ALLEVIATE, a Clinical Trial-in-Progress of Eptinezumab in Patients With Episodic Cluster Headache
Stewart J. Tepper1, Neli Boneva2, Mette Krog Josiassen2, Elin Löf2, Rigmor Hoejland Jensen3
1Geisel School of Medicine at Dartmouth, 2H. Lundbeck A/S, 3Danish Headache Center, Rigshospitalet-Glostrup, University of Copenhagen
Objective:
To present the ALLEVIATE study design, a trial-in-progress evaluating the efficacy and safety of eptinezumab in patients with episodic cluster headache (eCH).
Background:
New, effective, fast-onset, and better-tolerated therapies are needed for eCH. Eptinezumab is a monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) and is indicated for migraine prevention in adults. Given the role of CGRP in cluster headache pathobiology and the demonstrated efficacy of one other anti-CGRP monoclonal antibody in eCH, eptinezumab may be effective in reducing cluster headache attack frequency.
Design/Methods:
ALLEVIATE (NCT04688775) is a phase 3, parallel-group, double-blind, placebo-controlled, delayed-start, randomized study. Eligible patients are adults (18‒75 years) with eCH and history of cluster headache bouts lasting ≥6 weeks. The first screening period lasts ≤52 weeks. Eligible patients, at the onset of a cluster headache bout, enter Screening Period 2, during which their weekly eCH attack frequency is determined. At baseline, patients will be randomized to, and treated with, intravenous eptinezumab 400mg or placebo, then receive the alternate study drug at Week 4. Due to a long half-life (27 days), eptinezumab will be bioavailable in patients for ≥12 weeks. The primary endpoint is change from baseline in number of weekly attacks over Weeks 1‒2. Key secondary endpoints include number of attacks starting within 24 hours of the first study drug administration, change from baseline in daily attacks over Days 1‒3, ≥50% reduction in weekly attacks over Weeks 1‒2, change from baseline in number of times an abortive therapy was used over Weeks 1‒2, and time to resolution of cluster headache bout within 4 weeks of the first study drug administration. Safety and tolerability will also be assessed. 
Results:
Currently recruiting; start date: 12/23/2020.
Conclusions:
This is the first study to evaluate the efficacy and safety of eptinezumab in patients with episodic cluster headache.