Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention

Study Overview
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Brief Summary
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The primary objective of the study was to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days.

Detailed Description
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This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The trial consisted of four phases: screening (≤ 3 weeks of initial screening and a 4-week baseline phase); the double-blind treatment phase (24 weeks) in which participants received placebo or erenumab 70 mg or 140 mg daily; the active-treatment phase, in which participants underwent repeat randomization and were assigned to receive 70 mg or 140 mg of erenumab (28 weeks); and a safety follow-up phase (12 weeks).

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 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: History of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-3) classification Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening and during baseline Headache frequency: < 15 headache days per month on average across the 3 months prior to screening and baseline Demonstrated at least 80% compliance with the eDiary. Exclusion Criteria: Older than 50 years of age at migraine onset History of cluster headache or hemiplegic migraine headache Unable to differentiate migraine from other headache No therapeutic response with > 2 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase Concomitant use of 2 or more medications with possible migraine prophylactic effects within 2 months prior to the start of the baseline phase or during the baseline phase. If only 1 prophylactic medication is used, the dose must be stable within 2 months prior to the start of the baseline phase and throughout the study

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded. | Drug: Placebo<br>* Administered by subcutaneous injection once a month<br>|
| Experimental: Erenumab 70 mg QM<br>Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded. | Drug: Erenumab<br>* Administered by subcutaneous injection once a month<br>* Other names: Aimovig™;|
| Experimental: Erenumab 140 mg QM<br>Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. At week 24, participants were re-randomized to receive either erenumab 70 mg or erenumab 140 mg, administered QM at weeks 24, 28, 32, 36, 40, 44, and 48, with actual dose blinded. | Drug: Erenumab<br>* Administered by subcutaneous injection once a month<br>* Other names: Aimovig™;|

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 to the Last 3 Months 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. 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 - the number of migraine days during the 4-week baseline phase. | 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase | 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 without aura or a migraine with aura. At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%. | 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase | 
| Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period | Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. 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 phase - the number of migraine-specific treatment days during the 4-week baseline phase. | 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase | 
| Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase | The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from Without any difficulty (1) to Unable to do (5) and frequency items ranging from None of the time (1) to All of the time (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine. Change from baseline was calculated as (mean monthly average physical impairment scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly average physical impairment scores as measured by the MPFID). | 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase | 
| Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase | The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from Without any difficulty (1) to Unable to do (5) and frequency items ranging from None of the time (1) to All of the time (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine. Change from baseline was calculated as (mean monthly impact on everyday activities scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly impact on everyday activities scores as measured by the MPFID). | 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Headache, Prevention, Prophylaxis