Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

NCT ID: NCT03927144

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 621 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-15
• Study Completion Date: 2022-09-30

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.

Conditions

Episodic Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

AMG334

Intervention Type: DRUG

Subcutaneous Injection

Oral Prophylactic

Intervention Type: DRUG

SOC Oral Tablet/Capsule

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.

Group Type: ACTIVE_COMPARATOR

AMG334

Intervention Type: DRUG

Subcutaneous Injection

Oral Prophylactic

Intervention Type: DRUG

SOC Oral Tablet/Capsule

Interventions

AMG334

Subcutaneous Injection

Intervention Type: DRUG

Oral Prophylactic

SOC Oral Tablet/Capsule

Intervention Type: DRUG

Other Intervention Names

Erenumab

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Stanford Headache Center

Stanford, California, United States

Yale Center for Clinical Research

New Haven, Connecticut, United States

New England Institute for Neurology and Headache

Stamford, Connecticut, United States

George Washington Hospital

Washington D.C., District of Columbia, United States

University of Miami Headache Division

Miami, Florida, United States

Premier Research Institute

West Palm Beach, Florida, United States

Diamond Headache Clinic

Chicago, Illinois, United States

Robbins Headache Clinic

Riverwoods, Illinois, United States

Medvadis

Watertown, Massachusetts, United States

New England Regional Headache Center, Inc

Worcester, Massachusetts, United States

MHNI

Ann Arbor, Michigan, United States

Clinical Research Institute

Minneapolis, Minnesota, United States

The Headache Center

Ridgeland, Mississippi, United States

Study Metrix Research

City of Saint Peters, Missouri, United States

Mercy Health Research

St Louis, Missouri, United States

Laszlo Mechtler

Amherst, New York, United States

Jefferson Headache Center

Philadelphia, Pennsylvania, United States

Nashville Neuroscience Group

Nashville, Tennessee, United States

Texas Neurology

Dallas, Texas, United States

Texas Institute for Neurological Disorders

Sherman, Texas, United States

IDIM Instituto de Investigaciones Metabolicas

Buenos Aires, , Argentina

Mautalen Salud e Investigacion

Ciudad Autonoma de Bs As, , Argentina

Centro Medico Privado en Reumatologia

San Miguel de Tucumán, , Argentina

Univ. Klinik fuer Neurologie

Innsbruck, , Austria

Ordensklinikum Linz Barmherzigen Schwestern

Linz, , Austria

Univ Klinik fuer AKH

Vienna, , Austria

AZ Sint Jan

Bruges, , Belgium

UZ Brussel

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie

Hasselt, , Belgium

Heilig Hart Ziekenhuis Lier

Lier, , Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Neurologicka ambulance Quattromedica

