stanford Headache Center

    Stanford, California, 94305

  • George Washington Hospital

    Washington D.C., District of Columbia, 20037

  • Medvadis

    Watertown, Massachusetts, 02472

  • Premier Research Institute

    West Palm Beach, Florida, 33407

  • New England Regional Headache Center, Inc

    Worcester, Massachusetts, 01605

Other trials in United States

Czechia9 sites

  • Neurologicka ambulance Quattromedica

    Brno, 602 00

  • NEUROHK sro

    Choceň, 56501

  • Brain Soultherapy sro

    Kladno, 272 01

  • DADO Medical S R O

    Prague, 120 00

  • Thomayerova Nemocnice

    Prague, 140 59

  • Forbeli SRO

    Prague, 160 00

  • Institut neuropsychiatricke pece

    Prague, 18600

  • Clintrial SRO

    Prague

  • Vestra Clinics sro

    Rychnov nad Kněžnou, 516 01

Other trials in Czechia

Spain9 sites

  • Hospital Vall D'Hebron

    Barcelona, Catalonia, 08035

  • Hospital La Paz

    Madrid, 28046

  • Hospital Quiron Madrid

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Marques de Valdecilla

    Santander, 39008

  • Hospital Clinico Universitario de Santiago

    Santiago de Compostela, Galicia, 15706

  • Hospital Universitario Virgen del Rocio

    Seville, Andalusia, 41013

  • Hospital Clinico Universitario Valencia

    Valencia, Communidad Valencia, 46010

  • Hospital Clinico Universitario de Valladolid

    Valladolid, Castille and León, 47011

  • Hospital Clinico Universitario Lozano Blesa

    Zaragoza, 50009

Other trials in Spain

United Kingdom9 sites

  • Queen Elizabeth Hospital Pharmacy Dept.

    Edgbaston, Birmingham, B15 2TH

  • Glasgow Clinical Research Facility

    Glasgow, G51 4TF

  • The John Radcliffe Hospital

    Headington, Oxfordshire, OX3 9DU

  • Hull and amp East Yorkshire Hospitals NHS Trust

    Hull, HU3 2JZ

  • St Thomas Hospital

    London, SE1 7EH

  • King's College Hospital London

    London, SE5 9RS

  • Royal Victoria Infirmary

    Newcastile Upon Tyne, NE1 4LP

  • Salford Royal Hospital

    Salford, M6 8HD

  • University Hospital of North Midlands NHS Trust

    Stoke-on-Trent, Staffordshire, ST46QG

Other trials in United Kingdom

Greece7 sites

  • Navy Hospital of Athens "NNA" Main Centre

    Athens, 115 21

  • Aeginition Hospital of Athens, University of Athens

    Athens, 115 28

  • Neurologicka Ambulancia Konzilium s r o

    Athens, 115 28

  • 401 Army General Hospital of Athens Main Centre

    Athens, 11525

  • MEDITERRANEO Hospital

    Glyfada, 16675

  • General Hospital of Patra O AGIOS ANDREAS Neurology Clinic

    Pátrai, 26335

  • Euromedica General Clinic of Thessaloniki Neurology Dept

    Thessaloniki, 54645

Other trials in Greece

Belgium6 sites

  • AZ Sint Jan

    Bruges, 8000

  • UZ Brussel

    Brussels, 1090

  • UZ Gent

    Ghent, 9000

  • Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie

    Hasselt, 3500

  • Centre Hospitalier Regional de la Citadelle

    Liège, 4000

  • Heilig Hart Ziekenhuis Lier

    Lier, 2500

Other trials in Belgium

Italy6 sites

  • Ospedali Riuniti Torrette di Ancona

    Ancona, 60126

  • ASST degli Spedali Civili di Brescia Univ degli Studi

    Brescia, 25100

  • A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte

    Perugia, PG, 06129

  • IRCCS San Raffaele Pisana

    Roma, RM, 00163

  • Policl.Universit.Campus Bio-Medico Università Campus Bio-Med U.O.C.Area di Oncologia Medica

