A Controlled Trial of Erenumab in Migraine Prevention

A Phase 3 Japanese Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention

The purpose of this study was to assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Erenumab

Detailed Description

Migraine prevention is an area of a large unmet medical need, with existing therapies often having modest efficacy and poor tolerability. Calcitonin gene-related peptide (CGRP) receptor antagonism is a novel approach to migraine preventive therapy. Erenumab is a human monoclonal antibody against canonical CGRP receptor. The present study is a phase 3 trial intended to assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).

The study consists of a screening period (up to 7 weeks, including a 4-week baseline period), a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP), and an 8-week safety follow-up period (12 weeks after the last dose of investigational product).

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 790-0925
      • Research Site
  • Fukuoka
    • Kasuga-shi, Fukuoka, Japan, 816-0802
      • Research Site
    • Kasuga-shi, Fukuoka, Japan, 816-0824
      • Research Site
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 730-0031
      • Research Site
    • Hiroshima-shi, Hiroshima, Japan, 730-0845
      • Research Site
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 003-0003
      • Research Site
    • Sapporo-shi, Hokkaido, Japan, 007-0836
      • Research Site
    • Sapporo-shi, Hokkaido, Japan, 060-8570
      • Research Site
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 658-0064
      • Research Site
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan, 929-0342
      • Research Site
  • Iwate
    • Morioka-shi, Iwate, Japan, 020-8505
      • Research Site
  • Kagawa
    • Takamatsu-shi, Kagawa, Japan, 769-0103
      • Research Site
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 892-0844
      • Research Site
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 216-8511
      • Research Site
    • Kawasaki-shi, Kanagawa, Japan, 211-8588
      • Research Site
  • Kochi
    • Kochi-shi, Kochi, Japan, 780-8011
      • Research Site
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 861-2101
      • Research Site
    • Kumamoto-shi, Kumamoto, Japan, 862-8505
      • Research Site
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 600-8811
      • Research Site
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 982-0014
      • Research Site
  • Oita
    • Oita-shi, Oita, Japan, 870-0831
      • Research Site
  • Osaka
    • Osaka-shi, Osaka, Japan, 556-0017
      • Research Site
    • Toyonaka-shi, Osaka, Japan, 560-0012
      • Research Site
  • Saga
    • Saga-shi, Saga, Japan, 840-0806
      • Research Site
  • Saitama
    • Iruma-gun, Saitama, Japan, 350-0495
      • Research Site
    • Saitama-shi, Saitama, Japan, 338-8577
      • Research Site
    • Tokorozawa-shi, Saitama, Japan, 359-1141
      • Research Site
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan, 420-0853
      • Research Site
  • Tochigi
    • Shimotsuga-gun, Tochigi, Japan, 321-0293
      • Research Site
  • Tokyo
    • Chofu-shi, Tokyo, Japan, 182-0006
      • Research Site
    • Hachioji-shi, Tokyo, Japan, 192-0032
      • Research Site
    • Minato-ku, Tokyo, Japan, 108-0075
      • Research Site
    • Minato-ku, Tokyo, Japan, 108-8642
      • Research Site
    • Shibuya-ku, Tokyo, Japan, 151-0051
      • Research Site
    • Shinjuku-ku, Tokyo, Japan, 160-0017
      • Research Site
  • Tottori
    • Tottori-shi, Tottori, Japan, 680-0045
      • Research Site
    • Yonago-shi, Tottori, Japan, 683-0033
      • Research Site
  • Toyama
    • Toyama-shi, Toyama, Japan, 930-0803
      • Research Site
  • Yamaguchi
    • Hofu-shi, Yamaguchi, Japan, 747-0802
      • Research Site
    • Yamaguchi-shi, Yamaguchi, Japan, 754-0002
      • Research Site
  • Yamanashi
    • Kai-shi, Yamanashi, Japan, 400-0124
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
• Japanese subjects greater than or equal to 20 to less than or equal to 65 years of age upon entry into screening.
• History of migraine (with or without aura) for greater than or equal to 12 months before screening according to the International Headache Society Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self-report

