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

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.

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03912337

Enrollment

Registered

2019-04-11

Start date

2019-12-04

Completion date

2021-07-28

Last updated

2022-07-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Keywords

Episodic migraine, Disability, Migraine-related disability, Work productivity, Erenumab, AIMOVIG

Brief summary

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

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.

Interventions

DRUGPlacebo

Placebo once every 4 weeks. SC injection.

DRUGErenumab

Erenumab once every 4 weeks. SC injection.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Sum of Monthly Changes From Baseline in Modified MIDAS Total Score Over the 6-month DBTP	Baseline and Months 1 to 6	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Mean MMD Over Months 4, 5, and 6 of the 6-month DBTP	Baseline and the last 3 months (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.
Change From Baseline in Mean Monthly Percent Work Impairment Over Months 4, 5, and 6 of the 6-month DBTP	Baseline and the last 3 months (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.
Change From Baseline in Mean MFIQ Physical Functioning Domain Score Over Months 4, 5, and 6 of the 6-month DBTP	Baseline and the last 3 months (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.
Change From Baseline in Mean MFIQ Usual Activities Domain Score Over Months 4, 5, and 6 of the 6-month DBTP	Baseline and the last 3 months (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.
Change From Baseline in Mean MFIQ Social Functioning Domain Score Over Months 4, 5, and 6 of the 6-month DBTP	Baseline and the last 3 months (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.

Countries

United States

Participant flow

Recruitment details

This study was conducted at 13 centers in the United States of America. The study consisted of a 4-week baseline period and a 6-month double-blind treatment period (DBTP).

Pre-assignment details

Eligible participants were randomized in a 1:1 ratio to either erenumab 140 milligrams (mg) or placebo once monthly (QM).

Participants by arm

Arm	Count
Placebo QM Participants randomized to receive placebo QM for 6 months during the DBTP.	15
Erenumab 140 mg QM Participants randomized to receive erenumab 140 mg QM for 6 months during the DBTP.	14
Total	29

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	1
Overall Study	Withdrawal of Consent From Study	1	0

Baseline characteristics

Characteristic	Placebo QM	Erenumab 140 mg QM	Total
Age, Continuous	40.8 years STANDARD_DEVIATION 9.9	38.6 years STANDARD_DEVIATION 15.4	39.7 years STANDARD_DEVIATION 12.7
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants	13 Participants	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
MFIQ - Impact on Social Functioning Domain Score	41.8 score on a scale STANDARD_DEVIATION 18.6	54.2 score on a scale STANDARD_DEVIATION 19.4	47.8 score on a scale STANDARD_DEVIATION 19.7
MFIQ - Impact on Usual Activities Domain Score	38.5 score on a scale STANDARD_DEVIATION 15.5	51.3 score on a scale STANDARD_DEVIATION 20	44.7 score on a scale STANDARD_DEVIATION 18.6
Migraine Functional Impact Questionnaire (MFIQ) - Impact on Physical Functioning Domain Score	46.5 score on a scale STANDARD_DEVIATION 17.9	56.8 score on a scale STANDARD_DEVIATION 23.8	51.5 score on a scale STANDARD_DEVIATION 21.2
Modified Migraine Disability Assessment (MIDAS) Total Score	20.3 score on a scale STANDARD_DEVIATION 11.5	23.1 score on a scale STANDARD_DEVIATION 11.3	21.7 score on a scale STANDARD_DEVIATION 11.3
Monthly Migraine Days (MMD)	9.2 migraine days per month STANDARD_DEVIATION 3.7	9.0 migraine days per month STANDARD_DEVIATION 2.8	9.1 migraine days per month STANDARD_DEVIATION 3.2
Monthly Percent Work Impairment	49.5 percentage of monthly workdays impaired STANDARD_DEVIATION 19	57.6 percentage of monthly workdays impaired STANDARD_DEVIATION 13.5	53.4 percentage of monthly workdays impaired STANDARD_DEVIATION 16.8
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	13 Participants	14 Participants	27 Participants
Sex: Female, Male Female	12 Participants	10 Participants	22 Participants
Sex: Female, Male Male	3 Participants	4 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 14
other Total, other adverse events	7 / 15	9 / 14
serious Total, serious adverse events	0 / 15	0 / 14

Outcome results

Primary

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.

Time frame: Baseline and Months 1 to 6

Population: The respective efficacy analysis set (EAS) consisted of a subset of participants from traditional study sites or DCTS who received at least 1 dose of investigational product (IP) and had a baseline value and at least 1 post baseline value for the endpoint of interest. Participants were analyzed according to their randomized treatment, regardless of the treatment received.

Arm	Measure	Value (MEAN)	Dispersion
Placebo QM	Sum of Monthly Changes From Baseline in Modified MIDAS Total Score Over the 6-month DBTP	-71.17 score on a scale	Standard Deviation 60.81
Erenumab 140 mg QM	Sum of Monthly Changes From Baseline in Modified MIDAS Total Score Over the 6-month DBTP	-98.03 score on a scale	Standard Deviation 71.04

Secondary

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.