Clinical trial NCT02066415: A Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Chronic Migraine Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Treatment for Prevention of Chronic Migraine
Keywords: Chronic Migraine
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2014-02-19
Enrollment: 667
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: PREVENTION

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

Detailed description: This study consisted of the following phases: screening, 4-week baseline phase, 12-week double-blind treatment, and 12-week follow-up. Participants may have elected to participate in the optional pharmacokinetic substudy and the optional, novel patient-reported outcome (PRO) assessment substudy.

Participants who completed the 12-week double-blind treatment phase of Study 20120295 were eligible to enroll in an open-label extension study (Study 20130255; NCT02174861).

Eligibility criteria: Inclusion Criteria:

* History of at least 5 attacks of migraine without aura and/or migraine with visual sensory, speech and/or language, retinal or brainstem aura.
* History of ≥ 15 headache days per month of which ≥ 8 headache days were assessed by the subject as migraine day.
* ≥ 4 distinct headache episodes, each lasting ≥ 4 hours OR if shorter, associated with use of a triptan or ergot-derivative on the same calendar day based on the eDiary calculations.
* Demonstrated at least 80% compliance with the eDiary.

Exclusion Criteria:

* History of cluster headache or hemiplegic migraine headache
* Unable to differentiate migraine from other headaches
* Failed \> 3 medication categories due to lack of efficacy for prophylactic treatment of migraine .
* Received botulinum toxinin head or neck region within 4 months prior to screening.
* Used a prohibited migraine prophylactic medication, device or procedure within 2 months prior to the start of the baseline phase

Primary outcomes:
measure: Change From Baseline in Monthly Migraine Days
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase
Secondary outcomes:
measure: Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Baseline
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase
measure: Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase
measure: Change From Baseline in Cumulative Monthly Headache Hours
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week treatment phase
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug up to 16 weeks after the last dose (24 weeks)
measure: Number of Participants Who Developed Antibodies to Erenumab
timeFrame: Baseline and weeks 2, 4, 8, 12 and 24
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Sherman Oaks
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Pikesville
country: United States
facility: Research Site
state: Maryland
city: Watertown
country: United States
facility: Research Site
state: Massachusetts
city: Worcester
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: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Springfield
country: United States
facility: Research Site
state: Missouri
city: Reno
country: United States
facility: Research Site
state: Nevada
city: Amherst
country: United States
facility: Research Site
state: New York
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
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: Dallas
country: United States
facility: Research Site
state: Texas
city: Temple
country: United States
facility: Research Site
state: Texas
city: Virginia Beach
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Jyväskylä
country: Finland
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Turku
country: Finland
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: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Königstein im Taunus
country: Germany
facility: Research Site
city: Lillehammar
country: Norway
facility: Research Site
city: Sandvika
country: Norway
facility: Research Site
city: Stavanger
country: Norway
facility: Research Site
city: Ålesund
country: Norway
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: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Falköping
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Vällingby
country: Sweden
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: London
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: Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun;16(6):425-434. doi: 10.1016/S1474-4422(17)30083-2. Epub 2017 Apr 28.
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: 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, Burstein R, Buse DC, Dodick DW, Koukakis R, Klatt J, Cheng S, Chou DE. Efficacy of erenumab in chronic migraine patients with and without ictal allodynia. Cephalalgia. 2021 Oct;41(11-12):1152-1160. doi: 10.1177/03331024211010305. Epub 2021 May 13.
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: Lipton RB, Tepper SJ, Reuter U, Silberstein S, Stewart WF, Nilsen J, Leonardi DK, Desai P, Cheng S, Mikol DD, Lenz R. Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study. Neurology. 2019 May 7;92(19):e2250-e2260. doi: 10.1212/WNL.0000000000007452. Epub 2019 Apr 17.
citation: Lipton RB, Tepper SJ, Silberstein SD, Kudrow D, Ashina M, Reuter U, Dodick DW, Zhang F, Rippon GA, Cheng S, Mikol DD. Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia. 2021 Jan;41(1):6-16. doi: 10.1177/0333102420973994. Epub 2020 Dec 3.
citation: Tepper SJ, Diener HC, Ashina M, Brandes JL, Friedman DI, Reuter U, Cheng S, Nilsen J, Leonardi DK, Lenz RA, Mikol DD. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology. 2019 May 14;92(20):e2309-e2320. doi: 10.1212/WNL.0000000000007497. Epub 2019 Apr 17.
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: Brandes JL, Diener HC, Dolezil D, Freeman MC, McAllister PJ, Winner P, Klatt J, Cheng S, Zhang F, Wen S, Ritter S, Lenz RA, Mikol DD. The spectrum of response to erenumab in patients with chronic migraine and subgroup analysis of patients achieving >/=50%, >/=75%, and 100% response. Cephalalgia. 2020 Jan;40(1):28-38. doi: 10.1177/0333102419894559. Epub 2019 Dec 9.