TY - JOUR

T1 - 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

AU - Ashina, Messoud

AU - Doležil, David

AU - Bonner, Jo H.

AU - Zhou, Lifen

AU - Klatt, Jan

AU - Picard, Hernan

AU - Mikol, Daniel D.

N1 - Publisher Copyright: © International Headache Society 2020.

PY - 2021

Y1 - 2021

N2 - 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

AB - 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

KW - AMG 301

KW - chronic migraine

KW - episodic migraine

KW - pituitary adenylate cyclase-activating polypeptide

KW - preventive treatment

U2 - 10.1177/0333102420970889

DO - 10.1177/0333102420970889

M3 - Journal article

C2 - 33231489

AN - SCOPUS:85096616539

VL - 41

SP - 33

EP - 44

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 1

ER -