MR-Spectroscopy: Investigating neurochemical changes in brain metabolism in migraineurs before and after CGRP-Antibody treatment – a randomized, controlled, open-label trial.

Prior treatment

• Previous exposure to Fremanezumab 225mg monthly or 675mg quarterly or exposure to any other prophylactic CGRP-targeted therapy (prior to and during the study)
• Exposure to botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline period, during the baseline period, or treatment period
• Traditional medications and/or procedures are not allowed if not used at a stable dose/frequency for at least 3 months prior to randomization and during the study
• Taken the following for any indication during 2 months prior to screening: -Ergotamines or triptans on ≥10 days per month, or -NSAIDs, acetaminophen on ≥15 days per month, or -Opioid-containing analgesics on ≥4 days per month
• Evidence of drug or alcohol abuse or dependence in the past, based on medical records, patient self-report
• Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer

Other illness

• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
• History of cluster headache or hemiplegic migraine headache
• Active chronic pain syndromes (e.g., fibromyalgia, chronic pelvic pain)
• History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or current evidence of depression
• History of seizure disorder or other significant neurological conditions other than migraine
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years
• Human immunodeficiency virus (HIV) infection by history
• History or evidence of any other unstable or clinically significant medical condition
• Coronary artery disease, myocardial infarction, stroke, transient ischemic attack, stable or unstable angina pectoris, carotid or vertebro-basilar artery disease, other cerebrovascular conditions (e.g.: AV malformation, aneurysm)

Age

• Older than 50 years of age at migraine onset

Other

• Unable to differentiate migraine from other headaches
• Unlikely to be able to complete all protocol required study procedures to the best of the subject’s and investigator’s knowledge
• Subject has any clinically significant vital sign during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing with study treatment

• Written informed consent must be obtained before assessment is performed
• Adults > 18 and < 65 of age upon entry into screening
• Documented history of migraine with or without aura > 12 months prior to screening according to the International Classification of Headache Disorders - 3rd Edition (ICHD-3)
• Migraine frequency ≥ 4 and ≤ 15 migraine days per month across the 3 months prior to screening based on retrospective reporting
• Subject has not received a CGRP mAB for migraine prophylaxis in the past
• Subject can differentiate migraine from other headaches
• Lack of contraindication for MRI