Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

Episodic Migraine Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03927144
• Other study ID #: AMG334A2401
• Secondary ID: 2018-001228-20CA
• Status: Completed
• Phase: Phase 4
• Start date: May 15, 2019
• Est. completion date: September 30, 2022

Study information

• Verified date: October 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 621
• Est. completion date: September 30, 2022
• Est. primary completion date: October 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Episodic Migraine
• Migraine Disorders

Intervention

Drug:
• AMG334
Subcutaneous Injection
• Oral Prophylactic
SOC Oral Tablet/Capsule

Locations

Country	Name	City	State
Argentina	IDIM Instituto de Investigaciones Metabolicas	Buenos Aires
Argentina	Mautalen Salud e Investigacion	Ciudad Autonoma de Bs As
Argentina	Centro Medico Privado en Reumatologia	Tucuman
Austria	Univ. Klinik fuer Neurologie	Innsbruck
Austria	Ordensklinikum Linz Barmherzigen Schwestern	Linz
Austria	Univ Klinik fuer AKH	Vienna
Belgium	AZ Sint Jan	Brugge
Belgium	UZ Brussel	Brussel
Belgium	UZ Gent	Gent
Belgium	Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie	Hasselt
Belgium	Centre Hospitalier Regional de la Citadelle	Liege
Belgium	Heilig Hart Ziekenhuis Lier	Lier
Czechia	Neurologicka ambulance Quattromedica	Brno
Czechia	NEUROHK sro	Chocen
Czechia	Brain Soultherapy sro	Kladno
Czechia	DADO Medical S R O	Prague
Czechia	Institut neuropsychiatricke pece	Prague
Czechia	Clintrial SRO	Praha 10
Czechia	Thomayerova Nemocnice	Praha 4
Czechia	Forbeli SRO	Praha 6
Czechia	Vestra Clinics sro	Rychnov nad Kneznou
Finland	Laakarikeskus Aava Itakeskus	Helsinki
Finland	Terveystalo Ruoholahti	Helsinki
Finland	Terveystalo Pulssi	Turku
France	CHRU de LILLE	LILLE Cedex
France	Hopital Lariboisiere Centre d Urgence des Cephalees	Paris cedex 10
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 cedex 2
Germany	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
Greece	401 Army General Hospital of Athens Main Centre	Athens
Greece	Aeginition Hospital of Athens, University of Athens	Athens
Greece	Navy Hospital of Athens "NNA" Main Centre	Athens
Greece	Neurologicka Ambulancia Konzilium s r o	Athens
Greece	MEDITERRANEO Hospital	Glyfada
Greece	General Hospital of Patra O AGIOS ANDREAS Neurology Clinic	Patra
Greece	Euromedica General Clinic of Thessaloniki Neurology Dept	Thessaloniki
Ireland	Bon Secours Hospital	Cork
Ireland	Beaumont Hospital	Dublin 9
Israel	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
Italy	Ospedali Riuniti Torrette di Ancona	Ancona
Italy	ASST degli Spedali Civili di Brescia Univ degli Studi	Brescia
Italy	A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte	Perugia	PG
Italy	Azienda Ospedaliera Sant'Andrea - Università La Sapienza	Roma
Italy	IRCCS San Raffaele Pisana	Roma	RM
Italy	Policl.Universit.Campus Bio-Medico Università Campus Bio-Med U.O.C.Area di Oncologia Medica	Roma
Netherlands	Zuyderland Medisch Centrum	Geleen
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Canisius Wilhelmina Hospital Dept of Neurology C-70	Nijmegen
Netherlands	Isala Ziekenhuis	Zwolle
Poland	Centrum Leczenia Padaczki i Migreny	Krakow
Poland	Gabient Lekarski Jacek Rozniecki	Lodz
Poland	ETG Warszawa	Warszawa
Poland	OHA MED Sp zo o	Warszawa
Poland	Wojskowy Instutyt Medyczny CSK MON	Warszawa
Portugal	Hospital Garcia de Orta EPE	Almada
Portugal	Hospital da Luz	Lisboa
Portugal	Hospital Santa Maria	Lisboa
Portugal	Hospital Pedro Hispano Matosinhos E P E	Matosinhos
Portugal	Centro Hospitalar do Porto Hospital Geral de Santo Antonio Serviço de Neurologia	Porto
Slovakia	MUDr Beata Dupejova s r o	Banska Bystrica
Slovakia	Nemocnica sv Michala a s	Bratislava
Slovakia	Nemocnica Komarno s r o	Komarno
Slovakia	Neurologicke oddelenie VNsP Levoca	Levoca
Slovakia	Neurolog odd NsP Liptovsky Mikulas	Liptovsky Mikulas
Slovakia	Neurologicka a algeziologicka ambulancia SANERA s r o	Presov
Spain	Hospital Vall D'Hebron	Barcelona	Cataluña
Spain	Hospital La Paz	Madrid
Spain	Hospital Quiron Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	Galicia
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucia
Spain	Hospital Clinico Universitario Valencia	Valencia	Communidad Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid	Castilla Y Leon
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
United Kingdom	Queen Elizabeth Hospital Pharmacy Dept.	Edgbaston	Birmingham
United Kingdom	Glasgow Clinical Research Facility	Glasgow
United Kingdom	The John Radcliffe Hospital	Headington	Oxfordshire
United Kingdom	Hull and amp East Yorkshire Hospitals NHS Trust	Hull
United Kingdom	King's College Hospital London	London
United Kingdom	St Thomas Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastile Upon Tyne
United Kingdom	Salford Royal Hospital	Salford
United Kingdom	University Hospital of North Midlands NHS Trust	Stoke on Trent	Staffordshire
United States	Laszlo Mechtler	Amherst	New York
United States	MHNI	Ann Arbor	Michigan
United States	Diamond Headache Clinic	Chicago	Illinois
United States	Texas Neurology	Dallas	Texas
United States	University of Miami Headache Division	Miami	Florida
United States	Clinical Research Institute	Minneapolis	Minnesota
United States	Nashville Neuroscience Group	Nashville	Tennessee
United States	Yale Center for Clinical Research	New Haven	Connecticut
United States	Jefferson Headache Center	Philadelphia	Pennsylvania
United States	The Headache Center	Ridgeland	Mississippi
United States	Robbins Headache Clinic	Riverwoods	Illinois
United States	Mercy Health Research	Saint Louis	Missouri
United States	Study Metrix Research	Saint Peters	Missouri
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	New England Institute for Neurology and Headache	Stamford	Connecticut
United States	Stanford Headache Center	Stanford	California
United States	George Washington Hospital	Washington	District of Columbia
United States	Medvadis	Watertown	Massachusetts
United States	Premier Research Institute	West Palm Beach	Florida
United States	New England Regional Headache Center, Inc	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Novartis

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: Unilateral; Throbbing; Moderate to severe; Exacerbated with exercise/physical activity; =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	Number of Participants Who Completed Initially Assigned Treatment at Month 12		Month 12
Secondary	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
Secondary	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