Brno, , Czechia

NEUROHK sro

Choceň, , Czechia

Brain Soultherapy sro

Kladno, , Czechia

DADO Medical S R O

Prague, , Czechia

Thomayerova Nemocnice

Prague, , Czechia

Forbeli SRO

Prague, , Czechia

Institut neuropsychiatricke pece

Prague, , Czechia

Clintrial SRO

Prague, , Czechia

Vestra Clinics sro

Rychnov nad Kněžnou, , Czechia

Terveystalo Ruoholahti

Helsinki, , Finland

Laakarikeskus Aava Itakeskus

Helsinki, , Finland

Terveystalo Pulssi

Turku, , Finland

CHRU de LILLE

Lille, , France

Hopital Lariboisiere Centre d Urgence des Cephalees

Paris, , France

Hopital Charles Nicolle Departement de Neurologie

Rouen, , France

CH Yves Le Foll

Saint-Brieuc, , France

CHU St Etienne Hopital Nord Bat A

Saint-Etienne, , France

GP Dept of Neurology

Bochum, , Germany

Neurologische Gemeinschaftspraxis Klemt & Bauersachs

Dortmund, , Germany

Neurologische Gemeinschaftpraxis im Bienenkorbhaus

Frankfurt, , Germany

AmBeNet Hausarztpraxis

Leipzig, , Germany

Medamed GmbH Studienambulanz

Leipzig, , Germany

Navy Hospital of Athens "NNA" Main Centre

Athens, , Greece

Aeginition Hospital of Athens, University of Athens

Athens, , Greece

Neurologicka Ambulancia Konzilium s r o

Athens, , Greece

401 Army General Hospital of Athens Main Centre

Athens, , Greece

MEDITERRANEO Hospital

Glyfada, , Greece

General Hospital of Patra O AGIOS ANDREAS Neurology Clinic

Pátrai, , Greece

Euromedica General Clinic of Thessaloniki Neurology Dept

Thessaloniki, , Greece

Bon Secours Hospital

Cork, , Ireland

Beaumont Hospital

Dublin, , Ireland

Hillel Yaffe MC

Hadera, , Israel

Rambam Medical Center

Haifa, , Israel

Laniado

Netanya, , Israel

Sheba MC

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Center Ichilov

Tel Aviv, , Israel

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

Perugia, PG, Italy

IRCCS San Raffaele Pisana

Roma, RM, Italy

Ospedali Riuniti Torrette di Ancona

Ancona, , Italy

ASST degli Spedali Civili di Brescia Univ degli Studi

Brescia, , Italy

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

Roma, , Italy

Azienda Ospedaliera Sant'Andrea - Università La Sapienza

Roma, , Italy

Zuyderland Medisch Centrum

Geleen, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Canisius Wilhelmina Hospital Dept of Neurology C-70

Nijmegen, , Netherlands

Isala Ziekenhuis

Zwolle, , Netherlands

Centrum Leczenia Padaczki i Migreny

Krakow, , Poland

Gabient Lekarski Jacek Rozniecki

Lodz, , Poland

OHA MED Sp zo o

Warsaw, , Poland

ETG Warszawa

Warsaw, , Poland

Wojskowy Instutyt Medyczny CSK MON

Warsaw, , Poland

Hospital Garcia de Orta EPE

Almada, , Portugal

Hospital da Luz

Lisbon, , Portugal

Hospital Santa Maria

Lisbon, , Portugal

Hospital Pedro Hispano Matosinhos E P E

Matosinhos Municipality, , Portugal

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

Porto, , Portugal

MUDr Beata Dupejova s r o

Banská Bystrica, , Slovakia

Nemocnica sv Michala a s

Bratislava, , Slovakia

Nemocnica Komarno s r o

Komárno, , Slovakia

Neurologicke oddelenie VNsP Levoca

Levoča, , Slovakia

Neurolog odd NsP Liptovsky Mikulas

Liptovský Mikuláš, , Slovakia

Neurologicka a algeziologicka ambulancia SANERA s r o

Prešov, , Slovakia

Hospital Universitario Virgen del Rocio

Seville, Andalusia, Spain

Hospital Clinico Universitario de Valladolid

Valladolid, Castille and León, Spain

Hospital Vall D'Hebron

Barcelona, Catalonia, Spain

Hospital Clinico Universitario Valencia

Valencia, Communidad Valencia, Spain

Hospital Clinico Universitario de Santiago

Santiago de Compostela, Galicia, Spain

Hospital Quiron Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital La Paz

Madrid, , Spain

Hospital Marques de Valdecilla

Santander, , Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Queen Elizabeth Hospital Pharmacy Dept.

Edgbaston, Birmingham, United Kingdom

The John Radcliffe Hospital

Headington, Oxfordshire, United Kingdom

University Hospital of North Midlands NHS Trust

Stoke-on-Trent, Staffordshire, United Kingdom

Glasgow Clinical Research Facility

Glasgow, , United Kingdom

Hull and amp East Yorkshire Hospitals NHS Trust

Hull, , United Kingdom

St Thomas Hospital

London, , United Kingdom

King's College Hospital London

London, , United Kingdom

Royal Victoria Infirmary

Newcastile Upon Tyne, , United Kingdom

Salford Royal Hospital

Salford, , United Kingdom

Countries

United States; Argentina; Austria; Belgium; Czechia; Finland; France; Germany; Greece; Ireland; Israel; Italy; Netherlands; Poland; Portugal; Slovakia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38526461 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001228-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMG334A2401

Identifier Type: OTHER

Identifier Source: secondary_id

AMG334A2401

Identifier Type: -

Identifier Source: org_study_id