Study of Sustained Benefit of Erenumab in Adult Episodic Migraine Patients

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03927144

Collaborator

Novartis (Industry)

621

Enrollment

112

Locations

Arms

40.8

Anticipated Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate the superiority of subcutaneous erenumab compared to oral prophylactic(s) on sustained benefit defined as % subjects completing one-year on the randomized treatment and achieving at least a 50% reduction from baseline in monthly migraine days at month 12.

Condition or Disease	Intervention/Treatment	Phase
Episodic Migraine	Drug: Erenumab Drug: Oral Prophylactic	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

621 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 12-month Prospective, Randomized, Interventional, Global, Multi-center, Activecontrolled Study Comparing Sustained Benefit of Two Treatment Paradigms (Erenumab qm vs. Oral Prophylactics) in Adult Episodic Migraine Patients

Actual Study Start Date :

May 15, 2019

Actual Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Oct 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erenumab Escalate to Erenumab Dose 2 OR Switch to Oral Prophylactic during the first 52 weeks.	Drug: Erenumab Erenumab Dose 1 / Dose 2 Treatment Period up to 104 weeks Drug: Oral Prophylactic SoC oral prophylactic (active comparator) Treatment Period up to 52 weeks. Eligible treatment completers can roll over to post trial access open label treatment to receive 52 weeks of Erenumab Dose 1 / Dose 2.
Active Comparator: Oral Prophylactic Switch Oral Prophylactic during the first 52 weeks.	Drug: Oral Prophylactic SoC oral prophylactic (active comparator) Treatment Period up to 52 weeks. Eligible treatment completers can roll over to post trial access open label treatment to receive 52 weeks of Erenumab Dose 1 / Dose 2.

Arm

Intervention/Treatment

Experimental: Erenumab

Escalate to Erenumab Dose 2 OR Switch to Oral Prophylactic during the first 52 weeks.

Drug: Erenumab

Erenumab Dose 1 / Dose 2 Treatment Period up to 104 weeks

Drug: Oral Prophylactic

SoC oral prophylactic (active comparator) Treatment Period up to 52 weeks. Eligible treatment completers can roll over to post trial access open label treatment to receive 52 weeks of Erenumab Dose 1 / Dose 2.

Active Comparator: Oral Prophylactic

Switch Oral Prophylactic during the first 52 weeks.

Drug: Oral Prophylactic

Outcome Measures

Primary Outcome Measures

Proportion of subjects who complete initially assigned treatment and achieve at least 50% reduction from baseline in monthly migraine days at Month 12 [Month 12]
To demonstrate the superiority of subcutaneous erenumab compared to oral prophylactic(s) on sustained benefit defined as % subjects completing one-year on the randomized treatment and achieving at least a 50% reduction from baseline in monthly migraine days at month 12.

