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

Study Overview
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Brief Summary
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To evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days, in adults with episodic migraine.

Detailed Description
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Adults with a history of migraine with or without aura for ≥ 12 months and who experience ≥ 4 to < 15 migraine days per month with < 15 headache days per month will be randomized 1:1 to placebo or erenumab. Double-blind erenumab or placebo will be administered during the 12-week double-blind treatment phase and open-label erenumab will be administered during the 28-week open-label treatment phase.

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 migraines (with or without aura) for ≥ 12 months Migraine frequency: ≥ 4 and < 15 migraine days per month on average acrossthe 3 months prior to screening Headache (ie, migraine and non-migraine headache) frequency: < 15 headache days per month on average across the 3 months prior to screening Demonstrated 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 headaches No therapeutic response with > 2 categories for prophylactic treatment of migraine after an adequate therapeutic trial. 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 Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase. Received botulinum toxin Anticipated to require any excluded medication, device, or procedure during the study. Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain). History of major psychiatric disorder. History of seizure disorder or other significant neurological conditions other than migraine. Human immunodeficiency virus (HIV) infection by history. Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening. The subject is at risk of self-harm or harm to others. Previously randomized into an AMG 334 study. Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures.

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 on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. At week 12 participants began treatment with erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase. | Drug: Placebo<br>* Administered once a month by subcutaneous injection<br>|
| Experimental: Erenumab<br>Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants continued to receive erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase. | Drug: Erenumab<br>* Administered once a month by subcutaneous injection<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 Monthly Migraine Days at Week 12 | 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 number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase. | 4-week baseline phase and the last 4 weeks of the 12-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 at Week 12 | 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. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of double-blind treatment. 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 4 weeks of the 12-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%. | 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase | 
| Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days at Week 12 | 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 number of migraine-specific treatment days during the last 4 weeks of the 12-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 4 weeks of the 12-week double-blind treatment phase | 
| Percentage of Participants With at Least a 5-point Reduction From Baseline in Average Impact on Everyday Activities Domain Score Measured by MPFID at Week 12 | 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. Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was ≤ -5. | 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase | 
| Percentage of Participants With at Least a 5-Point Reduction From Baseline in Average Impact on Physical Impairment Domain Score Measured by MPFID at Week 12 | 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. Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was ≤ -5. | 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase | 
| Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE. | From first dose of study drug up to 12 weeks after the last dose. The double-blind treatment phase was 12 weeks and the open-label treatment phase was 28 weeks. | 
| Number of Participants Who Developed Antibodies to Erenumab | Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Transient indicates a negative result at the participant's last time point tested, for those participants with a positive binding/neutralizing result post-baseline. | Baseline (the period prior to the first dose erenumab 70 mg) and post-baseline (the period after the first dose of erenumab 70 mg until 12 weeks after last dose, up to 48 weeks total) | 

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