Clinical trial NCT02456740: Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) 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
Prevention
Prophylaxis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-05-28
Enrollment: 955
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: The primary objective of the study was to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days.

Detailed description: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The trial consisted of four phases: screening (≤ 3 weeks of initial screening and a 4-week baseline phase); the double-blind treatment phase (24 weeks) in which participants received placebo or erenumab 70 mg or 140 mg daily; the active-treatment phase, in which participants underwent repeat randomization and were assigned to receive 70 mg or 140 mg of erenumab (28 weeks); and a safety follow-up phase (12 weeks).

Eligibility criteria: Inclusion Criteria:

* History of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-3) classification
* Migraine frequency: ≥ 4 and \< 15 migraine days per month on average across the 3 months prior to screening and during baseline
* Headache frequency: \< 15 headache days per month on average across the 3 months prior to screening and baseline
* Demonstrated at least 80% 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 headache
* No therapeutic response with \> 2 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial
* Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase
* 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

Primary outcomes:
measure: Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months of the Double-blind Treatment Period
timeFrame: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Secondary outcomes:
measure: Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase
timeFrame: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
measure: Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period
timeFrame: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
measure: Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase
timeFrame: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
measure: Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase
timeFrame: 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Encino
country: United States
facility: Research Site
state: California
city: Irvine
country: United States
facility: Research Site
state: California
city: Los Alamitos
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Rancho Mirage
country: United States
facility: Research Site
state: California
city: Redlands
country: United States
facility: Research Site
state: California
city: Sherman Oaks
country: United States
facility: Research Site
state: California
city: Simi Valley
country: United States
facility: Research Site
state: California
city: Spring Valley
country: United States
facility: Research Site
state: California
city: Boulder
country: United States
facility: Research Site
state: Colorado
city: East Hartford
country: United States
facility: Research Site
state: Connecticut
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Bradenton
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Leesburg
country: United States
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city: Miami
country: United States
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state: Florida
city: Ocala
country: United States
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city: Orlando
country: United States
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state: Florida
city: Sunrise
country: United States
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state: Florida
city: West Palm Beach
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Boise
country: United States
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state: Idaho
city: Evansville
country: United States
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state: Indiana
city: Des Moines
country: United States
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state: Iowa
city: Newton
country: United States
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state: Kansas
city: Wichita
country: United States
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state: Kansas
city: Edgewood
country: United States
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state: Kentucky
city: Metairie
country: United States
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state: Louisiana
city: New Orleans
country: United States
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state: Louisiana
city: New Bedford
country: United States
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state: Massachusetts
city: Worcester
country: United States
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state: Massachusetts
city: Plymouth
country: United States
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state: Minnesota
city: Kansas City
country: United States
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state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Springfield
country: United States
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state: Missouri
city: Amherst
country: United States
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state: New York
city: Plainview
country: United States
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state: New York
city: Rochester
country: United States
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state: New York
city: Durham
country: United States
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state: North Carolina
city: Greensboro
country: United States
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state: North Carolina
city: Cleveland
country: United States
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state: Ohio
city: Cleveland
country: United States
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state: Ohio
city: Willoughby Hills
country: United States
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state: Ohio
city: Portland
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state: Oregon
city: Philadelphia
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state: Pennsylvania
city: Cumberland
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state: Rhode Island
city: Port Royal
country: United States
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state: South Carolina
city: Memphis
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state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Austin
country: United States
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state: Texas
city: Bedford
country: United States
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state: Texas
city: Irving
country: United States
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state: Texas
city: San Antonio
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state: Texas
city: Salt Lake City
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state: Utah
city: West Jordan
country: United States
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state: Utah
city: Charlottesville
country: United States
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state: Virginia
city: Innsbruck
country: Austria
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Brussel
country: Belgium
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city: Gent
country: Belgium
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city: Hasselt
country: Belgium
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city: Liege
country: Belgium
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city: Lodelinsart
country: Belgium
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city: Surrey
country: Canada
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state: British Columbia
city: Hamilton
country: Canada
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state: Ontario
city: Markham
country: Canada
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state: Ontario
city: Ottawa
country: Canada
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state: Ontario
city: Levis
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Kuopio
country: Finland
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Turku
country: Finland
facility: Research Site
city: Berlin (Hellersdorf)
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hüttenberg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Swidnik
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Komarno
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Falköping
country: Sweden
facility: Research Site
city: Helsingborg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uddevalla
country: Sweden
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Sidcup
country: United Kingdom
facility: Research Site
city: Stoke on Trent
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Buse DC, Lipton RB, Hallstrom Y, Reuter U, Tepper SJ, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab. Cephalalgia. 2018 Sep;38(10):1622-1631. doi: 10.1177/0333102418789072. Epub 2018 Aug 7.
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: Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.
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citation: McAllister PJ, Turner I, Reuter U, Wang A, Scanlon J, Klatt J, Chou DE, Paiva da Silva Lima G. Timing and durability of response to erenumab in patients with episodic migraine. Headache. 2021 Nov;61(10):1553-1561. doi: 10.1111/head.14233. Epub 2021 Nov 28.
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: Lipton RB, Dodick DW, Kudrow D, Reuter U, Tenenbaum N, Zhang F, Lima GPDS, Chou DE, Mikol DD. Reduction in migraine pain intensity in patients treated with erenumab: A post hoc analysis of two pivotal randomized studies. Cephalalgia. 2021 Dec;41(14):1458-1466. doi: 10.1177/03331024211028966. Epub 2021 Aug 18.
citation: Yucel A, Thach A, Kumar S, Loden C, Bensink M, Goldfarb N. Estimating the economic burden of migraine on US employers. Am J Manag Care. 2020 Dec 1;26(12):e403-e408. doi: 10.37765/ajmc.2020.88547.
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.
citation: Tepper SJ, Ashina M, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Picard H, Cheng S, Chou DE, Zhang F, Klatt J, Mikol DD. Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials. J Headache Pain. 2021 Jul 23;22(1):81. doi: 10.1186/s10194-021-01292-w.
citation: Diener HC, Ashina M, Ritter S, Paiva Da Silva Lima G, Rasmussen S, Zielman R, Tfelt-Hansen P. Erenumab prevents the occurrence of migraine attacks and not just migraine days: Post-hoc analyses of a phase III study. Cephalalgia. 2021 Oct;41(11-12):1262-1267. doi: 10.1177/03331024211010308. Epub 2021 May 3.
citation: Broessner G, Reuter U, Bonner JH, Dodick DW, Hallstrom Y, Picard H, Zhang F, Lenz RA, Klatt J, Mikol DD. The Spectrum of Response to Erenumab in Patients With Episodic Migraine and Subgroup Analysis of Patients Achieving >/=50%, >/=75%, and 100% Response. Headache. 2020 Oct;60(9):2026-2040. doi: 10.1111/head.13929. Epub 2020 Aug 26.
citation: Pavlovic JM, Paemeleire K, Gobel H, Bonner J, Rapoport A, Kagan R, Zhang F, Picard H, Mikol DD. Efficacy and safety of erenumab in women with a history of menstrual migraine. J Headache Pain. 2020 Aug 3;21(1):95. doi: 10.1186/s10194-020-01167-6.
citation: Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Wright IK, Chou DE, Klatt J, Picard H, Lenz RA, Mikol DD. One-year sustained efficacy of erenumab in episodic migraine: Results of the STRIVE study. Neurology. 2020 Aug 4;95(5):e469-e479. doi: 10.1212/WNL.0000000000010019. Epub 2020 Jul 7.