Secondary Outcome Measures

Proportion of subjects completing the treatment period at Month 12 on the initially assigned treatment [Month 12]
To evaluate the effect of erenumab compared to oral prophylactics on overall subject retention defined as % subjects completing treatment period at Month 12 on initially assigned treatment
Cumulative average change from baseline on the monthly migraine days during the treatment period for subjects on the initially assigned treatment (Months 1-12) [Month 12]
To evaluate the effect of erenumab compared to oral prophylactics on the change from baseline in monthly migraine days during the treatment period
Proportion of responders (PGI-I score greater than or equal to 5) as measured by PGIC at month 12 for subjects completing the treatment period at Month 12 on initially assigned treatment [Month 12]
To evaluate the effect of erenumab compared to oral prophylactics on the subject's assessment of the change in clinical status since the start of treatment as measured by the Patients' Global Impression of Change (PGIC) Scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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 erenumab or exposure to any other prophylactic CGRP-targeted therapy (prior to the study).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Headache Center	Stanford	California	United States	94305
2	Yale Center for Clinical Research	New Haven	Connecticut	United States	06519
3	New England Institute for Neurology and Headache	Stamford	Connecticut	United States	06905
4	George Washington Hospital	Washington	District of Columbia	United States	20037
5	University of Miami Headache Division	Miami	Florida	United States	33136
6	Premier Research Institute	West Palm Beach	Florida	United States	33407
7	Diamond Headache Clinic	Chicago	Illinois	United States	60642
8	Robbins Headache Clinic	Riverwoods	Illinois	United States	60015
9	Medvadis	Watertown	Massachusetts	United States	02472
10	New England Regional Headache Center, Inc	Worcester	Massachusetts	United States	01605
11	MHNI	Ann Arbor	Michigan	United States	48104
12	Clinical Research Institute	Minneapolis	Minnesota	United States	55402
13	The Headache Center	Ridgeland	Mississippi	United States	38157
14	Mercy Health Research	Saint Louis	Missouri	United States	63141
15	Study Metrix Research	Saint Peters	Missouri	United States	63303
16	Laszlo Mechtler	Amherst	New York	United States	14226
17	Jefferson Headache Center	Philadelphia	Pennsylvania	United States	19107
18	Nashville Neuroscience Group	Nashville	Tennessee	United States	37203
19	Texas Neurology	Dallas	Texas	United States	75214
20	Texas Institute for Neurological Disorders	Sherman	Texas	United States	75092
21	IDIM Instituto de Investigaciones Metabolicas	Buenos Aires		Argentina	C1012AAR
22	Mautalen Salud e Investigacion	Ciudad Autonoma de Bs As		Argentina	C1128AAF
23	Centro Medico Privado en Reumatologia	Tucuman		Argentina	4000
24	Univ. Klinik fuer Neurologie	Innsbruck		Austria	A 6020
25	Ordensklinikum Linz Barmherzigen Schwestern	Linz		Austria	4010
26	Univ Klinik fuer AKH	Vienna		Austria	1090
27	AZ Sint Jan	Brugge		Belgium	8000
28	UZ Brussel	Brussel		Belgium	1090
29	UZ Gent	Gent		Belgium	9000
30	Jessa Ziekenhuis- Campus Virga Jesse Dienst Gastro-entrologie	Hasselt		Belgium	3500
31	Centre Hospitalier Regional de la Citadelle	Liege		Belgium	4000
32	Heilig Hart Ziekenhuis Lier	Lier		Belgium	2500
33	Neurologicka ambulance Quattromedica	Brno		Czechia	602 00
34	NEUROHK sro	Chocen		Czechia	56501
35	Brain Soultherapy sro	Kladno		Czechia	272 01
36	DADO Medical S R O	Prague		Czechia	120 00
37	Institut neuropsychiatricke pece	Prague		Czechia	18600
38	Clintrial SRO	Praha 10		Czechia
39	Thomayerova Nemocnice	Praha 4		Czechia	140 59
40	Forbeli SRO	Praha 6		Czechia	160 00
41	Vestra Clinics sro	Rychnov nad Kneznou		Czechia	516 01
42	Terveystalo Ruoholahti	Helsinki		Finland	00180
43	Laakarikeskus Aava Itakeskus	Helsinki		Finland	00930
44	Terveystalo Pulssi	Turku		Finland	20100
45	CHRU de LILLE	LILLE Cedex		France	59037
46	Hopital Lariboisiere Centre d Urgence des Cephalees	Paris cedex 10		France	75010
47	Hopital Charles Nicolle Departement de Neurologie	Rouen		France	76031
