A Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic 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 the number of monthly migraine days in adults with chronic migraine.

Detailed Description
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This study consisted of the following phases: screening, 4-week baseline phase, 12-week double-blind treatment, and 12-week follow-up. Participants may have elected to participate in the optional pharmacokinetic substudy and the optional, novel patient-reported outcome (PRO) assessment substudy. Participants who completed the 12-week double-blind treatment phase of Study 20120295 were eligible to enroll in an open-label extension study (Study 20130255; NCT02174861).

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Chronic Migraine Prevention

Conditions
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Treatment for Prevention of Chronic Migraine

Intervention / Treatment
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* Biological: Erenumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of at least 5 attacks of migraine without aura and/or migraine with visual sensory, speech and/or language, retinal or brainstem aura. History of ≥ 15 headache days per month of which ≥ 8 headache days were assessed by the subject as migraine day. ≥ 4 distinct headache episodes, each lasting ≥ 4 hours OR if shorter, associated with use of a triptan or ergot-derivative on the same calendar day based on the eDiary calculations. Demonstrated at least 80% compliance with the eDiary. Exclusion Criteria: History of cluster headache or hemiplegic migraine headache Unable to differentiate migraine from other headaches Failed > 3 medication categories due to lack of efficacy for prophylactic treatment of migraine . Received botulinum toxinin head or neck region within 4 months prior to screening. Used a prohibited migraine prophylactic medication, device or procedure within 2 months prior to the start of the baseline phase

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


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. | Drug: Placebo<br>* Administered once a month subcutaneously by authorized investigational site study staff.<br>|
| Experimental: Erenumab 70 mg<br>Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection. | Biological: Erenumab<br>* Administered once a month subcutaneously by authorized investigational site study staff.<br>* Other names: Aimovig™;|
| Placebo Comparator: Erenumab 140 mg<br>Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection. | Biological: Erenumab<br>* Administered once a month subcutaneously by authorized investigational site study staff.<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 | 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 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 treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Baseline | 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 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 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 treatment phase | 
| Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days | 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. | 4-week baseline phase and the last 4 weeks of the 12-week treatment phase | 
| Change From Baseline in Cumulative Monthly Headache Hours | The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or a headache of any duration for which acute headache treatment was administered. | 4-week baseline phase and the last 4 weeks of the 12-week 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 the first dose of study drug up to 16 weeks after the last dose (24 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. | Baseline and weeks 2, 4, 8, 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Migraine