Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

NCT03927144 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: AMG334A24012018-001228-20CAMG334A2401
• Study Type: interventional
• Target: 621
• Locations: 18 countries
• Sites: 112

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

Keywords

Erenumab; AMG334; Migraine; Episodic; Headache; CGRP

Outcome Measures

Primary Outcomes (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 2. ≥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.

  Baseline and Month 12

Secondary Outcomes (3)

• 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

  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

  Baseline and Week 52

Study Arms (2)

AMG334 70 mg/140 mg

EXPERIMENTAL

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; Drug: Oral Prophylactic

Oral Prophylactic

ACTIVE COMPARATOR

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; Drug: Oral Prophylactic

Interventions

AMG334 DRUG

Subcutaneous Injection

Also known as: Erenumab

AMG334 70 mg/140 mg; Oral Prophylactic

Oral Prophylactic DRUG

SOC Oral Tablet/Capsule

AMG334 70 mg/140 mg; Oral Prophylactic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead
• Novartis: collaborator

Study Sites (112)

Stanford Headache Center

Stanford, California, 94305, United States

Location

Yale Center for Clinical Research

New Haven, Connecticut, 06519, United States

Location

New England Institute for Neurology and Headache

Stamford, Connecticut, 06905, United States

Location

George Washington Hospital

Washington D.C., District of Columbia, 20037, United States

Location

University of Miami Headache Division

Miami, Florida, 33136, United States

Location

Premier Research Institute

West Palm Beach, Florida, 33407, United States

Location

Diamond Headache Clinic

Chicago, Illinois, 60642, United States

Location

Robbins Headache Clinic

Riverwoods, Illinois, 60015, United States

Location

Medvadis

Watertown, Massachusetts, 02472, United States

Location

New England Regional Headache Center, Inc

Worcester, Massachusetts, 01605, United States

Location

MHNI

Ann Arbor, Michigan, 48104, United States

Location

Clinical Research Institute

Minneapolis, Minnesota, 55402, United States

Location

The Headache Center

Ridgeland, Mississippi, 38157, United States

Location

Study Metrix Research

City of Saint Peters, Missouri, 63303, United States

Location

Mercy Health Research

St Louis, Missouri, 63141, United States

Location

Laszlo Mechtler

Amherst, New York, 14226, United States

Location

Jefferson Headache Center

Philadelphia, Pennsylvania, 19107, United States

Location

Nashville Neuroscience Group

Nashville, Tennessee, 37203, United States

Location

Texas Neurology

Dallas, Texas, 75214, United States

Location

Texas Institute for Neurological Disorders

Sherman, Texas, 75092, United States

Location

IDIM Instituto de Investigaciones Metabolicas

Buenos Aires, C1012AAR, Argentina

Location

Mautalen Salud e Investigacion

Ciudad Autonoma de Bs As, C1128AAF, Argentina

Location

Centro Medico Privado en Reumatologia

San Miguel de Tucumán, 4000, Argentina

Location

Univ. Klinik fuer Neurologie

Innsbruck, A 6020, Austria

Location

Ordensklinikum Linz Barmherzigen Schwestern

Linz, 4010, Austria

Location

Univ Klinik fuer AKH

Vienna, 1090, Austria

Location

AZ Sint Jan

Bruges, 8000, Belgium

Location

UZ Brussel

Brussels, 1090, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie

Hasselt, 3500, Belgium

Location

Heilig Hart Ziekenhuis Lier

Lier, 2500, Belgium

Location

Centre Hospitalier Regional de la Citadelle

Liège, 4000, Belgium

Location

Neurologicka ambulance Quattromedica

Brno, 602 00, Czechia

Location

NEUROHK sro

Choceň, 56501, Czechia

Location

Brain Soultherapy sro

Kladno, 272 01, Czechia

Location

DADO Medical S R O

Prague, 120 00, Czechia

Location

Thomayerova Nemocnice

Prague, 140 59, Czechia

Location

Forbeli SRO

Prague, 160 00, Czechia

Location

Institut neuropsychiatricke pece

Prague, 18600, Czechia

Location

Clintrial SRO

Prague, Czechia

Location

Vestra Clinics sro

Rychnov nad Kněžnou, 516 01, Czechia

Location

Terveystalo Ruoholahti

Helsinki, 00180, Finland

Location

Laakarikeskus Aava Itakeskus

Helsinki, 00930, Finland

Location

Terveystalo Pulssi

Turku, 20100, Finland

Location

CHRU de LILLE

Lille, 59037, France

Location

Hopital Lariboisiere Centre d Urgence des Cephalees

Paris, 75010, France

Location

Hopital Charles Nicolle Departement de Neurologie

Rouen, 76031, France

Location

CH Yves Le Foll

Saint-Brieuc, 22000, France

Location

CHU St Etienne Hopital Nord Bat A

Saint-Etienne, 42055, France

Location

GP Dept of Neurology

Bochum, D 44787, Germany

Location

