Treatment for Prevention of Chronic Migraine
Conditions
Keywords
Chronic Migraine
Brief summary
To assess the long-term safety and efficacy of erenumab.
Detailed description
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.
Interventions
DRUGErenumab
Administered by subcutaneous injection once a month
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has provided informed consent prior to initiation of any study-specific activities/procedures 2. 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
1. 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. 2. Systolic blood pressure (BP) 160 mm Hg and/or diastolic BP 100 mm Hg or greater at screening/Day 1. 3. Subject who used excluded concomitant medications between week 8 and week 12 of the parent study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 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. |
| CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use | Day 29 (week 4) and day 57 (week 8) of the substudy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | 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. |
| Change From Study 20120295 Baseline in Monthly Migraine Days | 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 | 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. |
| CHU Substudy: Number of Participants With Adverse Events | 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. | 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. |
| Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | 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. |
| Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | 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 | 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%. |
Countries
Canada, Czechia, Denmark, Finland, Germany, Norway, Poland, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 64 centers across North America and Europe from 30 June 2014 to 4 March 2016. 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.
Pre-assignment details
Participants at sites in the United States, Sweden, and Germany had the option of enrolling in the Clinical Home Use (CHU) Substudy to assess their ability to self-administer 140 mg erenumab for in-home use. Participants in the substudy were randomized 1:1 to self-administer erenumab using either a prefilled syringe or autoinjector/pen.
Participants by arm
| Arm | Count |
|---|---|
| Erenumab Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.
Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study. | 609 |
| Total | 609 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Decision by sponsor | 8 |
| Overall Study | Lost to Follow-up | 26 |
| Overall Study | Withdrawal by Subject | 124 |
Baseline characteristics
| Characteristic | Erenumab |
|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 11.3 |
| Age, Customized 18 - 64 years | 608 Participants |
| Age, Customized 65 - 74 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 584 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 25 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized White | 574 Participants |
| Sex: Female, Male Female | 509 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 609 |
| other Total, other adverse events | 162 / 609 |
| serious Total, serious adverse events | 24 / 609 |
Outcome results
Primary
CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use
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.
Time frame: Day 29 (week 4) and day 57 (week 8) of the substudy
Population: All randomized participants who received at least 1 dose of erenumab in the CHU substudy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab | CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use | Week 4 | 25 Participants |
| Erenumab | CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use | Week 8 | 25 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use | Week 4 | 26 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use | Week 8 | 25 Participants |
Primary
Number of Participants With Adverse Events
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.
Time frame: From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).
Population: All enrolled participants who received at least 1 dose of erenumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab | Number of Participants With Adverse Events | Adverse event grade ≥ 2 | 302 Participants |
| Erenumab | Number of Participants With Adverse Events | Adverse event grade ≥ 3 | 34 Participants |
| Erenumab | Number of Participants With Adverse Events | Adverse event grade ≥ 4 | 0 Participants |
| Erenumab | Number of Participants With Adverse Events | Any adverse event | 398 Participants |
| Erenumab | Number of Participants With Adverse Events | Treatment-related adverse events | 114 Participants |
| Erenumab | Number of Participants With Adverse Events | Serious adverse events | 24 Participants |
| Erenumab | Number of Participants With Adverse Events | AE leading to discontinuation of erenumab | 16 Participants |
| Erenumab | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
Secondary
Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours
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.
Time frame: 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
Population: Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Baseline | 226.84 hours / month | Standard Deviation 125.54 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from baseline at week 4 | -79.38 hours / month | Standard Deviation 107.56 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from baseline at week 8 | -85.24 hours / month | Standard Deviation 110.24 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from Baseline at week 12 | -89.30 hours / month | Standard Deviation 111.47 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from Baseline at week 24 | -100.41 hours / month | Standard Deviation 112.3 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from Baseline at week 40 | -101.07 hours / month | Standard Deviation 111.77 |
| Erenumab | Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | Change from Baseline at week 52 | -107.44 hours / month | Standard Deviation 113.6 |
Secondary
Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days
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.
Time frame: 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
Population: Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Baseline | 9.53 acute migraine treatment days / month | Standard Deviation 7.26 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 4 | -3.59 acute migraine treatment days / month | Standard Deviation 4.62 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 8 | -4.01 acute migraine treatment days / month | Standard Deviation 4.96 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 12 | -3.96 acute migraine treatment days / month | Standard Deviation 5.03 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 24 | -4.39 acute migraine treatment days / month | Standard Deviation 4.99 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 40 | -4.58 acute migraine treatment days / month | Standard Deviation 5 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | Change from baseline at Week 52 | -4.97 acute migraine treatment days / month | Standard Deviation 5.33 |
Secondary
Change From Study 20120295 Baseline in Monthly Migraine Days
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.
Time frame: 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
Population: Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The number of participants analyzed includes participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Baseline | 18.11 migraine days / month | Standard Deviation 4.53 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 4 | -6.72 migraine days / month | Standard Deviation 6.22 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 8 | -7.38 migraine days / month | Standard Deviation 6.5 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 12 | -7.63 migraine days / month | Standard Deviation 6.49 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 24 | -8.36 migraine days / month | Standard Deviation 6.29 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 40 | -8.72 migraine days / month | Standard Deviation 6.53 |
| Erenumab | Change From Study 20120295 Baseline in Monthly Migraine Days | Change from baseline at week 52 | -9.29 migraine days / month | Standard Deviation 6.64 |
Secondary
CHU Substudy: Number of Participants With Adverse Events
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.
Time frame: 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.
Population: All randomized participants who received at least one dose of erenumab in the CHU substudy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 2 | 1 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | AE leading to discontinuation of erenumab | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 4 | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 3 | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Injection site reactions | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Adverse device effects | 0 Participants |
| Erenumab | CHU Substudy: Number of Participants With Adverse Events | Any adverse event | 2 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Adverse device effects | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Any adverse event | 6 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 2 | 4 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 3 | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Adverse event grade ≥ 4 | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | AE leading to discontinuation of erenumab | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Erenumab 140 mg AI/Pen | CHU Substudy: Number of Participants With Adverse Events | Injection site reactions | 1 Participants |
Secondary
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%.
Time frame: 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
Population: Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 4 | 39.2 percentage of participants |
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 8 | 45.6 percentage of participants |
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 12 | 45.7 percentage of participants |
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 24 | 53.6 percentage of participants |
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 40 | 55.6 percentage of participants |
| Erenumab | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | Week 52 | 59.0 percentage of participants |