A Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Chronic Migraine Prevention

Phase 2

Completed

Conditions: Treatment for Prevention of Chronic Migraine

Interventions: Drug: Placebo
Biological: Erenumab

Registration Number: NCT02066415

Lead Sponsor: Amgen

Brief Summary: To evaluate the effect of erenumab compared to placebo on the change from baseline in the number of monthly migraine days in adults with chronic migraine.

Detailed Description: This study consisted of the following phases: screening, 4-week baseline phase, 12-week double-blind treatment, and 12-week follow-up. Participants may have elected to participate in the optional pharmacokinetic substudy and the optional, novel patient-reported outcome (PRO) assessment substudy.

Participants who completed the 12-week double-blind treatment phase of Study 20120295 were eligible to enroll in an open-label extension study (Study 20130255; NCT02174861).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 667

Inclusion Criteria

History of at least 5 attacks of migraine without aura and/or migraine with visual sensory, speech and/or language, retinal or brainstem aura.
History of ≥ 15 headache days per month of which ≥ 8 headache days were assessed by the subject as migraine day.
≥ 4 distinct headache episodes, each lasting ≥ 4 hours OR if shorter, associated with use of a triptan or ergot-derivative on the same calendar day based on the eDiary calculations.
Demonstrated at least 80% compliance with the eDiary.

Exclusion Criteria

History of cluster headache or hemiplegic migraine headache
Unable to differentiate migraine from other headaches
Failed > 3 medication categories due to lack of efficacy for prophylactic treatment of migraine .
Received botulinum toxinin head or neck region within 4 months prior to screening.
Used a prohibited migraine prophylactic medication, device or procedure within 2 months prior to the start of the baseline phase

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection.
Erenumab 70 mg	Erenumab	Participants received 70 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.
Erenumab 140 mg	Erenumab	Participants received 140 mg erenumab on day 1 and at weeks 4 and 8 by subcutaneous injection.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Monthly Migraine Days	4-week baseline phase and the last 4 weeks of the 12-week treatment phase	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 last 4 weeks of the 12-week treatment phase - the number of migraine days during the 4-week baseline phase.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Baseline	4-week baseline phase and the last 4 weeks of the 12-week treatment phase	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 last 4 weeks of treatment. At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 4 weeks of the 12-week treatment phase \* 100 / baseline monthly migraine days was less than or equal to -50%.
Number of Participants With Adverse Events	From the first dose of study drug up to 16 weeks after the last dose (24 weeks)	Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.
Number of Participants Who Developed Antibodies to Erenumab	Baseline and weeks 2, 4, 8, 12 and 24	Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.
Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days	4-week baseline phase and the last 4 weeks of the 12-week treatment phase	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.
Change From Baseline in Cumulative Monthly Headache Hours	4-week baseline phase and the last 4 weeks of the 12-week treatment phase	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.