• Number of participants with change from baseline in mean monthly acute headache medication days (AHMD) [ Time Frame: Over Months 4, 5, and 6 (week 13 through 24) of the double-blind treatment phase ]
  Change from baseline in mean monthly AHMD over months 4, 5, and 6 (week 13 through 24) of the DBTP.
• Number of participants with sustained Medication Overuse Headache (MOH) remission [ Time Frame: Over Months 3 (week 12) and 6 (week 24) of the double-blind treatment phase ]
  Sustained MOH remission during DBTP, as defined by absence of MOH at months 3 (week 12) and 6 (week 24) of the DBTP, and "absence of MOH" is achieved when mean monthly AHMD < 10 days OR mean MHD < 14 days over the respective 3-month period.
• Number of participants with change from baseline in mean monthly average physical impairment domain scores as measured by the migraine physical function impact diary (MPFID) [ Time Frame: Over Months 4, 5, and 6 (week 13 through 24) of the double-blind treatment phase ]
  Change from baseline in mean monthly average physical impairment domain scores as measured by the MPFID over months 4, 5, and 6 (week 13 through 24) of the DBTP.
• Number of participants with change from baseline in mean monthly average impact on everyday activities domain scores as measured by the MPFID [ Time Frame: Over Months 4, 5, and 6 (week 13 through 24) of the double-blind treatment phase ]
  Change from baseline in mean monthly average impact on everyday activities domain scores as measured by the MPFID over months 4, 5, and 6 (week 13 through 24) of the DBTP.
• Number of participants with change from baseline in mean HIT-6 score [ Time Frame: Over Months 4, 5, and 6 (week 13 through 24) of the double-blind treatment phase ]
  Change from baseline in mean HIT-6 score over months 4, 5, and 6 (week 13 through 24) of the DBTP.

• Number of participants with change from baseline in mean monthly acute headache medication days (AHMD) [ Time Frame: Over Months 4, 5, and 6 of the double-blind treatment phase ]
  Change from baseline in mean monthly AHMD over months 4, 5, and 6 of the DBTP
• Number of participants with sustained Medication Overuse Headache (MOH) remission [ Time Frame: Over Months 3 and 6 of the double-blind treatment phase ]
  Sustained MOH remission during DBTP, as defined by absence of MOH at months 3 and 6 of the DBTP, and "absence of MOH" is achieved when mean monthly AHMD < 10 days OR mean MHD < 14 days over the respective 3-month period
• Number of participants with change from baseline in mean monthly average physical impairment domain scores as measured by the MPFID [ Time Frame: Over Months 4, 5, and 6 of the double-blind treatment phase ]
  Change from baseline in mean monthly average physical impairment domain scores as measured by the MPFID over months 4, 5, and 6 of the DBTP
• Number of participants with change from baseline in mean monthly average impact on everyday activities domain scores as measured by the MPFID [ Time Frame: Over Months 4, 5, and 6 of the double-blind treatment phase ]
  Change from baseline in mean monthly average impact on everyday activities domain scores as measured by the MPFID over months 4, 5, and 6 of the DBTP
• Number of participants with change from baseline in mean HIT-6 score [ Time Frame: Over Months 4, 5, and 6 of the double-blind treatment phase ]
  Change from baseline in mean HIT-6 score over months 4, 5, and 6 of the DBTP

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 chronic migraine (CM) population with medication overuse headache (MOH) and prior history of treatment failure. Subjects 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.

Subjects 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. Subjects who received erenumab treatment during the DBTP will continue to receive the same erenumab dose during the OLTP. Subjects 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 subjects will remain blinded to their original DBTP treatment assignment.

• Drug: Erenumab 70 mg
  Erenumab once every 4 weeks. Subcutaneous injection.
  Other Name: Aimovig
• Drug: Erenumab 140mg
  Erenumab once every 4 weeks. Subcutaneous injection.
  Other Name: Aimovig
• Drug: Placebo
  Placebo once every 4 weeks. Subcutaneous injection.

• Placebo Comparator: Placebo
  After subjects complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70mg or 140 mg) or placebo.
  Intervention: Drug: Placebo
• Active Comparator: Erenumab 70 mg
  After subjects 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.
  Intervention: Drug: Erenumab 70 mg
• Active Comparator: Erenumab 140 mg
  After subjects complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70mg or 140 mg) or placebo.
  Intervention: Drug: Erenumab 140mg

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, subjects 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. Subjects are eligible to be included in the study only if all of the following criteria apply:

• Subject 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

Subjects 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 preventative 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-CGRP 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 subject 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 enrolment 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 NSAIDs 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 subject 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 subject self-report, medical records or positivity on baseline pregnancy screening tests, through end of study