A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention. (January 2021)

• Record Type: Journal Article
• Authors: Ashina, Messoud; Doležil, David; Bonner, Jo H; Zhou, Lifen; Klatt, Jan; Picard, Hernan; Mikol, Daniel D
• Is Part Of: Cephalalgia. Volume 41:Number 1(2021)
• Page Start: 33
• Page End: 44
• Publication Date: 2021-01
• Subjects: AMG 301 -- chronic migraine -- episodic migraine -- pituitary adenylate cyclase-activating polypeptide -- preventive treatment; Headache -- Periodicals; 616.8491
• DOI: 10.1177/0333102420970889
• Languages: English
• ISSNs: 0333-1024

Abstract

Objective: To assess the safety and efficacy of AMG 301, an inhibitor of the pituitary adenylate cyclase-activating polypeptide (PACAP)-1 (PAC1) receptor, for prevention of migraine. Methods: In a double-blind trial, patients were randomized 4:3:3 to placebo, AMG 301 210 mg every 4 weeks, or AMG 301 420 mg every 2 weeks for 12 weeks. Effect on monthly migraine days and other secondary measures were assessed over weeks 9–12. Safety and tolerability were assessed. Results: Of 343 randomized patients (mean age, 41.8–42.5 years), the majority were women (85.4–90.4%), white (94.1–96.2%), and had episodic migraine (62.5–67.9%). A total of 305 patients completed treatment (placebo, n = 124; AMG 301 210 mg, n = 94; AMG 301 420 mg, n = 87). Least squares mean reduction at week 12 in monthly migraine days from baseline was −2.5 (0.4) days for placebo and −2.2 (0.5) days for both AMG 301 treatment groups. No difference between AMG 301 and placebo on any measure of efficacy was observed; mean (95% confidence interval) treatment difference versus placebo for monthly migraine days for AMG 301 210 mg, 0.3 (−0.9 to 1.4); AMG 301 420 mg, 0.3 (−0.9 to 1.4). The incidence of adverse events was similar across groups. Conclusion: AMG 301 offered no benefit over placebo for migraine prevention; further studies may be necessary to fully understand the role of PACAP isoforms and its receptors in migraine pathophysiology. Study Registration: ClinicalTrials.gov: NCT03238781