Fremanezumab Treatment of Migraine in Women With Menstrual Migraine Ages 18-45

Inclusion Criteria:

Patients may be randomized in this study only if they meet all of the following criteria:

1. The patient is capable of giving signed informed consent, which includes compliancewith the requirements and restrictions listed in this protocol

2. The patient is female aged 18 to 45 years of age, inclusive

3. The patient has a diagnosis of pure menstrual migraine (MM) or menstrual-relatedmigraine (MRM)

4. Prior to the screening visit (V1) the patient has a 6 month history of either:

• Menstrual Migraine (MM)

• Headache consistent with Menstrual Migraine (MM)

• Menstrually-Related Migraine (MRM)

5. The patient fulfils the following criteria for migraine in a prospectively collecteddiary during the 28-day baseline period:

○ Migraine attacks starting in the peri-menstrual period (days -2 to +3 ofmenstruation) AND

• Pure Menstrual migraine with aura, either/or

• Menstrually-related migraine with aura, either/or

• Pure Menstrual migraine without aura, either/or

• Menstrually-related migraine without aura

6. The patient agrees not to initiate any migraine preventive medications during thestudy

7. The patient is in good health in the opinion of the sponsor as determined by medicalevaluation, including medical history, neurologic examination, laboratory tests andcardiac monitoring

8. The patient has a body weight ≥45 kg and a body mass index within the range of 17.5to 34.9 kg/m^2, inclusive

9. The patient demonstrated compliance with the electronic headache diary during the 28-day baseline period by entry of headache data on a minimum of 21 days cumulativeduring the 28-day baseline period (~diary compliance)

10. Three months of regular menstrual cycle prior to baseline period and 1 regular cycle (within 21-28 days) of previous cycle during the baseline run-in period

11. Patients not using birth control must have a negative urine beta-human chorionicgonadotrophin(β-HCG) test at the Screening Visit (V1), and must not be in a sexualrelationship with a person who produces sperm or must be medically confirmed assterile. These conditions must be met from the baseline period through the entireduration of study and 5.5 months after the last dose of fremanezumab.

12. Patients using birth control must have a negative β-HCG test result and practice ahighly effective method of birth control prior to treatment administration and 5.5months following the last dose of IMP. Birth control permitted should allow estrogendrop and maintenance of monthly cycle: estrogen/progesterone pills;etonogestrel/ethinylestradiol ring; copper intrauterine device (IUD) andprogesterone-containing IUD and have been on their current birth control for ≥30days.

13. The patient must be willing and able to comply with study restrictions and attendthe clinic for all study visits required for the duration of the study and to attendfollow up evaluations, as specified in the protocol

Exclusion Criteria:

Patients will not be randomized/enrolled in this study if they meet any of the following criteria:

1. The patient uses medications containing opioids or barbiturates on more than 4 daysduring the 28-day baseline period for the treatment of migraine or any other reason

2. The patient uses >8 rimegepant or ubrogepant tablets per month

3. The patient has ≥15 headache days per month

4. The patient has used am intervention/device (eg, scheduled nerve blocks, implantablevagal nerve stimulation, and transcranial magnetic stimulation) for migraine duringthe 2 months prior to screening

5. The patient is overusing acute medication

6. The patient is pregnant or lactating or planning to get pregnant in ≤13 months postscreening visit (V1)

7. The patient has clinically significant hematological, cardiac, renal, endocrine,pulmonary, gastrointestinal, genitourinary, neurologic, hepatic or ocular disease,at the discretion of the sponsor

8. The patient has a history of clinically significant cardiovascular disease orvascular ischemia (such as myocardial, neurological [eg, cerebral ischemia],peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events), such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism

9. The patient has a known infection or history of human immunodeficiency virus,tuberculosis, any history of Lyme disease, or chronic hepatitis B or C infection

10. The patient has a past or current history of cancer, except for appropriatelytreated non-melanoma skin carcinoma

11. The patient has a history of hypersensitivity reactions to injected proteins,including monoclonal antibodies

12. The patient has participated in a clinical study of a new chemical entity or aprescription medicine within 2 months of the screening visit (V1) or 3 months incase of biologics if the half-life of the biologics is unknown or 5 half-lives,whichever is longer, or is currently participating in another study of an IMP (or amedical device)

13. The patient has previously received treatment with any calcitonin generelatedpeptide pathway (ligand/receptor) target therapy(erenumab, eptinezumab,galcanezumab, fremanezumab, rimegepant 75 mg every other day, or atogepant) or isactively taking them during the study

14. The patient has any finding in the baseline 12-lead electrocardiogram consideredclinically significant in the judgment of the sponsor

15. The patient has any finding that, in the judgment of the sponsor, is a clinicallysignificant abnormality, including serum chemistry, hematology, coagulation, andurinalysis test values (abnormal tests may be repeated for confirmation)

16. The patient has a prior medical history of hepatic enzymes (alanineaminotransferase, aspartate aminotransferase, and alkaline phosphatase) >1.5x theupper limit of the normal range or suspected hepatocellular damage that fulfills thecriteria for Hy's law during their prior medical history review at screening visit.

17. The patient has a prior medical history of significant proteinuria or evidence ofrenal disease at the Screening Visit (V1).

18. The patient has any clinically significant uncontrolled medical condition (treatedor untreated). The patient has a history of alcohol or drug abuse in the opinion ofthe sponsor

19. The patient cannot participate or successfully complete the study, in the opinion oftheir healthcare provider or the sponsor, for any of the following reasons:

• mentally or legally incapacitated or unable to give consent for any reason

• in custody due to an administrative or a legal decision, under tutelage, orbeing admitted to a sanitarium or social institution

• unable to be contacted in case of emergency

• has any other condition, which, in the opinion of the sponsor, makes thepatient in appropriate for inclusion in the study

20. The patient is an employee who is directly involved in the study or the relative ofsuch an employee

21. The patient has any disorder that may interfere with the absorption, distribution,metabolism, or excretion of IMP

22. The patient is vulnerable (eg, people kept in detention)

23. The patient has previously participated in this study