A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache

Study Overview
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Brief Summary
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Study 20170703 is a phase 4, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of erenumab against placebo in participants with chronic migraine (CM) who have a history of at least 1 preventive treatment failure and are diagnosed with medication overuse headache (MOH).

Detailed Description
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Study 20170703 is a phase 4, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the safety and efficacy of erenumab against placebo in a CM population with MOH and prior history of treatment failure. Participants will be enrolled based on fulfilment of the International Classification of Headache Disorders, 3rd Edition (ICHD-3) CM and MOH criteria and will not be advised to early discontinue acute medication. Participants who successfully complete the 24-week double-blind treatment period (DBTP) of the study will be offered an opportunity to continue in an open-label treatment period (OLTP) of 28-weeks duration. Participants who received erenumab treatment during the DBTP will continue to receive the same erenumab dose during the OLTP. Participants who received placebo during the DBTP will be allocated in a 1:1 ratio to receive either erenumab 70 mg or 140 mg SC QM during the OLTP. All participants will remain blinded to their original DBTP treatment assignment.

Official Title
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A Phase 4, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Chronic Migraine and Medication Overuse Headache

Conditions
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Migraine Headache

Intervention / Treatment
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* Drug: Erenumab 70 mg
* Drug: Erenumab 140 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Eligibility criteria will be evaluated during the up to 3-week screening period (part 1) and a 4-week baseline period (part 2). At the end of baseline period, participants who successfully met eligibility criteria will be randomized on study. Key Inclusion Criteria Part 1: To be assessed during the 3-week screening period, prior to the baseline period. Participants are eligible to be included in the study only if all of the following criteria apply: Participant has provided informed consent prior to initiation of any study-specific activities/procedures Age ≥ 18 years on entry into the study Documented history of migraine without aura and/or migraine with aura according to the ICHD-3 classification for ≥ 12 months at screening Documented history of CM for a minimal duration of 6 months before screening Current diagnosis of MOH History of treatment failure with at least 1 preventive treatment as defined as treatment discontinuation due to lack of efficacy, adverse event or general poor tolerability Key Exclusion Criteria Part 1 Participants are excluded from the study if any of the following criteria apply: Disease Related Age > 50 years at migraine onset or > 65 years at CM onset History of hemiplegic migraine, cluster headache or other trigeminal autonomic cephalalgia Current concomitant diagnosis of a secondary type of headache other than MOH No therapeutic response in prevention of migraine after an adequate therapeutic trial of > 3 preventive treatment categories Changes in drug regimen (ie, changes in dose or frequency of use) of an allowed migraine preventive medication within 2 months prior to start of baseline Received botulinum toxin in the head and/or neck region within 4 months prior to screening Documented history of treatment with an anti-calcitonin gene-related peptide product preventive treatment Anticipated to require any excluded medication/device or procedure during the study Other Medical Conditions History or evidence of unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen's physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion Evidence of recreational use of illicit drugs within 12 months prior to screening, based on medical records, self-report, or a positive drug test performed during screening. Key Inclusion Criteria Part 2. To be assessed at the end of the baseline period and prior to enrollment into DBTP. Based on information collected through the electronic diary (eDiary) during the baseline period, the following requirements must be met: -≥ 14 headache days during the 28-day baseline period out of which ≥ 8 headache days meet criteria as migraine days Observation of acute migraine medication overuse during the baseline period. Medication overuse at baseline is defined as: ≥ 10 days of combination treatment OR ≥ 10 days of short-acting opioids/opioid-containing medication OR ≥ 10 days of triptans, ergots, OR ≥ 15 days of nonsteroidal anti-inflammatory drugs or simple analgesics intake At least 2 acute headache medication days per week for each week with at least 5 diary days Demonstrated at least 80% compliance with the eDiary (eg, must complete eDiary items on at least 23 out of 28 days during the baseline period) Key Exclusion Criteria Part 2 Study Procedures Changed or planning to change the dose of an allowed concomitant medication that may have migraine preventive effect during baseline period or post-randomization Unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion Contraception, pregnancy or breastfeeding Unwillingness to maintain acceptable contraception method, when applicable Evidence of pregnancy or breastfeeding per participant self-report, medical records or positivity on baseline pregnancy screening tests, through end of study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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>After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo. | Drug: Placebo<br>* Placebo once every 4 weeks. Subcutaneous injection.<br>|
| Active Comparator: Erenumab 70 mg<br>After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo. | Drug: Erenumab 70 mg<br>* Erenumab once every 4 weeks. Subcutaneous injection.<br>* Other names: Aimovig;|
| Active Comparator: Erenumab 140 mg<br>After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo. | Drug: Erenumab 140 mg<br>* Erenumab once every 4 weeks. Subcutaneous injection.<br>* Other names: Aimovig;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Absence of Medication Overuse Headaches (MOH) at Month 6 | Absence of MOH at month 6 was defined as mean monthly acute headache medication days (AHMD) < 10 days over months 4, 5, and 6 (weeks 13 through 24) or mean monthly headache days < 14 days over months 4, 5, and 6 (weeks 13 through 24) of the DBTP where an AHMD was defined as a calendar day in which the participant took at least 1 acute headache medication. | Months 4, 5, and 6 (weeks 13 through 24) of the DBTP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Monthly AHMDs Over Months 4, 5, and 6 | An AHMD was defined as a calendar day in which the participant takes at least 1 acute headache medication. Acute headache medications included triptan-based, ergotamine-based and ditan-based migraine medications, non-opioid and opioid-containing acute headache medications, non-opioid butalbital and opioid-containing butalbital containing medications. | Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP | 
| Number of Participants With Sustained MOH Remission at Month 6 | Sustained MOH remission was defined as the absence of MOH at month 3 (week 12) and month 6 (week 24) of the DBTP. Absence of MOH was achieved when mean monthly AHMD < 10 days or mean monthly headache days < 14 days over the 3-month period (weeks 12 to 24). | Month 3 (week 12) to month 6 (week 24) of the DBTP | 
| Change From Baseline in Mean Monthly Average Physical Impairment Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID) | The MPFID is a self-administered 13-item instrument measuring physical functioning, completed daily using the eDiary. The physical impairment domain includes 5 items. Participants respond to items using a 5-point scale, with difficulty items ranging from Without any difficulty to Unable to do, and frequency items ranging from None of the time to All of the time. Each item is assigned a score from 1 to 5, with 5 representing the greatest burden. For each domain, the scores are calculated as the sum of the item responses and the sum is rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden. | Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP | 
| Change From Baseline in Mean Monthly Average Impact on Everyday Activities Domain Scores as Measured by the MPFID | The MPFID is a self-administered 13-item instrument measuring physical functioning, completed daily using the eDiary. The impact on everyday activities domain includes 7 items. Participants respond to items using a 5-point scale, with difficulty items ranging from Without any difficulty to Unable to do, and frequency items ranging from None of the time to All of the time. Each item is assigned a score from 1 to 5, with 5 representing the greatest burden. For each domain, the scores are calculated as the sum of the item responses and the sum is rescaled to a 0 to 100 scale, with higher scores representing greater impact of migraine, i.e., higher burden. | Baseline and months 4, 5, and 6 (weeks 13 through 24) of the DBTP | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the DBTP | TEAEs were defined as any adverse event (AE) that started on or after first dose of IP, and up to the end of the DBTP. Participants who experienced any TEAE during the DBTP are presented. Any clinically significant changes in vital signs were included as TEAEs. | Day 1 to Week 24 of the DBTP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Migraine, Medication Overuse Headache