Clinical trial NCT02483585: Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Keywords: Migraine
Headache
Episodic
Prevention
Prophylaxis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-06-29
Enrollment: 577
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Monthly Migraine Days at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Secondary outcomes:
measure: Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: 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
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: 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
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: Number of Participants With Adverse Events
timeFrame: 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.
measure: Number of Participants Who Developed Antibodies to Erenumab
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Culver City
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Fairfield
country: United States
facility: Research Site
state: Connecticut
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Oviedo
country: United States
facility: Research Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Gurnee
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Lenexa
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Princeton
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Williamsville
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Warwick
country: United States
facility: Research Site
state: Rhode Island
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Virginia Beach
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Aalborg
country: Denmark
facility: Research Site
city: Ballerup
country: Denmark
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Nice cedex 1
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pringy Cedex
country: France
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Amadora
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Torres Vedras
country: Portugal
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
state: Aragón
city: Santander
country: Spain
facility: Research Site
state: Cantabria
city: Valladolid
country: Spain
facility: Research Site
state: Castilla León
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Research Site
state: Galicia
city: Madrid
country: Spain
facility: Research Site
city: Bad Zurzach
country: Switzerland
facility: Research Site
city: Biel
country: Switzerland
facility: Research Site
city: Geneve
country: Switzerland
facility: Research Site
city: Lugano
country: Switzerland
facility: Research Site
city: St Gallen
country: Switzerland
facility: Research Site
city: Zollikon
country: Switzerland
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
citation: 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.
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.
citation: Lampl C, Kraus V, Lehner K, Loop B, Chehrenama M, Maczynska Z, Ritter S, Klatt J, Snellman J. Safety and tolerability of erenumab in individuals with episodic or chronic migraine across age groups: a pooled analysis of placebo-controlled trials. J Headache Pain. 2022 Aug 18;23(1):104. doi: 10.1186/s10194-022-01470-4.
citation: Ashina M, Goadsby PJ, Dodick DW, Tepper SJ, Xue F, Zhang F, Brennan F, Paiva da Silva Lima G. Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials. JAMA Neurol. 2022 Feb 1;79(2):159-168. doi: 10.1001/jamaneurol.2021.4678.