A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.

A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.

This was a multicenter, 52-week, open-label study designed to assess the long-term safety and efficacy of erenumab in adults with chronic migraine. Participants who completed the 12-week double-blind treatment of the parent Study 20120295 (NCT02066415) and met all Study 20130255 eligibility criteria were eligible for enrollment into this study. Enrollment occurred within 14 days after the parent study's week 12 visit. The initial dose used in the study was erenumab 70 mg every month (QM). The protocol was subsequently amended to increase the dose to erenumab 140 mg QM (Protocol Amendment 2). Participants who had already completed the week 28 visit (ie, midpoint of the study) at the time of Protocol Amendment 2 continued to receive open-label erenumab 70 mg QM for the remainder of the study. Participants who enrolled but had not completed the week 28 visit at the time of Protocol Amendment 2 increased the open-label erenumab dose from 70 mg QM to 140 mg QM at the next visit. All participants who enrolled after Protocol Amendment 2 received open-label erenumab 140 mg QM throughout the study. Participants may elect to participate in a separate clinical home use (CHU) substudy to assess subjects' ability to self-administer 140 mg of erenumab for in-home use using either two prefilled syringes (PFS) or two prefilled autoinjector/pens (AI/pens). Enrollment in the 12-week substudy occurred at either week 12 or week 40 of study 20130255. Participants were randomized to self-administer erenumab using either the PFS or AI/pen on CHU days 29 and 57 at home.

Participants received erenumab 70 mg once a month (QM) or 140 mg QM by subcutaneous injection for up to 52 weeks.

Adverse events (AEs) were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate AE; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; urgent intervention indicated; Grade 5 = Death related to AE.

From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).

At the CHU substudy day 28 and day 56 visits, the site provided erenumab 140 mg to participants to self-administer at home on the following day. Study site staff then called the participants and asked if they administered a full, partial, or no dose of erenumab. A full dose was defined when the entire volume of both prefilled syringes or autoinjector/pens were injected.

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the 4 weeks prior to each study visit - the number of migraine days during the 4-week baseline phase.

4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255

Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the 4 weeks prior to each study visit. At least a 50% reduction from baseline (of study 20120295) in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the 4 weeks prior to each study visit * 100 / baseline monthly migraine days was less than or equal to -50%.

4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255

The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or a headache of any duration for which acute headache treatment was administered.

4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255

Adverse events were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Injection site reactions were derived from a Medical Dictionary for Regulatory Activities (MedDRA) query using a list of pre-specified preferred terms. An adverse device effect (ADE) is any adverse event related to the use of a medical device.

From first dose of erenumab in the CHU substudy to 28 days after last dose of erenumab in the CHU substudy; up to 12 weeks.

Inclusion Criteria: Subject has provided informed consent prior to initiation of any study-specific activities/procedures Completed the 12-week study visit and did not end IP early during the double-blind treatment period of the AMG 334 20120295 (NCT02066415) parent study, and is appropriate for continued treatment. Exclusion Criteria: Development of any unstable or clinically significant medical condition, laboratory or electrocardiogram (ECG) abnormality following randomization into the parent study, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. Systolic blood pressure (BP) 160 mm Hg and/or diastolic BP 100 mm Hg or greater at screening/Day 1. Subject who used excluded concomitant medications between week 8 and week 12 of the parent study

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