Effect of Erenumab-aooe on Disability and Work Productivity in Employed Subjects With Episodic Migraine

Study Overview
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Brief Summary
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To evaluate the effect of erenumab compared to placebo on disability in employed subjects with episodic migraine (EM) who have previously failed 1 or more migraine preventive treatments.

Detailed Description
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Migraine prevention continues to be an area of large, unmet medical need, with existing therapies often having modest efficacy and poor tolerability. Calcitonin gene-related peptide (CGRP) has an important role in the pathophysiology of migraine. Erenumab-aooe is a fully human monoclonal antibody that targets the CGRP receptor, and interrupts its downstream effects. Erenumab has been approved for the preventive treatment of migraine in adults. The present study is a Phase IV trial that will assess the effect of erenumab on disability and work productivity in employed subjects with episodic migraine (EM) who have previously failed 1 or more migraine preventive treatments.

Official Title
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Effect of Erenumab-aooe on Disability and Work Productivity in Employed Subjects With Episodic Migraine Who Have Previously Failed 1 or More Migraine Preventive Treatments.

Conditions
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Migraine

Intervention / Treatment
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* Drug: Placebo
* Drug: Erenumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than or equal to 18 years of age upon entry into screening. Documented history of migraine with or without aura according to the IHS ICHD-III for greater than or equal to 12 months Has EM defined as history of greater than or equal to 4 and less than 15 migraine days and less than 15 headache days per month on average during the 3 months prior to initial screening Employed greater than or equal to 20 hours/week upon entry into initial screening, stable for at least 3 months in the same job and has not specified willful termination of employment throughout the duration of the study. Employment is defined by work outside the home, self-employed, or works from home Has greater than or equal to 4 hours of lost productive time due to headache/migraine and/or related symptoms in the past month prior to initial screening as determined by subject Has total disability score of greater than 10 as assessed by MIDAS (3-month recall) at initial screening History of treatment failure with at least 1 preventive treatment category for migraine Exclusion Criteria: Older than 50 years of age at migraine onset History of cluster headache, hemiplegic migraine, or other trigeminal autonomic cephalalgia. Taken an opioid and/or opioid-containing analgesic greater than or equal to 4 days during the 1 month prior to screening for any indication Taken a butalbital and/or butalbital-containing analgesic greater than or equal to 4 days during the 1 month prior to screening for any indication Change in the regimen of current migraine preventive treatment or a concomitant medication that may have migraine prevention effects during baseline Taken an opioid and/or opioid-containing analgesic ≥ 4 days during baseline for any indication. Taken a butalbital and/or butalbital-containing analgesic ≥ 4 days during baseline for any indication. Previously treated with any agent (monoclonal antibody or small molecule) targeting the CGRP pathway (ligand or receptor) in preventive settings Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>After subjects complete baseline and are found eligible, they will be enrolled and randomized in a 1:1 ratio to either erenumab or placebo. | Drug: Placebo<br>* Placebo once every 4 weeks. SC injection.<br>|
| Experimental: Erenumab<br>After subjects complete baseline and are found eligible, they will be enrolled and randomized in a 1:1 ratio to either erenumab or placebo. | Drug: Erenumab<br>* Erenumab once every 4 weeks. SC injection.<br>* Other names: Aimovig;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Monthly Changes From Baseline in Modified MIDAS Total Score Over the 6-month DBTP | The modified MIDAS Questionnaire is a 5-item questionnaire that measures headache-related disability as lost time from paid work or school, housework, and non-work (family, social, and leisure) activities. Participants provided the number of productive days lost or productivity reduced by half or more over the past month due to headache (item score range from 0 to 31). Productive days lost counted in items 1 and 3 were not included for items 2 and 4, respectively. The 5 item scores were summed to calculate the MIDAS total score (range from 0 to 93). The change from baseline was calculated by subtracting the baseline total score from the total score calculated each month. The change from baseline values for Months 1 to 6 were then summed to calculate the sum of monthly changes from baseline (range from -558 to 558). A negative sum of changes from baseline indicated a better outcome. | Baseline and Months 1 to 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean MMD Over Months 4, 5, and 6 of the 6-month 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) or received migraine-specific medication during aura. A qualified migraine headache was defined either as a migraine (≥30 minutes) with or without aura. 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 phase subtract the number of migraine days during the 4-week baseline phase. A negative change from baseline indicates a better outcome. | Baseline and the last 3 months (months 4, 5, and 6) of the 6-month DBTP | 
| Change From Baseline in Mean Monthly Percent Work Impairment Over Months 4, 5, and 6 of the 6-month DBTP | Percent work impairment was calculated based on questions 2, 4 and 5 of the Work Productivity and Activity Impairment (WPAI) Migraine-Questionnaire and could range from 0% to 100%. The questionnaire was collected weekly. The monthly percent work impairment was equal to the arithmetic mean of the observed weekly percent work impairment over the monthly interval. Higher scores indicate greater impairment. Change from baseline in mean monthly percent work impairment was calculated as the average of monthly percent work impairment over the last 3 months (month 4, 5, and 6) of the 24-week double-blind treatment phase minus the baseline score. A negative change from baseline indicates a better outcome. | Baseline and the last 3 months (months 4, 5, and 6) of the 6-month DBTP | 
| Change From Baseline in Mean MFIQ Physical Functioning Domain Score Over Months 4, 5, and 6 of the 6-month DBTP | The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning. Participants responded to 5 items on the impact on physical functioning domain using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. The scores were calculated as the sum of the item responses rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden. The MFIQ physical functioning domain score was calculated per month for months 4, 5, and 6 and the mean over this period was calculated. The MFIQ physical functioning domain score during the 4-week baseline period was then subtracted to calculate the change from baseline in mean MFIQ physical functioning domain score over months 4, 5,and 6 of the 6-month DBTP. A negative change from baseline indicates a better outcome. | Baseline and the last 3 months (months 4, 5, and 6) of the 6-month DBTP | 
| Change From Baseline in Mean MFIQ Usual Activities Domain Score Over Months 4, 5, and 6 of the 6-month DBTP | The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning. Participants responded to 10 items on the impact on usual activities domain using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. The scores were calculated as the sum of the item responses rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden. The MFIQ usual activities domain score was calculated per month for months 4, 5, and 6 and the mean over this period was calculated. The MFIQ usual activities domain score during the 4-week baseline period was then subtracted to calculate the change from baseline in mean MFIQ usual activities domain score over months 4, 5,and 6 of the 6-month DBTP. A negative change from baseline indicates a better outcome. | Baseline and the last 3 months (months 4, 5, and 6) of the 6-month DBTP | 
| Change From Baseline in Mean MFIQ Social Functioning Domain Score Over Months 4, 5, and 6 of the 6-month DBTP | The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning. Participants responded to 5 items on the impact on social functioning domain using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. The scores were calculated as the sum of the item responses rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden. The MFIQ social functioning domain score was calculated per month for months 4, 5, and 6 and the mean over this period was calculated. The MFIQ social functioning domain score during the 4-week baseline period was then subtracted to calculate the change from baseline in mean MFIQ social functioning domain score over months 4, 5,and 6 of the 6-month DBTP. A negative change from baseline indicates a better outcome. | Baseline and the last 3 months (months 4, 5, and 6) of the 6-month DBTP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Episodic migraine, Disability, Migraine-related disability, Work productivity, Erenumab, AIMOVIG