Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention

Migraine Clinical Trial

— ARISE  

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02483585
• Other study ID #: 20120297
• Secondary ID: 2014-004463-20
• Status: Completed
• Phase: Phase 3
• Start date: July 20, 2015
• Est. completion date: March 20, 2017

Study information

• Verified date: October 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days, in adults with episodic migraine.

Description:

Adults with a history of migraine with or without aura for ≥ 12 months and who experience ≥ 4 to < 15 migraine days per month with < 15 headache days per month will be randomized 1:1 to placebo or erenumab. Double-blind erenumab or placebo will be administered during the 12-week double-blind treatment phase and open-label erenumab will be administered during the 28-week open-label treatment phase.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 577
• Est. completion date: March 20, 2017
• Est. primary completion date: July 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• History of migraines (with or without aura) for = 12 months
• Migraine frequency: = 4 and < 15 migraine days per month on average acrossthe 3 months prior to screening
• Headache (ie, migraine and non-migraine headache) frequency: < 15 headache days per month on average across the 3 months prior to screening
• Demonstrated compliance with the eDiary

Exclusion Criteria:

• Older than 50 years of age at migraine onset.
• History of cluster headache or hemiplegic migraine headache.
• Unable to differentiate migraine from other headaches
• No therapeutic response with > 2 categories for prophylactic treatment of migraine after an adequate therapeutic trial.
• Concomitant use of 2 or more medications with possible migraine prophylactic effects within 2 months prior to the start of the baseline phase or during the baseline phase. If only 1 prophylactic medication is used, the dose must be stable within 2 months prior to the start of the baseline phase and throughout the study
• Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase.
• Received botulinum toxin
• Anticipated to require any excluded medication, device, or procedure during the study.
• Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain).
• History of major psychiatric disorder.
• History of seizure disorder or other significant neurological conditions other than migraine.
• Human immunodeficiency virus (HIV) infection by history.
• Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening.
• The subject is at risk of self-harm or harm to others. Previously randomized into an AMG 334 study.
• Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Administered once a month by subcutaneous injection
• Placebo
Administered once a month by subcutaneous injection

Locations

Country	Name	City	State
Denmark	Research Site	Aalborg
Denmark	Research Site	Ballerup
Denmark	Research Site	Glostrup
Denmark	Research Site	Vejle
France	Research Site	Bordeaux Cedex
France	Research Site	Nice cedex 1
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Pringy Cedex
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Portugal	Research Site	Amadora
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Torres Vedras
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Ufa
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Madrid
Spain	Research Site	Santander	Cantabria
Spain	Research Site	Santiago de Compostela	Galicia
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valencia	Comunidad Valenciana
Spain	Research Site	Valladolid	Castilla León
Spain	Research Site	Zaragoza	Aragón
Switzerland	Research Site	Bad Zurzach
Switzerland	Research Site	Biel
Switzerland	Research Site	Geneve
Switzerland	Research Site	Lugano
Switzerland	Research Site	St Gallen
Switzerland	Research Site	Zollikon
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Asheville	North Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Culver City	California
United States	Research Site	Dallas	Texas
United States	Research Site	Fairfield	Connecticut
United States	Research Site	Gurnee	Illinois
United States	Research Site	Hollywood	Florida
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Lenexa	Kansas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Long Beach	California
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Oviedo	Florida
United States	Research Site	Palm Beach Gardens	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Princeton	New Jersey
United States	Research Site	Sacramento	California
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Diego	California
United States	Research Site	Santa Monica	California
United States	Research Site	Seattle	Washington
United States	Research Site	Virginia Beach	Virginia
United States	Research Site	Walnut Creek	California
United States	Research Site	Warwick	Rhode Island
United States	Research Site	Williamsville	New York
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Denmark,  France,  Greece,  Portugal,  Russian Federation,  Spain,  Switzerland, 

References & Publications (6)

Ashina M, Kudrow D, Reuter U, Dolezil D, Silberstein S, Tepper SJ, Xue F, Picard H, Zhang F, Wang A, Zhou Y, Hong F, Klatt J, Mikol DD. Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions. Cephalalgia. 2019 Dec;39(14):1798-1808. doi: 10.1177/0333102419888222. Epub 2019 Nov 10. — View Citation

Cheng S, Picard H, Zhang F, Eisele O, Mikol DD. Efficacy and safety of erenumab for migraine prevention: an overview. Japanese Journal of Headache. 2019; 45 : 493-505.

Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018 May;38(6):1026-1037. doi: 10.1177/0333102418759786. Epub 2018 Feb 22. — View Citation

Kawata AK, Ladd MK, Lipton RB, Buse DC, Bensink M, Shah S, Hareendran A, Mannix S, Mikol D. Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials. Headache. 2022 Feb;62(2):159-168. doi: 10.1111/head.14258. Epub 2022 Feb 8. — View Citation

Kudrow D, Pascual J, Winner PK, Dodick DW, Tepper SJ, Reuter U, Hong F, Klatt J, Zhang F, Cheng S, Picard H, Eisele O, Wang J, Latham JN, Mikol DD. Vascular safety of erenumab for migraine prevention. Neurology. 2020 Feb 4;94(5):e497-e510. doi: 10.1212/WNL.0000000000008743. Epub 2019 Dec 18. Erratum in: Neurology. 2020 Jun 9;94(23):1052. — View Citation

Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Monthly Migraine Days at Week 12	A migraine day was 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 either as a migraine with or without aura.; The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary	Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12	A migraine day was 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 either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of double-blind treatment.; At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 4 weeks of the 12-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary	Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days at Week 12	Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.; The change from baseline in monthly acute migraine-specific treatment days was calculated as the number of migraine-specific treatment days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine-specific treatment days during the 4-week baseline phase.	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary	Percentage of Participants With at Least a 5-point Reduction From Baseline in Average Impact on Everyday Activities Domain Score Measured by MPFID at Week 12	The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.; Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was = -5.	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary	Percentage of Participants With at Least a 5-Point Reduction From Baseline in Average Impact on Physical Impairment Domain Score Measured by MPFID at Week 12	The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.; Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was = -5.	4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary	Number of Participants With Adverse Events	Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.	From first dose of study drug up to 12 weeks after the last dose. The double-blind treatment phase was 12 weeks and the open-label treatment phase was 28 weeks.
Secondary	Number of Participants Who Developed Antibodies to Erenumab	Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay).; Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline.; If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.; Transient indicates a negative result at the participant's last time point tested, for those participants with a positive binding/neutralizing result post-baseline.	Baseline (the period prior to the first dose erenumab 70 mg) and post-baseline (the period after the first dose of erenumab 70 mg until 12 weeks after last dose, up to 48 weeks total)

External Links

•   AmgenTrials clinical trials website