Imaging the Migraine Brain Pre- and Post-Erenumab

The study will include 50 participants with migraine aged 18-65 years who have 10-25 migraine
days per month at baseline. Following a 4-week headache diary run-in phase, participants will
receive two treatments with once monthly subcutaneous injections of erenumab 140 mg.
Questionnaires, structured interviews, cognitive tests, quantitative sensory testing and
brain imaging will be performed prior to and following erenumab treatment. These data will be
collected at early time points after the first treatment as well as at eight weeks following
the first treatment to allow for identification of early and late effects of erenumab on
clinical, physiologic, and imaging outcomes and to determine if early physiologic and imaging
outcomes predict clinical outcomes at eight weeks. Physiologic and imaging data will be
compared to already collected data from healthy controls so as to interpret changes that are
seen following treatment with erenumab.

Inclusion Criteria

- 18-65 years of age

- Episodic migraine (with or without aura) or chronic migraine according to the
diagnostic criteria included within the International Classification of Headache
Disorders 3 (ICHD-3)

- 10-25 migraine days per month on average over the 3 months prior to screening,
confirmed by run-in phase prospective data collection

- Duration since migraine onset of at least 12 months prior to screening based on
medical records and/or patient self-report

Exclusion Criteria

- Older than 50 years of age at migraine onset

- History of cluster headache or hemiplegic migraine

- Continuous headache pain (i.e. no pain-free periods of any duration during the one
month before screening)

- Opioid- or butalbital-containing analgesics on 6 or more days per month during the 2
months prior to the start of the baseline phase

- History of major psychiatric disorder such as schizophrenia and bipolar disorder

- History or evidence of any unstable or clinically significant medical condition, that
in the opinion of the investigator, would pose a risk to subject safety or interfere
with the study evaluation, procedures, or completion

- No therapeutic response in migraine prevention after an adequate therapeutic trial of
4 or more of the following medication categories: Category 1- divalproex sodium,
sodium valproate; Category 2- topiramate; Category 3- beta-blockers; Category 4-
tricyclic antidepressants; Category 5- venlafaxine or desvenlafaxine, duloxetine or
milnacipran; Category 6- flunarizine, verapamil; Category 7- lisinopril, candesartan;
Category 8- botulinum toxin. No therapeutic response is defined as no reduction in
headache frequency, duration, 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. Lack of sustained response to a medication and failure to
tolerate a therapeutic dose are not considered to be "no therapeutic response".

- Concomitant use of 3 or more of the following medications for migraine prevention
within 2 months before the start of the baseline phase or throughout the study:
divalproex sodium, sodium valproate, topiramate, carbamazepine, gabapentin,
beta-blockers, tricyclic antidepressants, venlafaxine, desvenlafaxine, duloxetine,
milnacipran, flunarizine, verapamil, lomerizine, lisinopril, candesartan, clonidine,
guanfacine, cyproheptadine, methysergide, pizotifen, butterbur, feverfew, magnesium
(at least 600 mg per day), riboflavin (at least 100 mg per day). Use of up to two
medications is permitted as long as the dose has been stable for at least 2 months
before the start of the run-in phase and during the study.

- Botulinum toxin (in the head and/or neck region) within 4 months before the start of
the baseline phase and throughout the study

- Ergotamine derivatives, steroids, and triptans used for migraine prophylaxis within 2
months before the start of the baseline phase and throughout the study

- Procedures (e.g. nerve blocks) used for migraine prophylaxis within 2 months before
the start of the baseline phase and throughout the study

- History of myocardial infarction, stroke, transient ischemic attack, unstable angina,
coronary artery bypass surgery, or other revascularization procedures within 12 months
prior to screening.

- Contraindications to MRI including, but not limited to: Metal implants, aneurysm
clips, severe claustrophobia, implanted electronic devices, insulin or infusion pump,
cochlear/otologic/ear implant, non-removable prosthesis, implanted shunts/catheters,
certain intrauterine devices, tattooed makeup, body piercings that cannot be removed,
metal fragments, wire sutures or metal staples.

- Factors that Reduce MR Image Quality and Interpretability: dental braces or other
non-removable devices (e.g. retainers); prior brain surgery; known brain MRI
abnormality that in the investigator's opinion will significantly impact MRI data

- Sensory disorders that in the investigator's opinion might affect perception of
cutaneous thermal stimuli (e.g. peripheral neuropathy)

- Pregnancy

- Lactation

- Not willing to use a reliable form of contraception (for women of childbearing
potential) through 16 weeks after the last dose of erenumab. Acceptable methods of
birth control include not having intercourse, hormonal birth control methods,
intrauterine devices, surgical contraceptive methods, or two barrier methods (each
partner must use a barrier method) with spermicide. A reliable form of contraception
must be started prior to or at the time of starting the run-in phase. Not being of
childbearing potential is defined as any woman who: 1) is post-menopausal by history,
defined as: a) At least 55 years of age with cessation of menses for 12 or more
months, OR b) Younger than 55 years of age but no spontaneous menses for at least 2
years, OR c)Younger than 55 years of age and spontaneous menses within the past 1
year, but currently amenorrheic (e.g. spontaneous or secondary to hysterectomy), AND
with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating
hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL)
or according to the definition of "postmenopausal range" for the laboratory involved,
OR d) Underwent bilateral oophorectomy, OR e) Underwent hysterectomy, OR f) Underwent
bilateral salpingectomy

- Currently receiving treatment in another drug study or an investigational device
study, or less than 90 days prior to screening since ending treatment on another
investigational device or drug study(-ies)

- Has received CGRP monoclonal antibody within 4 months of the start of the run-in phase

- Active chronic pain condition that in the investigator's opinion is unrelated to
migraine (e.g. chronic pelvic pain)

- Acute pain condition that in the investigator's opinion is unrelated to migraine (e.g.
post-surgical pain)

- Unable to provide informed consent

- Less than 80% compliance with providing headache diary data during the run-in phase
(i.e. provides data on less than 80% of days)