A Controlled Trial of Erenumab in Migraine Prevention

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03812224
• Other study ID #: 20170609
• Status: Completed
• Phase: Phase 3
• Start date: April 12, 2019
• Est. completion date: November 25, 2020

Study information

• Verified date: February 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: November 25, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Administered by subcutaneous injection once a month
• Placebo
Administered by subcutaneous injection once a month

Locations

Country	Name	City	State
Japan	Research Site	Chofu-shi	Tokyo
Japan	Research Site	Hachioji-shi	Tokyo
Japan	Research Site	Hiroshima-shi	Hiroshima
Japan	Research Site	Hiroshima-shi	Hiroshima
Japan	Research Site	Hofu-shi	Yamaguchi
Japan	Research Site	Iruma-gun	Saitama
Japan	Research Site	Kagoshima-shi	Kagoshima
Japan	Research Site	Kahoku-gun	Ishikawa
Japan	Research Site	Kai-shi	Yamanashi
Japan	Research Site	Kasuga-shi	Fukuoka
Japan	Research Site	Kasuga-shi	Fukuoka
Japan	Research Site	Kawasaki-shi	Kanagawa
Japan	Research Site	Kawasaki-shi	Kanagawa
Japan	Research Site	Kobe-shi	Hyogo
Japan	Research Site	Kochi-shi	Kochi
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kumamoto-shi	Kumamoto
Japan	Research Site	Kyoto-shi	Kyoto
Japan	Research Site	Matsuyama-shi	Ehime
Japan	Research Site	Minato-ku	Tokyo
Japan	Research Site	Minato-ku	Tokyo
Japan	Research Site	Morioka-shi	Iwate
Japan	Research Site	Oita-shi	Oita
Japan	Research Site	Osaka-shi	Osaka
Japan	Research Site	Saga-shi	Saga
Japan	Research Site	Saitama-shi	Saitama
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sendai-shi	Miyagi
Japan	Research Site	Shibuya-ku	Tokyo
Japan	Research Site	Shimotsuga-gun	Tochigi
Japan	Research Site	Shinjuku-ku	Tokyo
Japan	Research Site	Shizuoka-shi	Shizuoka
Japan	Research Site	Takamatsu-shi	Kagawa
Japan	Research Site	Tokorozawa-shi	Saitama
Japan	Research Site	Tottori-shi	Tottori
Japan	Research Site	Toyama-shi	Toyama
Japan	Research Site	Toyonaka-shi	Osaka
Japan	Research Site	Yamaguchi-shi	Yamaguchi
Japan	Research Site	Yonago-shi	Tottori

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Japan, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: unilateral; throbbing; moderate to severe; exacerbated with exercise/physical activity; = 1 of the following associated symptoms: nausea; vomiting; photophobia 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	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: unilateral; throbbing; moderate to severe; exacerbated with exercise/physical activity; = 1 of the following associated symptoms: nausea; vomiting; photophobia and phonophobia	4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period
Secondary	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

External Links

•   AmgenTrials clinical trials website