Neurologische Gemeinschaftspraxis Klemt & Bauersachs

Dortmund, 44135, Germany

Location

Neurologische Gemeinschaftpraxis im Bienenkorbhaus

Frankfurt, 60313, Germany

Location

AmBeNet Hausarztpraxis

Leipzig, 04107, Germany

Location

Medamed GmbH Studienambulanz

Leipzig, 04109, Germany

Location

Navy Hospital of Athens "NNA" Main Centre

Athens, 115 21, Greece

Location

Aeginition Hospital of Athens, University of Athens

Athens, 115 28, Greece

Location

Neurologicka Ambulancia Konzilium s r o

Athens, 115 28, Greece

Location

401 Army General Hospital of Athens Main Centre

Athens, 11525, Greece

Location

MEDITERRANEO Hospital

Glyfada, 16675, Greece

Location

General Hospital of Patra O AGIOS ANDREAS Neurology Clinic

Pátrai, 26335, Greece

Location

Euromedica General Clinic of Thessaloniki Neurology Dept

Thessaloniki, 54645, Greece

Location

Bon Secours Hospital

Cork, T12 DV56, Ireland

Location

Beaumont Hospital

Dublin, 47735, Ireland

Location

Hillel Yaffe MC

Hadera, 38100, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Laniado

Netanya, 42150, Israel

Location

Sheba MC

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center Ichilov

Tel Aviv, 64239, Israel

Location

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

Perugia, PG, 06129, Italy

Location

IRCCS San Raffaele Pisana

Roma, RM, 00163, Italy

Location

Ospedali Riuniti Torrette di Ancona

Ancona, 60126, Italy

Location

ASST degli Spedali Civili di Brescia Univ degli Studi

Brescia, 25100, Italy

Location

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

Roma, 00128, Italy

Location

Azienda Ospedaliera Sant'Andrea - Università La Sapienza

Roma, 00189, Italy

Location

Zuyderland Medisch Centrum

Geleen, 6162 BG, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Canisius Wilhelmina Hospital Dept of Neurology C-70

Nijmegen, 6532 NZ, Netherlands

Location

Isala Ziekenhuis

Zwolle, 8025AB, Netherlands

Location

Centrum Leczenia Padaczki i Migreny

Krakow, 31-209, Poland

Location

Gabient Lekarski Jacek Rozniecki

Lodz, 90 153, Poland

Location

OHA MED Sp zo o

Warsaw, 00 144, Poland

Location

ETG Warszawa

Warsaw, 02 777, Poland

Location

Wojskowy Instutyt Medyczny CSK MON

Warsaw, 04146, Poland

Location

Hospital Garcia de Orta EPE

Almada, 2801 951, Portugal

Location

Hospital da Luz

Lisbon, 1500 650, Portugal

Location

Hospital Santa Maria

Lisbon, 1600190, Portugal

Location

Hospital Pedro Hispano Matosinhos E P E

Matosinhos Municipality, 4464-513, Portugal

Location

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

Porto, 4099-001, Portugal

Location

MUDr Beata Dupejova s r o

Banská Bystrica, 974 04, Slovakia

Location

Nemocnica sv Michala a s

Bratislava, 811 08, Slovakia

Location

Nemocnica Komarno s r o

Komárno, 945 75, Slovakia

Location

Neurologicke oddelenie VNsP Levoca

Levoča, 054 01, Slovakia

Location

Neurolog odd NsP Liptovsky Mikulas

Liptovský Mikuláš, 031 23, Slovakia

Location

Neurologicka a algeziologicka ambulancia SANERA s r o

Prešov, 08001, Slovakia

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Hospital Clinico Universitario de Valladolid

Valladolid, Castille and León, 47011, Spain

Location

Hospital Vall D'Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinico Universitario Valencia

Valencia, Communidad Valencia, 46010, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, Galicia, 15706, Spain

Location

Hospital Quiron Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Hospital Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Queen Elizabeth Hospital Pharmacy Dept.

Edgbaston, Birmingham, B15 2TH, United Kingdom

Location

The John Radcliffe Hospital

Headington, Oxfordshire, OX3 9DU, United Kingdom

Location

University Hospital of North Midlands NHS Trust

Stoke-on-Trent, Staffordshire, ST46QG, United Kingdom

Location

Glasgow Clinical Research Facility

Glasgow, G51 4TF, United Kingdom

Location

Hull and amp East Yorkshire Hospitals NHS Trust

Hull, HU3 2JZ, United Kingdom

Location

St Thomas Hospital

London, SE1 7EH, United Kingdom

Location

King's College Hospital London

London, SE5 9RS, United Kingdom

Location

Royal Victoria Infirmary

Newcastile Upon Tyne, NE1 4LP, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38526461 DERIVED

MeSH Terms

Conditions

Migraine Disorders; Recurrence; Headache

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 25, 2019
• Study Start: May 15, 2019
• Primary Completion: October 1, 2021
• Study Completion: September 30, 2022
• Last Updated: November 18, 2023
• Results First Posted: October 25, 2022

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6); SL (6); NL (4); PL (5); FI (3); DE (5); IE (2); PT (5); BE (6); IL (5); GB (9); GR (7); US (20); AR (3); ES (9); AU (3); CZ (9); FR (5)