A Prospective Interventional Study of Intranasal Zavegepant for the Acute Treatment of Migraine

This is a prospective, multicenter, interventional study conducted in a real-world setting, enrolling adult participants receiving zavegepant for the acute treatment of migraine. The study is classified as interventional due to the requirement for participants to complete protocol-mandated questionnaires and a patient diary. No protocol-specified therapeutic or diagnostic interventions are required. Participants management will otherwise follow routine clinical practice, and participants will receive study medication at no cost. Recruitment is planned from September 2026 through September 30, 2027. The index date is defined as the date on which the participant signs the Informed Consent Document (ICD). Eligible participants will receive a supply of study medication (up to 54 doses) at the index date. Additional medication may be provided at the investigator's discretion for participants with a higher frequency of migraine attacks, in accordance with study procedures.

Each participant will be followed for approximately 4 months, including a 3-month treatment period and a 1-month follow-up period. Approximately 250 adult participants are planned for enrollment.Collected data will include demographics, migraine history, substance use, patient-reported headache episodes recorded in a paper diary, and patient-reported outcomes (PROs) documented in case report forms (CRFs). PRO assessments will be completed during on-site visits.

Treatment Initiation: At the start of the treatment period, a one-week washout period is required prior to the first dose of zavegepant. During this period, participants should not use any acute migraine medications; however, short-acting triptans may be used as rescue medication if needed. Long-acting triptans (e.g., naratriptan and frovatriptan) must not be used. Participants without migraine attacks during the washout period may initiate treatment at their next migraine attack. Any ongoing preventive migraine treatments should remain stable throughout the washout period and the entire three-month treatment period. Treatment Administration and Migraine Attack Management: For the first three evaluable migraine attacks treated during the study, participants are required to complete the patient diary as described in section related to Patient Diary. Zavegepant should be administered only when the migraine headache reaches a moderate to severe level of pain. No other acute migraine medication should be taken prior to zavegepant administration. Rescue medication may be used if needed, but only ≥2 hours after dosing with zavegepant. For subsequent migraine attacks, participants may administer zavegepant at any time they consider appropriate, regardless of headache pain intensity or stage, including during mild pain or the prodromal phase (i.e., early symptoms indicating the onset of a migraine attack).

At Visit 1, participants will be dispensed a total of 54 doses of zavegepant, corresponding to a planned supply of 18 doses per month. This quantity is expected, in general, to cover treatment needs for the duration of the study. If a participant requires more than 18 doses within a given month, the Co-Investigator should notify the Principal Investigator to arrange additional supply in accordance with study procedures.

The primary assessment of effectiveness will focus on the first treated migraine attack, based on pain relief at 2 hours post dose.

Secondary assessments will also include additional measures of effectiveness, including pain freedom, absence of the most bothersome symptom (MBS), resolution of associated symptoms, sustained pain response, return to normal function, and use of rescue medication.

Effectiveness will be evaluated using patient-reported outcomes, including changes from Visit 1 to Visit 4 in headache impact (HIT-6), migraine-related disability (MIDAS), work productivity (WPAI: Migraine 2.0), and mood-related symptoms (PHQ-4 and GAD-7), as well as overall treatment improvement assessed by PGI-I at Visit 4.

Exploratory assessments will include early treatment response (up to 60 minutes post-dose), consistency of treatment effect across multiple attacks, and time to meaningful pain relief for the first treated attack. Analyses may include up to the first three evaluable migraine attacks treated with zavegepant, with a minimum 48-hour interval between treated attacks.

Rescue medication is defined as the use of any additional acute migraine treatment following zavegepant administration to manage insufficient symptom relief.

All analyses will be based on observed data; missing data will not be imputed. Denominators will be defined per endpoint. All study assessments are consistent with routine clinical practice or standard care for the target population.