A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache
Condition: Migraine Headache
MeSH terms: Migraine Disorders; Headache Disorders, Secondary; Headache
Intervention: Erenumab 70 mg; Erenumab 140 mg; Placebo
Intervention description: Erenumab once every 4 weeks. Subcutaneous injection.; Erenumab once every 4 weeks. Subcutaneous injection.; Placebo once every 4 weeks. Subcutaneous injection.
Intervention MeSH terms: Erenumab; Antibodies, Monoclonal
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 620.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Chronic Migraine; Medication Overuse Headache

Summary:

      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).
    

Eligibility criteria:

        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