    Roma, 00128

  • Azienda Ospedaliera Sant'Andrea - Università La Sapienza

    Roma, 00189

Other trials in Italy

Slovakia6 sites

  • MUDr Beata Dupejova s r o

    Banská Bystrica, 974 04

  • Nemocnica sv Michala a s

    Bratislava, 811 08

  • Nemocnica Komarno s r o

    Komárno, 945 75

  • Neurologicke oddelenie VNsP Levoca

    Levoča, 054 01

  • Neurolog odd NsP Liptovsky Mikulas

    Liptovský Mikuláš, 031 23

  • Neurologicka a algeziologicka ambulancia SANERA s r o

    Prešov, 08001

Other trials in Slovakia

France5 sites

  • CHRU de LILLE

    Lille, 59037

  • Hopital Lariboisiere Centre d Urgence des Cephalees

    Paris, 75010

  • Hopital Charles Nicolle Departement de Neurologie

    Rouen, 76031

  • CH Yves Le Foll

    Saint-Brieuc, 22000

  • CHU St Etienne Hopital Nord Bat A

    Saint-Etienne, 42055

Other trials in France

Germany5 sites

  • GP Dept of Neurology

    Bochum, D 44787

  • Neurologische Gemeinschaftspraxis Klemt & Bauersachs

    Dortmund, 44135

  • Neurologische Gemeinschaftpraxis im Bienenkorbhaus

    Frankfurt, 60313

  • AmBeNet Hausarztpraxis

    Leipzig, 04107

  • Medamed GmbH Studienambulanz

    Leipzig, 04109

Other trials in Germany

Israel5 sites

  • Hillel Yaffe MC

    Hadera, 38100

  • Rambam Medical Center

    Haifa, 31096

  • Laniado

    Netanya, 42150

  • Sheba MC

    Ramat Gan, 52621

  • Tel Aviv Sourasky Medical Center Ichilov

    Tel Aviv, 64239

Other trials in Israel

Poland5 sites

  • Centrum Leczenia Padaczki i Migreny

    Krakow, 31-209

  • Gabient Lekarski Jacek Rozniecki

    Lodz, 90 153

  • OHA MED Sp zo o

    Warsaw, 00 144

  • ETG Warszawa

    Warsaw, 02 777

  • Wojskowy Instutyt Medyczny CSK MON

    Warsaw, 04146

Other trials in Poland

Portugal5 sites

  • Hospital Garcia de Orta EPE

    Almada, 2801 951

  • Hospital da Luz

    Lisbon, 1500 650

  • Hospital Santa Maria

    Lisbon, 1600190

  • Hospital Pedro Hispano Matosinhos E P E

    Matosinhos Municipality, 4464-513

  • Centro Hospitalar do Porto Hospital Geral de Santo Antonio Serviço de Neurologia

    Porto, 4099-001

Other trials in Portugal

Netherlands4 sites

  • Zuyderland Medisch Centrum

    Geleen, 6162 BG

  • Martini Ziekenhuis

    Groningen, 9728 NT

  • Canisius Wilhelmina Hospital Dept of Neurology C-70

    Nijmegen, 6532 NZ

  • Isala Ziekenhuis

    Zwolle, 8025AB

Other trials in Netherlands

Argentina3 sites

  • IDIM Instituto de Investigaciones Metabolicas

    Buenos Aires, C1012AAR

  • Mautalen Salud e Investigacion

    Ciudad Autonoma de Bs As, C1128AAF

  • Centro Medico Privado en Reumatologia

    San Miguel de Tucumán, 4000

Other trials in Argentina

Austria3 sites

  • Univ. Klinik fuer Neurologie

    Innsbruck, A 6020

  • Ordensklinikum Linz Barmherzigen Schwestern

    Linz, 4010

  • Univ Klinik fuer AKH

    Vienna, 1090

Other trials in Austria

Finland3 sites

  • Terveystalo Ruoholahti

    Helsinki, 00180

  • Laakarikeskus Aava Itakeskus

    Helsinki, 00930

  • Terveystalo Pulssi

    Turku, 20100

Other trials in Finland

Ireland2 sites

  • Bon Secours Hospital

    Cork, T12 DV56

  • Beaumont Hospital

    Dublin, 47735

Other trials in Ireland

About this study

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

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.

Being tested
AMG334, Oral Prophylactic
Keywords
Erenumab, AMG334, Migraine, Episodic, Headache, CGRP
Medical subject headings
Migraine Disorders, Recurrence, Headache

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMG334Drug

    Also called Erenumab

    Subcutaneous Injection

  • Oral ProphylacticDrug

    SOC Oral Tablet/Capsule

Study groups in NCT03927144
Study groupRoleWhat they receive
AMG334 70 mg/140 mgExperimentalParticipants 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.
Receives: Drug: AMG334; Drug: Oral Prophylactic
Oral ProphylacticActive comparatorParticipants 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.
Receives: Drug: AMG334; Drug: Oral Prophylactic

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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:

    1. ≥2 of the following pain features:
    • Unilateral
    • Throbbing
    • Moderate to severe
    • Exacerbated with exercise/physical activity
    1. ≥1 of the following associated symptoms:
    • Nausea and/or vomiting
    • Photophobia 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.

    Measured: Baseline and Month 12

Secondary outcomes (3)

  1. Number of Participants Who Completed Initially Assigned Treatment at Month 12

    Measured: Month 12

  2. 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.

    Measured: 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

  3. 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.

    Measured: Baseline and Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2019
  2. Study start15 May 2019
  3. Primary completion1 Oct 2021
  4. Study completion30 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
621 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03927144
Sponsor's protocol ID
AMG334A2401
Other IDs
2018-001228-20, CAMG334A2401, 2018
Status last verified
Oct 2023
First submitted
23 Apr 2019
Last updated
18 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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

Publications

  • Pozo-Rosich P, Dolezil D, Paemeleire K, Stepien A, Stude P, Snellman J, Arkuszewski M, Stites T, Ritter S, Lopez Lopez C, Maca J, Ferraris M, Gil-Gouveia R. Early Use of Erenumab vs Nonspecific Oral Migraine Preventives: The APPRAISE Randomized Clinical Trial. JAMA Neurol. 2024 May 1;81(5):461-470. doi: 10.1001/jamaneurol.2024.0368.

    PubMed 38526461

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing AMG334 and Oral Prophylactic in people with Episodic Migraine, run by Amgen at 112 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 112 sites in United States, Czechia, Spain, United Kingdom, Greece and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03927144, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

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