• Migraine frequency: Chronic Migraine (CM) or Episodic Migraine (EM) over the 3 months before screening based on the following criteria:

  1. CM is defined as greater than or equal to 15 headache days per month of which greater than or equal to 8 headache days on average across the 3 months meet criteria as migraine days
  2. EM is defined as less than 15 headache days per month of which at least 4 or more headache days on average across the 3 months meet criteria as migraine days

Exclusion Criteria:

• Subjects greater than 50 years of age at migraine onset.
• History of cluster headache or hemiplegic migraine headache.
• Unable to differentiate migraine from other headaches.
• Migraine with continuous pain, in which the subject does not experience any pain-free periods (of any duration) during the 1 month before the screening period.
• Malignancy, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.

Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erenumab; Participants were to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Drug: Erenumab; Administered by subcutaneous injection once a month; Other Names: AMG 334; Aimovig®
Placebo Comparator: Placebo; Participants were to receive placebo to erenumab once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period.	Drug: Placebo; Administered by subcutaneous injection once a month; 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
Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period	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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria: ≥ 2 of the following pain features:unilateralthrobbingmoderate to severeexacerbated with exercise/physical activity; ≥ 1 of the following associated symptoms:nauseavomitingphotophobia and phonophobia The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period.	4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP	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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria: ≥ 2 of the following pain features:unilateralthrobbingmoderate to severeexacerbated with exercise/physical activity; ≥ 1 of the following associated symptoms:nauseavomitingphotophobia and phonophobia	4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP	An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine). The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period.	4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, 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.
• Hirata K, Takeshima T, Sakai F, Imai N, Matsumori Y, Tatsuoka Y, Numachi Y, Yoshida R, Peng C, Mikol DD, Lima GPDS, Cheng S. Early onset of efficacy with erenumab for migraine prevention in Japanese patients: Analysis of two randomized, double-blind, placebo-controlled studies. Brain Behav. 2022 Mar;12(3):e2526. doi: 10.1002/brb3.2526. Epub 2022 Feb 24.
• Hiramatsu K, Onizuka Y, Hasebe M, Yoshida R, Numachi Y. Novel Drug for Migraine Prophylaxis: Mode of Action, Efficacy and Safety of Erenumab. Shinryo to Shinyaku (Med Cons New-Remed) 2021:58(11):797-832
• Hirata K, Sakai F, Takeshima T, Imai N, Matsumori Y, Yoshida R, Numachi Y, Peng C, Mikol DD, Cheng S. Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial. J Headache Pain. 2021 Sep 18;22(1):110. doi: 10.1186/s10194-021-01313-8.
• Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD. Erenumab treatment for migraine prevention in Japanese patients: Efficacy and safety results from a Phase 3, randomized, double-blind, placebo-controlled study. Headache. 2021 Jun;61(6):927-935. doi: 10.1111/head.14138. Epub 2021 Jun 21.
• Hirata K, Takeshima T, Sakai F, Numachi Y, Yoshida R, Koukakis R, Hasebe M, Yui D, da Silva Lima GP, Cheng S. Long-term efficacy and safety of erenumab in Japanese patients with episodic and chronic migraine: results from a 28-week open-label treatment period of a randomised trial. BMJ Open. 2023 Aug 18;13(8):e068616. doi: 10.1136/bmjopen-2022-068616.
• Kitamura S, Takeshima T, Yui D, da Silva Lima GP, Koukakis R, Peng C, Yoshida R, Numachi Y, Hasebe M. Efficacy of Erenumab for Migraine Prevention in Japanese Patients with Episodic and Chronic Migraine: Results of a Post-Hoc Pooled Analysis. Neurol Ther. 2023 Dec;12(6):1993-2006. doi: 10.1007/s40120-023-00538-w. Epub 2023 Sep 12.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2019
• Primary Completion (Actual): March 16, 2020
• Study Completion (Actual): November 25, 2020

Study Registration Dates

• First Submitted: January 18, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• 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: 20170609

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either

1. the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or
2. clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes