Monoclonal antibody against CGRP (TEV-48125) for preventive treatment of episodic cluster headache: a phase II randomized clinical trial protocol

Abstract

Background: Episodic Cluster Headache (CH) is the most prevalent and peculiar form of trigeminal autonomic cephalalgias. It is also considered the most severe among primary headache syndromes with a relevant destructive impact on quality of life, which makes it a highly disabling disorder. Despite availability of adequate options for acute attacks, at the present time there is no ideal effective preventive treatment for this condition. Preliminary evidence on treatment efficacy and safety of monoclonal antibodies against Calcitonin Gene-Related Peptide or its receptor has shown promising results as novel therapies for this type of disorder. The aim of this study is to analyze the effectiveness of the anti-CGRP antibody TEV-48125 against placebo, as a preventive strategy for episodic cluster headache on reducing the frequency of headache attacks during a headache episode. Methods: This study is a randomized, single-center, placebo controlled, triple-blind, parallel group trial with 1:1 allocation of 60 patients newly diagnosed with episodic CH to receive after an 8-week baseline observation phase either monoclonal anti-CGRP antibody TEV-48125 or placebo at weeks 1 and 5 over the course of 8 weeks during the experimental phase. Frequency of attacks will be assessed per week for 8 weeks during the baseline observation phase and the experimental phase. Primary endpoint is the reduction in frequency of headache attacks from baseline during a cluster headache episode compared to placebo. Discussion: This trial is a triple-blinded randomized placebo-controlled trial for a rare disease where preventive treatment is urgently needed. Potential limitations and challenges are the triple-blind approach and patient adherence, but will be handled to keep the impact at minimum.