A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.

An Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 334

To assess the long-term safety and efficacy of erenumab.

Study Overview

• Status: Completed
• Conditions: Treatment for Prevention of Chronic Migraine
• Intervention / Treatment: Drug: Erenumab

Detailed Description

This was a multicenter, 52-week, open-label study designed to assess the long-term safety and efficacy of erenumab in adults with chronic migraine. Participants who completed the 12-week double-blind treatment of the parent Study 20120295 (NCT02066415) and met all Study 20130255 eligibility criteria were eligible for enrollment into this study. Enrollment occurred within 14 days after the parent study's week 12 visit.

The initial dose used in the study was erenumab 70 mg every month (QM). The protocol was subsequently amended to increase the dose to erenumab 140 mg QM (Protocol Amendment 2). Participants who had already completed the week 28 visit (ie, midpoint of the study) at the time of Protocol Amendment 2 continued to receive open-label erenumab 70 mg QM for the remainder of the study. Participants who enrolled but had not completed the week 28 visit at the time of Protocol Amendment 2 increased the open-label erenumab dose from 70 mg QM to 140 mg QM at the next visit. All participants who enrolled after Protocol Amendment 2 received open-label erenumab 140 mg QM throughout the study.

Participants may elect to participate in a separate clinical home use (CHU) substudy to assess subjects' ability to self-administer 140 mg of erenumab for in-home use using either two prefilled syringes (PFS) or two prefilled autoinjector/pens (AI/pens). Enrollment in the 12-week substudy occurred at either week 12 or week 40 of study 20130255. Participants were randomized to self-administer erenumab using either the PFS or AI/pen on CHU days 29 and 57 at home.

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Research Site
• Czechia
  • Brno, Czechia, 656 91
    • Research Site
  • Brno, Czechia, 611 00
    • Research Site
  • Praha 2, Czechia, 120 00
    • Research Site
  • Praha 4, Czechia, 140 59
    • Research Site
• Denmark
  • Glostrup, Denmark, 2600
    • Research Site
• Finland
  • Helsinki, Finland, 00100
    • Research Site
  • Oulu, Finland, 90101
    • Research Site
  • Tampere, Finland, 33100
    • Research Site
  • Turku, Finland, 20100
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Berlin, Germany, 10435
    • Research Site
  • Bochum, Germany, 44787
    • Research Site
  • Essen, Germany, 45147
    • Research Site
  • Hamburg, Germany, 20251
    • Research Site
  • Kiel, Germany, 24149
    • Research Site
• Norway
  • Lillehammer, Norway, 2629
    • Research Site
  • Sandvika, Norway, 1337
    • Research Site
  • Stavanger, Norway, 4005
    • Research Site
  • Ålesund, Norway, 6003
    • Research Site
• Poland
  • Krakow, Poland, 31-209
    • Research Site
  • Lodz, Poland, 90-338
    • Research Site
  • Lublin, Poland, 20-016
    • Research Site
  • Poznan, Poland, 60-355
    • Research Site
  • Swidnik, Poland, 21-040
    • Research Site
  • Warszawa, Poland, 00-669
    • Research Site
• Sweden
  • Falköping, Sweden, 521 37
    • Research Site
  • Stockholm, Sweden, 141 86
    • Research Site
  • Stockholm, Sweden, 112 45
    • Research Site
  • Stockholm, Sweden, 114 33
    • Research Site
  • Vällingby, Sweden, 162 68
    • Research Site
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Research Site
  • Hull, United Kingdom, HU3 2JZ
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • Stoke on Trent, United Kingdom, ST4 6QG
    • Research Site
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Research Site
    • Palo Alto, California, United States, 94304
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
    • Sherman Oaks, California, United States, 91403
      • Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Orlando, Florida, United States, 32801
      • Research Site
    • Palm Beach Gardens, Florida, United States, 33410
      • Research Site
    • West Palm Beach, Florida, United States, 33407
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Decatur, Georgia, United States, 30033
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Research Site
  • Maryland
    • Pikesville, Maryland, United States, 21208
      • Research Site
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Research Site
    • Worcester, Massachusetts, United States, 01605
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
    • Springfield, Missouri, United States, 65807
      • Research Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Research Site
  • New York
    • Amherst, New York, United States, 14226
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Dallas, Texas, United States, 75214
      • Research Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 66 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has provided informed consent prior to initiation of any study-specific activities/procedures
2. Completed the 12-week study visit and did not end IP early during the double-blind treatment period of the AMG 334 20120295 (NCT02066415) parent study, and is appropriate for continued treatment.

Exclusion Criteria:

1. Development of any unstable or clinically significant medical condition, laboratory or electrocardiogram (ECG) abnormality following randomization into the parent study, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
2. Systolic blood pressure (BP) 160 mm Hg and/or diastolic BP 100 mm Hg or greater at screening/Day 1.
3. Subject who used excluded concomitant medications between week 8 and week 12 of the parent study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Erenumab; Participants received erenumab 70 mg once a month (QM) or 140 mg QM by subcutaneous injection for up to 52 weeks.	Drug: Erenumab; Administered by subcutaneous injection once a month; Other Names: AMG 334; Aimovig™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Adverse events (AEs) were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate AE; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; urgent intervention indicated; Grade 5 = Death related to AE.	From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).
CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use	At the CHU substudy day 28 and day 56 visits, the site provided erenumab 140 mg to participants to self-administer at home on the following day. Study site staff then called the participants and asked if they administered a full, partial, or no dose of erenumab. A full dose was defined when the entire volume of both prefilled syringes or autoinjector/pens were injected.	Day 29 (week 4) and day 57 (week 8) of the substudy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Study 20120295 Baseline in Monthly Migraine Days	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 4 weeks prior to each study visit - the number of migraine days during the 4-week baseline phase.	4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255
Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline	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 4 weeks prior to each study visit. At least a 50% reduction from baseline (of study 20120295) in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the 4 weeks prior to each study visit * 100 / baseline monthly migraine days was less than or equal to -50%.	4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255
Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days	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.	4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255
Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours	The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or; a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or; a headache of any duration for which acute headache treatment was administered.	4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255
CHU Substudy: Number of Participants With Adverse Events	Adverse events were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Injection site reactions were derived from a Medical Dictionary for Regulatory Activities (MedDRA) query using a list of pre-specified preferred terms. An adverse device effect (ADE) is any adverse event related to the use of a medical device.	From first dose of erenumab in the CHU substudy to 28 days after last dose of erenumab in the CHU substudy; up to 12 weeks.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• Tepper SJ, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein SD, Winner P, Zhang F, Cheng S, Mikol DD. Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study. Cephalalgia. 2020 May;40(6):543-553. doi: 10.1177/0333102420912726. Epub 2020 Mar 26.
• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2014
• Primary Completion (ACTUAL): May 26, 2017
• Study Completion (ACTUAL): May 26, 2017

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (ESTIMATE): June 26, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Chronic Migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: 20130255; 2013-005311-27 (EUDRACT_NUMBER)