The main goal of this trial is to learn whether eptinezumab improves migraine symptoms and quality of life of participants with migraine who did not perceive a sufficient improvement during previous treatment with therapies targeting calcitonin gene-related peptide (CGRP).

Key Inclusion Criteria:

• The participant has a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders 3rd Edition (ICHD-3) guidelines with a history of migraine of at least 12 months prior to the Screening Visit.
• The participant has ≥8 migraine days per month for each month within the past 3 months prior to the Screening Visit.
• The participant has documented evidence of recent inadequate response to either one anti-CGRP monoclonal antibody (mAb) (other than eptinezumab) or one gepant, indicated and used for migraine prevention.

Key Exclusion Criteria:

• The participant has taken more than 10 tablets of ubrogepant or more than 8 tablets of rimegepant per month as an acute migraine medication in the 1 month prior to the screening visit and during the 4-week baseline period.
• The participant has previously had an inadequate response to more than one CGRP-targeting therapy (anti-CGRP mAb or gepants), indicated for migraine prevention.
• The participant has a history of cancer, other than basal cell or stage 1 squamous cell carcinoma of the skin or adequately treated cervical intraepithelial neoplasia, that has not been in remission for >5 years prior to the first dose of eptinezumab. Male participants with abnormal prostate-specific antigen levels according to national/local guideline may be enrolled in the trial provided they have been followed up, have been asymptomatic, and have had no treatment for prostate cancer. Participants under surveillance for a low and stable level of M-component are allowed.
• The participant has previously been treated with eptinezumab.

Other protocol-defined inclusion and exclusion criteria apply.