Erenumab - Comprehensive Assessment of Efficacy in (High-Frequency) Episodic Migraine

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity.

Official Title
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Comprehensive Assessment of Erenumab Efficacy in Subjects With High Frequency Episodic Migraine With at Least 1 Previously Failed Preventive Treatment: a Global, Double-blind, Placebo-controlled Phase 4 Study

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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Key inclusion criteria include: Age greater than or equal to 18 years upon entry into initial screening. Documented history of migraine with or without aura according to the International Headache Society (IHS) International Classification of Headache Disorders, Third Edition (ICHD-III) for greater than or equal to 12 months. Have high-frequency episodic migraine (HFEM): Defined as history of ≥ 7 to < 15 migraine days and < 15 headache days per month on average during the 3 months prior to screening. History of ≥ 4 migraine attacks of at least moderate severity per month on average during the 3 months prior to screening. History of treatment failure with at least 1 preventive treatment for migraine. Failure of preventive treatment for migraine is defined as treatment discontinuation due to lack of efficacy, adverse event, or general poor tolerability. Regular use of an oral triptan (using only eletriptan, rizatriptan, sumatriptan, or zolmitriptan) for acute migraine treatment, and typically initiating acute treatment with an oral triptan on > 50% of attacks of at least moderate pain intensity. Regular use is defined as ≥ 4 days of oral triptan use per month during the 3 months prior to screening. Key exclusion criteria include: History of hemiplegic migraine, cluster headache, or other trigeminal autonomic cephalalgia. Has any medical contraindication to the use of an oral triptan. Previously treated with erenumab. Previously treated with a gepant (small molecule calcitonin gene related peptide receptor [CGRP-R] antagonist) in a preventive fashion in a manner consistent with migraine prevention that either: In the opinion of the investigator, did not offer any evidence of a therapeutic response or Was discontinued for less than 12 weeks from the date of initial screening or Was previously discontinued due to a known adverse drug reaction Currently being treated with lasmiditan and/or a gepant in the acute setting. No therapeutic response with greater than 4 of the defined medication categories after an adequate therapeutic trial. Currently has a history of consistent excellent response to oral triptans, defined as achievement of pain-freedom in ≤ 1 hour for ≥ 50% of treated attacks of at least moderate pain intensity during the 3 months prior to screening. Use of triptans administered via a non-oral (e.g. subcutaneous [SC] or intranasal delivery systems) or sublingual route at the time of screening, during the run-in and baseline periods, and throughout the study duration.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erenumab<br>The 4-month DBTP has 2 phases: Main double-blind treatment phase (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment. Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden. | Drug: Erenumab<br>* 140 mg, 2 consecutive injections of 70 mg<br>|
| Experimental: Placebo<br>The 4-month DBTP has 2 phases: Main DBTP (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment. Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden. | Drug: Placebo<br>* 2 consecutive injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean monthly hours of at least moderate headache pain intensity, with pain intensity measured by the 11-point NRS scale | To evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity | Over months 1, 2, and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean monthly physical function domain score as measured by the Migraine Functional Impact Questionnaire (MFIQ) | To evaluate the treatment benefit of erenumab on functional impairment | Over months 1, 2, and 3 | 
| Change from baseline in the mean monthly impact on usual activities domain score as measured by the MFIQ | To evaluate the treatment benefit of erenumab on functional impairment | Over months 1, 2, and 3 | 
| Change from baseline in the mean monthly impact on emotional function domain score as measured by the MFIQ | To evaluate the treatment benefit of erenumab on functional impairment | Over months 1, 2, and 3 | 
| Change from baseline in the mean monthly impact on social function domain score as measured by the MFIQ | To evaluate the treatment benefit of erenumab on functional impairment | Over months 1, 2, and 3 | 
| Change from baseline in mean monthly average duration of at least moderate pain intensity in qualifying migraine attacks, with pain measured by the 11-point NRS scale | To evaluate the treatment benefit of erenumab on duration of migraine pain of at least moderate intensity | Over months 1, 2, and 3 | 
| Change from baseline in mean monthly average peak migraine pain intensity as assessed by the 11-point Numeric Rating Scale (NRS) | To evaluate the treatment benefit of erenumab on peak migraine pain intensity | Over months 1, 2, and 3 |