48	CH Yves Le Foll	Saint Brieuc		France	22000
49	CHU St Etienne Hopital Nord Bat A	SAINT ETIENNE cedex 2		France	42055
50	GP Dept of Neurology	Bochum		Germany	D 44787
51	Neurologische Gemeinschaftspraxis Klemt & Bauersachs	Dortmund		Germany	44135
52	Neurologische Gemeinschaftpraxis im Bienenkorbhaus	Frankfurt		Germany	60313
53	AmBeNet Hausarztpraxis	Leipzig		Germany	04107
54	Medamed GmbH Studienambulanz	Leipzig		Germany	04109
55	Navy Hospital of Athens "NNA" Main Centre	Athens		Greece	115 21
56	Aeginition Hospital of Athens, University of Athens	Athens		Greece	115 28
57	Neurologicka Ambulancia Konzilium s r o	Athens		Greece	115 28
58	401 Army General Hospital of Athens Main Centre	Athens		Greece	11525
59	MEDITERRANEO Hospital	Glyfada		Greece	16675
60	General Hospital of Patra O AGIOS ANDREAS Neurology Clinic	Patra		Greece	26335
61	Euromedica General Clinic of Thessaloniki Neurology Dept	Thessaloniki		Greece	54645
62	Bon Secours Hospital	Cork		Ireland	T12 DV56
63	Beaumont Hospital	Dublin 9		Ireland	47735
64	Hillel Yaffe MC	Hadera		Israel	38100
65	Rambam Medical Center	Haifa		Israel	31096
66	Laniado	Netanya		Israel	42150
67	Sheba MC	Ramat Gan		Israel	52621
68	Tel Aviv Sourasky Medical Center Ichilov	Tel Aviv		Israel	64239
69	A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte	Perugia	PG	Italy	06129
70	IRCCS San Raffaele Pisana	Roma	RM	Italy	00163
71	Ospedali Riuniti Torrette di Ancona	Ancona		Italy	60126
72	ASST degli Spedali Civili di Brescia Univ degli Studi	Brescia		Italy	25100
73	Policl.Universit.Campus Bio-Medico Università Campus Bio-Med U.O.C.Area di Oncologia Medica	Roma		Italy	00128
74	Azienda Ospedaliera Sant'Andrea - Università La Sapienza	Roma		Italy	00189
75	Zuyderland Medisch Centrum	Geleen		Netherlands	6162 BG
76	Martini Ziekenhuis	Groningen		Netherlands	9728 NT
77	Canisius Wilhelmina Hospital Dept of Neurology C-70	Nijmegen		Netherlands	6532 NZ
78	Isala Ziekenhuis	Zwolle		Netherlands	8025AB
79	Centrum Leczenia Padaczki i Migreny	Krakow		Poland	31-209
80	Gabient Lekarski Jacek Rozniecki	Lodz		Poland	90 153
81	OHA MED Sp zo o	Warszawa		Poland	00 144
82	ETG Warszawa	Warszawa		Poland	02 777
83	Wojskowy Instutyt Medyczny CSK MON	Warszawa		Poland	04146
84	Hospital Garcia de Orta EPE	Almada		Portugal	2801 951
85	Hospital da Luz	Lisboa		Portugal	1500 650
86	Hospital Santa Maria	Lisboa		Portugal	1600190
87	Hospital Pedro Hispano Matosinhos E P E	Matosinhos		Portugal	4464-513
88	Centro Hospitalar do Porto Hospital Geral de Santo Antonio Serviço de Neurologia	Porto		Portugal	4099-001
89	MUDr Beata Dupejova s r o	Banska Bystrica		Slovakia	974 04
90	Nemocnica sv Michala a s	Bratislava		Slovakia	811 08
91	Nemocnica Komarno s r o	Komarno		Slovakia	945 75
92	Neurologicke oddelenie VNsP Levoca	Levoca		Slovakia	054 01
93	Neurolog odd NsP Liptovsky Mikulas	Liptovsky Mikulas		Slovakia	031 23
94	Neurologicka a algeziologicka ambulancia SANERA s r o	Presov		Slovakia	08001
95	Hospital Universitario Virgen del Rocio	Sevilla	Andalucia	Spain	41013
96	Hospital Clinico Universitario de Valladolid	Valladolid	Castilla Y Leon	Spain	47011
97	Hospital Vall D'Hebron	Barcelona	Cataluña	Spain	08035
98	Hospital Clinico Universitario Valencia	Valencia	Communidad Valencia	Spain	46010
99	Hospital Clinico Universitario de Santiago	Santiago de Compostela	Galicia	Spain	15706
100	Hospital Quiron Madrid	Pozuelo de Alarcon	Madrid	Spain	28223
101	Hospital La Paz	Madrid		Spain	28046
102	Hospital Marques de Valdecilla	Santander		Spain	39008
103	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
104	Queen Elizabeth Hospital Pharmacy Dept.	Edgbaston	Birmingham	United Kingdom	B15 2TH
105	The John Radcliffe Hospital	Headington	Oxfordshire	United Kingdom	OX3 9DU
106	University Hospital of North Midlands NHS Trust	Stoke on Trent	Staffordshire	United Kingdom	ST46QG
107	Glasgow Clinical Research Facility	Glasgow		United Kingdom	G51 4TF
108	Hull and amp East Yorkshire Hospitals NHS Trust	Hull		United Kingdom	HU3 2JZ
109	St Thomas Hospital	London		United Kingdom	SE1 7EH
110	King's College Hospital London	London		United Kingdom	SE5 9RS
111	Royal Victoria Infirmary	Newcastile Upon Tyne		United Kingdom	NE1 4LP
112	Salford Royal Hospital	Salford		United Kingdom	M6 8HD