Trial Outcomes & Findings for Erenumab - Comprehensive Assessment of Efficacy in (High-Frequency) Episodic Migraine (NCT NCT04252742)
NCT ID: NCT04252742
Last Updated: 2026-03-31
Results Overview
At least moderate headache pain intensity was defined as headache pain intensity reported as 'Moderate' or 'Severe' based on the 3-level headache pain intensity scale. Worst or peak pain intensity during a headache was collected using the e-diary in 3-levels (mild, moderate or severe). The duration of headaches with at least moderate pain intensity was collected. A negative change from baseline indicates a reduction in mean monthly hours of at least moderate headache pain intensity. Change from baseline in mean monthly measurement is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The least squares mean (LSM) estimates of change from baseline in reported headache pain intensity utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
COMPLETED
PHASE4
512 participants
Baseline, Month 1, Month 2, and Month 3
2026-03-31
Participant Flow
This study was conducted at 61 study centers in North America and Europe from September 2020 to October 2023.
Eligible adult participants with high frequency episodic migraine (EP) who met specific eligibility criteria during a 2-week run-in period and 4-week baseline period entered the double-blind treatment period (DBTP). The DBTP included a 12-week main-DBTP (M-DBTP) and a 4-week exploratory DBTP (E-DBTP)
Participant milestones
| Measure |
Placebo
Participants were randomized to receive matching placebo subcutaneously (SC) every 4 weeks (Q4W) for up to 16 weeks.
|
Erenumab 140 mg SC Q4W
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Overall Study
STARTED
|
256
|
256
|
|
Overall Study
Received Investigational Product (IP)
|
256
|
254
|
|
Overall Study
COMPLETED
|
241
|
244
|
|
Overall Study
NOT COMPLETED
|
15
|
12
|
Reasons for withdrawal
| Measure |
Placebo
Participants were randomized to receive matching placebo subcutaneously (SC) every 4 weeks (Q4W) for up to 16 weeks.
|
Erenumab 140 mg SC Q4W
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Overall Study
Decision by sponsor
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
15
|
9
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Participants with observed data within the 4-week baseline period are included.
Baseline characteristics by cohort
| Measure |
Placebo
n=256 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
Erenumab 140 mg SC Q4W
n=256 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Total
n=512 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 10.2 • n=256 Participants
|
41.9 years
STANDARD_DEVIATION 10.9 • n=256 Participants
|
42.2 years
STANDARD_DEVIATION 10.5 • n=512 Participants
|
|
Sex: Female, Male
Female
|
222 Participants
n=256 Participants
|
220 Participants
n=256 Participants
|
442 Participants
n=512 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=256 Participants
|
36 Participants
n=256 Participants
|
70 Participants
n=512 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=256 Participants
|
7 Participants
n=256 Participants
|
14 Participants
n=512 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
248 Participants
n=256 Participants
|
249 Participants
n=256 Participants
|
497 Participants
n=512 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=256 Participants
|
0 Participants
n=256 Participants
|
1 Participants
n=512 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=256 Participants
|
0 Participants
n=256 Participants
|
0 Participants
n=512 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=256 Participants
|
2 Participants
n=256 Participants
|
3 Participants
n=512 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=256 Participants
|
0 Participants
n=256 Participants
|
0 Participants
n=512 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=256 Participants
|
2 Participants
n=256 Participants
|
4 Participants
n=512 Participants
|
|
Race (NIH/OMB)
White
|
253 Participants
n=256 Participants
|
252 Participants
n=256 Participants
|
505 Participants
n=512 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=256 Participants
|
0 Participants
n=256 Participants
|
0 Participants
n=512 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=256 Participants
|
0 Participants
n=256 Participants
|
0 Participants
n=512 Participants
|
|
Monthly Hours of at Least Moderate Headache Pain Intensity
|
47.382 hours/month
STANDARD_DEVIATION 29.302 • n=255 Participants • Participants with observed data within the 4-week baseline period are included.
|
48.843 hours/month
STANDARD_DEVIATION 29.502 • n=256 Participants • Participants with observed data within the 4-week baseline period are included.
|
48.114 hours/month
STANDARD_DEVIATION 29.383 • n=511 Participants • Participants with observed data within the 4-week baseline period are included.
|
PRIMARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP.
At least moderate headache pain intensity was defined as headache pain intensity reported as 'Moderate' or 'Severe' based on the 3-level headache pain intensity scale. Worst or peak pain intensity during a headache was collected using the e-diary in 3-levels (mild, moderate or severe). The duration of headaches with at least moderate pain intensity was collected. A negative change from baseline indicates a reduction in mean monthly hours of at least moderate headache pain intensity. Change from baseline in mean monthly measurement is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The least squares mean (LSM) estimates of change from baseline in reported headache pain intensity utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=253 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=251 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Hours of at Least Moderate Headache Pain Intensity Over Months 1, 2, and 3
|
-31.33 hours/month
Standard Error 1.25
|
-23.38 hours/month
Standard Error 1.26
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP. Data for participants included in the model for the MFIQ Physical Function Domain are presented.
