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

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 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 double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Population: Participants who received at least 1 dose of investigational product (IP) and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine days.

To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.

Time frame: CHU substudy day 29 (week 4) and day 57 (week 8)

Population: Participants enrolled in the CHU substudy who received at least 1 dose of investigational product in the substudy.

A migraine attack is an episode of any qualified migraine headache or migraine specific medication intakes for aura only. A migraine attack that was interrupted by sleep or that temporarily remits and then recurs within 48 hours or an attack treated successfully with medication but that relapses within 48 hours was considered to be one attack. The change from baseline in monthly migraine attacks was calculated as the number of migraine attacks during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine attacks during the 4-week baseline phase.

Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Population: Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine attacks.

AEs were graded using the CTCAE version 4.03: 1. Mild; asymptomatic or mild symptoms 2. Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities 3. Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care 4. Life-threatening consequences; urgent intervention indicated 5. Death related to AE A serious adverse event is an AE that meets at least 1 of the following criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event An adverse device effect is any AE related to the use of a medical device, including AEs resulting from insufficient or inadequate instructions for use, any malfunction of the device, or use error or from intentional misuse of the device.

Time frame: From first dose in the CHU substudy to end of substudy (up to 12 weeks)

Population: Participants enrolled in the CHU substudy who received at least 1 dose of investigational product in the substudy.

Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative or had no result at baseline but positive at any time postbaseline during the DBTP. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

Time frame: 12 weeks

Population: Participants who received at least 1 dose of IP and with valid postbaseline antibody testing results.

Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. Participants who developed anti-erenumab antibodies are participants who were negative prior to the first OLTP dose but positive at any time during the OLTP, or participants with no data prior to first dose in OLTP with any post-baseline positive results. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.

Time frame: From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.

Population: Participants who received at least 1 dose of IP in the OLTP and with valid antibody testing results during the OLTP.

An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: 1. Mild; asymptomatic or mild symptoms 2. Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities 3. Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care 4. Life-threatening consequences; urgent intervention indicated 5. Death related to AE A serious adverse event is an AE that meets at least 1 of the following criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event

Time frame: From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase.

Population: Randomized participants who received at least one dose of investigational product (safety analysis set).

An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: 1. Mild; asymptomatic or mild symptoms 2. Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities 3. Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care 4. Life-threatening consequences; urgent intervention indicated 5. Death related to AE A serious adverse event is an AE that meets at least 1 of the following criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event

Time frame: From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.

Population: All participants who received at least one dose of investigational product in the open-label treatment phase (open-label treatment phase set).

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 double-blind 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 double-blind treatment phase \* 100 / baseline monthly migraine days was less than or equal to -50%.

Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

Population: Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set) with available data at week 12.