Clinical trial NCT03812224: A Controlled Trial of Erenumab in Migraine Prevention
Official title: A Phase 3 Japanese Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-01-23
Enrollment: 261
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period
timeFrame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
Secondary outcomes:
measure: 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
timeFrame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
measure: Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP
timeFrame: 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
Other outcomes:
Locations:
city: Matsuyama-shi
country: Japan
facility: Research Site
state: Ehime
city: Kasuga-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Kasuga-shi
country: Japan
facility: Research Site
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Research Site
state: Hiroshima
city: Hiroshima-shi
country: Japan
facility: Research Site
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Research Site
state: Hyogo
city: Kahoku-gun
country: Japan
facility: Research Site
state: Ishikawa
city: Morioka-shi
country: Japan
facility: Research Site
state: Iwate
city: Takamatsu-shi
country: Japan
facility: Research Site
state: Kagawa
city: Kagoshima-shi
country: Japan
facility: Research Site
state: Kagoshima
city: Kawasaki-shi
country: Japan
facility: Research Site
state: Kanagawa
city: Kawasaki-shi
country: Japan
facility: Research Site
state: Kanagawa
city: Kochi-shi
country: Japan
facility: Research Site
state: Kochi
city: Kumamoto-shi
country: Japan
facility: Research Site
state: Kumamoto
city: Kumamoto-shi
country: Japan
facility: Research Site
state: Kumamoto
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto
city: Sendai-shi
country: Japan
facility: Research Site
state: Miyagi
city: Oita-shi
country: Japan
facility: Research Site
state: Oita
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Research Site
state: Osaka
city: Saga-shi
country: Japan
facility: Research Site
state: Saga
city: Iruma-gun
country: Japan
facility: Research Site
state: Saitama
city: Saitama-shi
country: Japan
facility: Research Site
state: Saitama
city: Tokorozawa-shi
country: Japan
facility: Research Site
state: Saitama
city: Shizuoka-shi
country: Japan
facility: Research Site
state: Shizuoka
city: Shimotsuga-gun
country: Japan
facility: Research Site
state: Tochigi
city: Chofu-shi
country: Japan
facility: Research Site
state: Tokyo
city: Hachioji-shi
country: Japan
facility: Research Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Research Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Research Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Research Site
state: Tokyo
city: Tottori-shi
country: Japan
facility: Research Site
state: Tottori
city: Yonago-shi
country: Japan
facility: Research Site
state: Tottori
city: Toyama-shi
country: Japan
facility: Research Site
state: Toyama
city: Hofu-shi
country: Japan
facility: Research Site
state: Yamaguchi
city: Yamaguchi-shi
country: Japan
facility: Research Site
state: Yamaguchi
city: Kai-shi
country: Japan
facility: Research Site
state: Yamanashi
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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: 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.
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.