The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including on Physical Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the past 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=244 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=239 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Physical Function Domain Score as Measured by the Migraine Functional Impact Questionnaire (MFIQ) Over Months 1, 2, and 3
|
-30.28 score on a scale
Standard Error 1.23
|
-22.92 score on a scale
Standard Error 1.25
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP. Data for participants included in the model for the MFIQ Usual Activities Domain are presented.
The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Usual Activities (10 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=244 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=239 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Usual Activities Domain Score as Measured by the MFIQ Over Months 1, 2, and 3
|
-31.08 score on a scale
Standard Error 1.16
|
-23.98 score on a scale
Standard Error 1.17
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP. Data for participants included in the model for the MFIQ Emotional Functioning Domain are presented.
The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Emotional Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=244 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=239 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Emotional Functioning Domain Score as Measured by the MFIQ Over Months 1, 2, and 3
|
-29.83 score on a scale
Standard Error 1.33
|
-22.77 score on a scale
Standard Error 1.34
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP. Data for participants included in the model for the MFIQ Social Functioning Domain are presented.
The MFIQ is a self-administered 26-item instrument measuring the impact of migraine on broader functioning including Impact on Social Functioning (5 items). Participants responded to items using a 5-point scale assigned scores from 1 to 5, with 5 representing the greatest burden. Each domain score was calculated as the sum of the item responses and rescaled to a 0 to 100 scale, with higher scores representing greater burden. The recall period was the previous 7 days. A negative change from baseline indicates an improvement in burden. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=244 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=239 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Social Functioning Domain Score as Measured by the MFIQ Over Months 1, 2, and 3
|
-31.87 score on a scale
Standard Error 1.27
|
-25.05 score on a scale
Standard Error 1.28
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP.
At least moderate headache pain intensity was defined as headache pain intensity reported as 'Moderate' or 'Severe' based on the 3-level headache pain intensity scale. Worst or peak pain intensity during a headache was collected using the e-diary in 3-levels (mild, moderate or severe). The duration of headaches with at least moderate pain intensity during a migraine attack was collected. A negative change from baseline indicates a reduction in mean monthly average duration of at least moderate headache pain intensity during a migraine attack. Change from baseline in mean monthly measurement is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=253 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=251 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Average Duration of at Least Moderate Headache Pain Intensity in Migraine Attacks Occurring Over Months 1, 2, and 3
|
-3.86 hours
Standard Error 0.30
|
-2.78 hours
Standard Error 0.31
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 2, and Month 3Population: The M-DBTP efficacy analysis set consisted of a subset the full analysis set (all participants randomized in the study) who received at least 1 dose of IP and had observed monthly hours of at least moderate headache pain intensity at baseline and at least 1 measurement during the M-DBTP.
The NRS assesses headache pain intensity ranging from 0 to 10 with a higher score indicating more severe pain. Participants recorded the pain intensity using the e-diary at the headache end-time or in an evening diary entry on a daily basis for an ongoing headache. A negative change from baseline indicates an improvement in pain intensity. Change from baseline in mean monthly scores is the arithmetic mean of the monthly change from baseline values for the months considered with observed data, if there was at least one observed monthly value. The LSM estimates utilized a linear mixed model which included treatment, visit, treatment-by-visit interaction, and baseline value as covariates and assumed a first-order auto regression covariance structure.
Outcome measures
| Measure |
Erenumab 140 mg SC Q4W
n=253 Participants
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
Placebo
n=251 Participants
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Change From Baseline in Mean Monthly Average Peak Migraine Pain Intensity as Assessed by the 11-point Numeric Rating Scale (NRS) Over Months 1, 2, and 3
|
-1.96 score on a scale
Standard Error 0.13
|
-1.48 score on a scale
Standard Error 0.13
|
Adverse Events
Placebo
Erenumab 140 mg SC Q4W
Serious adverse events
| Measure |
Placebo
n=256 participants at risk
Participants were randomized to receive matching placebo SC QW4 for up to 16 weeks in the DBTP.
|
Erenumab 140 mg SC Q4W
n=254 participants at risk
Participants were randomized to receive 140 mg erenumab SC Q4W for up to 16 weeks in the DBTP.
|
|---|---|---|
|
Infections and infestations
COVID-19 pneumonia
|
0.39%
1/256 • Day 1 to end of the DBTP (up to 16 weeks)
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/254 • Day 1 to end of the DBTP (up to 16 weeks)
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Psychogenic tremor
|
0.39%
1/256 • Day 1 to end of the DBTP (up to 16 weeks)
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/254 • Day 1 to end of the DBTP (up to 16 weeks)
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER