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

NCT02483585 | Completed Phase 3 Results DMC

• 2 other identifiers: 201202972014-004463-20
• Study Type: interventional
• Target: 577
• Locations: 8 countries
• Sites: 76

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.

Conditions

Migraine

Keywords

Migraine; Headache; Episodic; Prevention; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days at Week 12

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• 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

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• 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

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• Number of Participants With Adverse Events

  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.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. At week 12 participants began treatment with erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase.

Drug: Placebo

Erenumab

EXPERIMENTAL

Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants continued to receive erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase.

Drug: Erenumab

Interventions

Erenumab DRUG

Administered once a month by subcutaneous injection

Also known as: AMG 334, Aimovig™

Erenumab

Placebo DRUG

Administered once a month by subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (76)

Research Site

Birmingham, Alabama, 35216, United States

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Phoenix, Arizona, 85018, United States

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Culver City, California, 90230, United States

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Long Beach, California, 90806, United States

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Sacramento, California, 95821, United States

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San Diego, California, 92103, United States

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Santa Monica, California, 90404, United States

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Walnut Creek, California, 94598, United States

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Colorado Springs, Colorado, 80907, United States

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Fairfield, Connecticut, 06824, United States

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Hollywood, Florida, 33021, United States

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Jacksonville, Florida, 32216, United States

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Orlando, Florida, 32806, United States

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Oviedo, Florida, 32765, United States

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Palm Beach Gardens, Florida, 33410, United States

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Atlanta, Georgia, 30342, United States

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Gurnee, Illinois, 60031, United States

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Indianapolis, Indiana, 46256, United States

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Lenexa, Kansas, 66214, United States

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Lexington, Kentucky, 40513, United States

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Baltimore, Maryland, 21208, United States

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Boston, Massachusetts, 02131, United States

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Ann Arbor, Michigan, 48104, United States

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Kalamazoo, Michigan, 49009, United States

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Princeton, New Jersey, 08540, United States

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Albuquerque, New Mexico, 87102, United States

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Williamsville, New York, 14221, United States

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Asheville, North Carolina, 28806, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45245, United States

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Oklahoma City, Oklahoma, 73112, United States

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Philadelphia, Pennsylvania, 19114, United States

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Warwick, Rhode Island, 02886, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Chattanooga, Tennessee, 37421, United States

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Austin, Texas, 78759, United States

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Dallas, Texas, 75214, United States

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Salt Lake City, Utah, 84121, United States

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Virginia Beach, Virginia, 23454, United States

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Seattle, Washington, 98105, United States

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Aalborg, 9000, Denmark

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Ballerup Municipality, 2750, Denmark

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Glostrup Municipality, 2600, Denmark

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Vejle, 7100, Denmark

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Bordeaux, 33076, France

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Nice, 06003, France

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Paris, 75010, France

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Paris, 75014, France

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Pringy, 74374, France

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Athens, 11521, Greece

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Athens, 11525, Greece

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Athens, 16675, Greece

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Thessaloniki, 54645, Greece

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Amadora, 2720-276, Portugal

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Lisbon, 1500-650, Portugal

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Lisbon, 1649-035, Portugal

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Torres Vedras, 2560-280, Portugal

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Moscow, 119435, Russia

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Moscow, 121467, Russia

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Novosibirsk, 630091, Russia

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Saint Petersburg, 197022, Russia

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Ufa, 450083, Russia

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Zaragoza, Aragon, 50009, Spain

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Santander, Cantabria, 39008, Spain

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Valladolid, Castille and León, 47005, Spain

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Barcelona, Catalonia, 08035, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Valencia, Valencia, 46010, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28040, Spain

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Bad Zurzach, 5330, Switzerland

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Biel, 2502, Switzerland

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Geneva, 1205, Switzerland

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Lugano, 6903, Switzerland

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Sankt Gallen, 9007, Switzerland

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Zollikon, 8702, Switzerland

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Related Publications (8)

• 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.

  PMID: 29471679 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 35272533 BACKGROUND

• 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.

  PMID: 35137394 BACKGROUND

• 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.

  PMID: 31707815 BACKGROUND

• 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.

  PMID: 31852816 BACKGROUND

• 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.

  PMID: 35978286 DERIVED

• 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.

  PMID: 34928306 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Migraine Disorders; Headache; Recurrence

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2015
• First Posted: June 29, 2015
• Study Start: July 20, 2015
• Primary Completion: July 11, 2016
• Study Completion: March 20, 2017
• Last Updated: October 12, 2022
• Results First Posted: June 25, 2018

Record last verified: 2022-10

Locations

DK (4); CH (6); GR (4); ES (8); RU (5); PT (4); FR (5); US (40)