Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients
Condition: Episodic Migraine
MeSH terms: Migraine Disorders
Intervention: AMG334; Oral Prophylactic
Intervention description: Subcutaneous Injection; SOC Oral Tablet/Capsule
Intervention MeSH terms: Erenumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 621.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Erenumab; AMG334; Migraine; Episodic; Headache; CGRP

Summary:

      The purpose of this study is to compare the sustained long-term benefit between two treatment
      paradigms of migraine prophylactic agents (erenumab versus a control arm of oral
      prophylactics) in episodic migraine patients who have previously failed 1 to 2 prophylactic
      migraine treatments.
    

Eligibility criteria:

        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 12
             months prior to screening according to the International Classification of Headache
             Disorders-3rd Edition (ICHD-3).

          -  Greater than or equal to 4 and less than 15 days per month of migraine symptoms (based
             on ICHD-3 criteria) on average across 3 months prior to screening based on
             retrospective 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 treatments
             in the last 6 months due to either lack of efficacy or poor tolerability. For subjects
             with 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 have
             occurred 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 this
             study.

               -  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 7
                  medication categories for prophylactic treatment of migraine after an adequate
                  therapeutic 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 weeks
             at the generally accepted therapeutic dose(s) based on the investigator's assessment.

          -  Tolerability failure is defined as documented discontinuation due to adverse events of
             the 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 medications
             within 3 months prior to the start of and during baseline for a non-migraine
             indication 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 the
             start of the baseline period:

               -  Ergotamines or triptans on greater than or equal to 10 days per month, or Simple
                  analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on
                  greater than or equal to 15 days per month, or

               -  Opioid- or butalbital-containing analgesics on greater than or equal to 4 days
                  per month.

          -  Device, or procedure that potentially may interfere with the intensity or number of
             migraine days within 2 months prior to the start of or during baseline.

          -  History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or
             current evidence of depression. Subjects with anxiety disorder and/or major depressive
             disorders are permitted in the study if they are considered by the investigator to be
             stable and are taking no more than 1 medication for each disorder. Subjects must have
             been 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 than
             migraine. Note: a single childhood febrile seizure is not exclusionary.

          -  History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin or in situ cervical cancer), treated or untreated, within the past 5
             years, 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 condition
             or clinically significant vital sign, laboratory, or electrocardiogram (ECG)
             abnormality during that could pose a risk to subject safety or interfere with the
             study evaluation.

          -  Myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary
             artery bypass surgery or other re-vascularization procedures within 6 months prior to
             screening.

          -  Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if
             this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal
             Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also
             included in the Suicidal Behavior section), if this behavior occurred in the past 2
             years.

          -  Evidence of drug or alcohol abuse or dependence, based on Investigator discretion
             within 12 months.

          -  Pregnant or nursing (lactating) women.

          -  Women of child-bearing potential must use contraception during dosing with study
             treatment.

          -  Use of other investigational drugs within 5 half-lives of enrollment, or until the
             expected pharmacodynamic effect has returned to baseline, whichever is longer.

          -  History of hypersensitivity to any of the study drugs or its excipients or to drugs of
             similar chemical classes.

          -  Previous exposure to AMG334 or exposure to any other prophylactic CGRP-targeted
             therapy (prior to the study).