A Controlled Trial of Erenumab in Migraine Prevention

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Migraine

Intervention / Treatment
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* Drug: Erenumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erenumab<br>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<br>* Administered by subcutaneous injection once a month<br>* Other names: Aimovig®;|
| Placebo Comparator: Placebo<br>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: Erenumab<br>* Administered by subcutaneous injection once a month<br>* Other names: Aimovig®;Drug: Placebo<br>* Administered by subcutaneous injection once a month<br>|

What is the study measuring?
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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: 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 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: 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 | 
| 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 |