Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Adults greater than or equal to 18 years of age upon entry into screening.
• Documented history of migraine (with or without aura) greater than or equal to 12months prior to screening according to the International Classification of HeadacheDisorders-3rd Edition (ICHD-3).
• Greater than or equal to 4 and less than 15 days per month of migraine symptoms (basedon ICHD-3 criteria) on average across 3 months prior to screening based onretrospective reporting.
• Less than 15 days per month of headache symptoms (i.e., migraine and non-migraine).
• Subjects in need for switching by documented failure of 1 or 2 prophylactic treatmentsin the last 6 months due to either lack of efficacy or poor tolerability. For subjectswith 1 prior treatment failure, the failure should have occurred in the last 6 months.For subjects with 2 prior treatment failures, the second treatment failure should haveoccurred in the last 6 months.
• During baseline: Confirmed migraine frequency of 4 to 14 migraine days and less than 15 days of headache symptoms.
• During baseline: greater than or equal to 80% compliance with the headache diary.

Exclusion Criteria:

• Subjects meeting any of the following criteria are not eligible for inclusion in thisstudy.
• Older than 50 years of age at migraine onset.
• History of cluster headache or hemiplegic migraine headache.
• Unable to differentiate migraine from other headaches.
• Lack of efficacy or poor tolerability with greater than 2 treatments from the 7medication categories for prophylactic treatment of migraine after an adequatetherapeutic trial.
• Efficacy failure is defined as no meaningful reduction in headache frequency,duration, and/or severity after administration of the medication for at least 6 weeksat the generally accepted therapeutic dose(s) based on the investigator's assessment.
• Tolerability failure is defined as documented discontinuation due to adverse events ofthe respective medication during the last 6 months prior to screening.
• The following scenarios do not constitute lack of therapeutic response:
• Lack of sustained response to a medication.
• Patient decision to halt treatment due to improvement.
• Used a prohibited medication from the 7 categories of prior prophylactic medicationswithin 3 months prior to the start of and during baseline for a non-migraineindication if dose is not stable
• Exposure to botulinum toxin in the head and/or neck region within 4 months.
• Taken the following for any indication in any month during the 2 months prior to thestart of the baseline period:
• Ergotamines or triptans on greater than or equal to 10 days per month, or Simpleanalgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) ongreater than or equal to 15 days per month, or
• Opioid- or butalbital-containing analgesics on greater than or equal to 4 daysper month.
• Device, or procedure that potentially may interfere with the intensity or number ofmigraine days within 2 months prior to the start of or during baseline.
• History of major psychiatric disorders (such as schizophrenia or bipolar disorder) orcurrent evidence of depression. Subjects with anxiety disorder and/or major depressivedisorders are permitted in the study if they are considered by the investigator to bestable and are taking no more than 1 medication for each disorder. Subjects must havebeen on a stable dose within the 3 months prior to the start of the baseline period.
• History of seizure disorder or other significant neurological conditions other thanmigraine. Note: a single childhood febrile seizure is not exclusionary.
• History of malignancy of any organ system (other than localized basal cell carcinomaof the skin or in situ cervical cancer), treated or untreated, within the past 5years, regardless of whether there is evidence of local recurrence or metastases.
• Human immunodeficiency virus (HIV) infection by history.
• History or evidence of any other unstable or clinically significant medical conditionor clinically significant vital sign, laboratory, or electrocardiogram (ECG)abnormality during that could pose a risk to subject safety or interfere with thestudy evaluation.
• Myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronaryartery bypass surgery or other re-vascularization procedures within 6 months prior toscreening.
• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, ifthis ideation occurred in the past 6 months, or "yes" on any item of the SuicidalBehavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item alsoincluded in the Suicidal Behavior section), if this behavior occurred in the past 2years.
• Evidence of drug or alcohol abuse or dependence, based on Investigator discretionwithin 12 months.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential must use contraception during dosing with studytreatment.
• Use of other investigational drugs within 5 half-lives of enrollment, or until theexpected pharmacodynamic effect has returned to baseline, whichever is longer.
• History of hypersensitivity to any of the study drugs or its excipients or to drugs ofsimilar chemical classes.
• Previous exposure to AMG334 or exposure to any other prophylactic CGRP-targetedtherapy (prior to the study).