David W Dodick1, Richard B Lipton2, Stephen Silberstein3, Peter J Goadsby4,5, David Biondi6, Joe Hirman7, Roger Cady6, Jeff Smith8. 1. 1 Mayo Clinic, Phoenix, AZ, USA. 2. 2 Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, NY, USA. 3. 3 Jefferson Headache Center, Philadelphia, PA, USA. 4. 4 NIHR-Wellcome Trust King's Clinical Research Facility, SLaM Biomedical Research Centre, King's College London, UK. 5. 5 University of California San Francisco, San Francisco, CA, USA. 6. 6 Alder BioPharmaceuticals, Inc., Bothell, WA, USA. 7. 7 Pacific Northwest Statistical Consulting, Woodinville, WA, USA. 8. 8 Alder BioPharmaceuticals Ltd, Dublin, Ireland.
Abstract
BACKGROUND:Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. OBJECTIVE: To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. METHODS: This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial. Men and women (N = 616) aged 18-55 years were included if they had a diagnosis of chronic migraine, with onset at age ≤35 years and history of chronic migraine ≥1 year. During the 28-day screening period, patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks as recorded in the electronic diary. Patients were assigned in a 1:1:1:1:1 ratio to eptinezumab 300, 100, 30, 10 mg or placebo, administered as a single IV infusion. The primary endpoint was the percentage of patients with a ≥75% decrease in monthly migraine days over weeks 1-12 compared with the 28-day screening period. RESULTS: The ≥75% migraine responder rates over weeks 1-12 for eptinezumab 300, 100, 30, and 10 mg were 33.3%, 31.4%, 28.2%, and 26.8%, respectively, versus 20.7% for placebo (p = 0.033, 0.072, 0.201, 0.294 vs. placebo). Secondary efficacy endpoints (e.g. ≥50% responder rate, change from baseline in frequency of migraine/headache days, and percentage of severe migraines) had results favoring the three higher eptinezumab doses versus placebo. Eptinezumab was well tolerated and adverse event rates were similar to placebo. CONCLUSIONS: The results of this trial demonstrate that eptinezumab appears effective and well-tolerated for the preventive treatment of chronic migraine and justifies the conduct of pivotal phase 3 trials for migraine prevention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02275117.
RCT Entities:
BACKGROUND: Calcitonin gene-related peptide plays an important role in migraine pathophysiology. We evaluated eptinezumab, an intravenous (IV) anti-calcitonin gene-related peptide monoclonal antibody, for the prevention of chronic migraine. OBJECTIVE: To determine the safety, tolerability, and effectiveness of four dose levels of eptinezumab and to inform the phase 3 development program. METHODS: This was a phase 2b, parallel-group, double-blind, randomized, placebo-controlled, dose-ranging clinical trial. Men and women (N = 616) aged 18-55 years were included if they had a diagnosis of chronic migraine, with onset at age ≤35 years and history of chronic migraine ≥1 year. During the 28-day screening period, patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks as recorded in the electronic diary. Patients were assigned in a 1:1:1:1:1 ratio to eptinezumab 300, 100, 30, 10 mg or placebo, administered as a single IV infusion. The primary endpoint was the percentage of patients with a ≥75% decrease in monthly migraine days over weeks 1-12 compared with the 28-day screening period. RESULTS: The ≥75% migraine responder rates over weeks 1-12 for eptinezumab 300, 100, 30, and 10 mg were 33.3%, 31.4%, 28.2%, and 26.8%, respectively, versus 20.7% for placebo (p = 0.033, 0.072, 0.201, 0.294 vs. placebo). Secondary efficacy endpoints (e.g. ≥50% responder rate, change from baseline in frequency of migraine/headache days, and percentage of severe migraines) had results favoring the three higher eptinezumab doses versus placebo. Eptinezumab was well tolerated and adverse event rates were similar to placebo. CONCLUSIONS: The results of this trial demonstrate that eptinezumab appears effective and well-tolerated for the preventive treatment of chronic migraine and justifies the conduct of pivotal phase 3 trials for migraine prevention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02275117.
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