Abstract
OBJECTIVE: The primary objective was to characterize the pharmacokinetics (PK) and safety of eptinezumab in children and adolescents with migraine. BACKGROUND: Migraine in children and adolescents is a prevalent and potentially debilitating disease, and few preventive therapies are approved for use in these populations. Eptinezumab, a calcitonin gene-related peptide monoclonal antibody approved for migraine prevention in adults, has demonstrated efficacy at doses of 100 mg or 300 mg administered intravenously every 12 weeks. Defining the appropriate dosing of eptinezumab in children and adolescents is required to accurately examine the safety and efficacy of its use as a preventive migraine therapy. METHODS: In this open-label PK clinical trial conducted between August 2020 and October 2022, children and adolescents with migraine (aged 6-17 years) received weight-adjusted intravenous eptinezumab infusions. The doses were designed to match the exposure from a 300 mg dose in adults. The trial included a 28-day screening period, a 20-week main trial period, and an optional 44-week multiple-dose extension period. Participants were dosed on Day 1 and had follow-up visits at Weeks 4, 8, 12, and 20. The extension period included three additional eptinezumab infusions every 12 weeks. Primary PK endpoints included area under the curve (from zero to infinity; AUC(0-inf)) of eptinezumab and maximum concentration (C(max)). The effect of eptinezumab on migraine-related disability was explored using the Pediatric Migraine Disability Assessment. RESULTS: A total of 28 participants (12 children [aged 6-11 years] and 16 adolescents [aged 12-17 years]) were enrolled in the trial, with 23 continuing into the extension period. A single intravenous administration of eptinezumab at 150 mg or 300 mg resulted in similar mean plasma concentration-time curves (mean AUC(0-inf): 92,890 h·μg/mL [150 mg], 95,550 h·μg/mL [300 mg]; mean C(max): 131.8 μg/mL [150 mg], 141.2 μg/mL [300 mg]). The PK profile of eptinezumab after multiple intravenous administrations in the extension period was also similar. No serious adverse events (AEs) or severe treatment-emergent AEs (TEAEs) were observed. The most common TEAE was orthostatic hypotension, reported in three adolescents (11% of total population). Other TEAEs occurred as single incidences. Improvement in migraine-associated disability was seen in both children and adolescents after a single intravenous administration of eptinezumab (median [range] score changes from baseline to Week 12 were -22 [-70, -6] in children and -17.0 [-117, 42] in adolescents) and was maintained during the extension period. CONCLUSION: The PK profile in children and adolescents was consistent across different dose levels and weight groups. These results support the use of weight-based eptinezumab dosing in children and adolescents with migraine. Eptinezumab was generally well tolerated, with no new safety signals observed in this population relative to those observed in adults.