study of sustained benefit of amg334 in adult episodic migraine patients

Conditions: Episodic Migraine

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).

Keywords: erenumab amg334 migraine episodic headache cgrp