A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine

Abstract

Background: Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. This study evaluated the safety and tolerability, as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine.

Methods: Patients diagnosed with episodic or chronic migraine, 18 to 65 years old, that were not exposed previously to galcanezumab, were randomized to receive galcanezumab 120 mg or 240 mg, administered subcutaneously once monthly for a year. Safety and tolerability were evaluated by frequency of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to study discontinuation. Laboratory values, vital signs, electrocardiograms, and suicidality were also analyzed. Additionally, overall change from baseline in the number of monthly migraine headache days, functioning, and disability were assessed.

Results: One hundred thirty five patients were randomized to each galcanezumab dose group. The majority of patients were female (> 80%) and on average were 42 years old with 10.6 migraine headache days per month at baseline. 77.8% of the patients completed the open-label treatment phase, 3.7% of patients experienced an SAE, and 4.8% discontinued due to AEs. TEAEs with a frequency ≥ 10% of patients in either dose group were injection site pain, nasopharyngitis, upper respiratory tract infection, injection site reaction, back pain, and sinusitis. Laboratory values, vital signs, or electrocardiograms did not show anyclinically meaningful differences between galcanezumab dosesOverall mean reduction in monthly migraine headache days over 12 months for the galcanezumab dose groups were 5.6 (120 mg) and 6.5 (240 mg). Level of functioning was improved and headache-related disability was reduced in both dose groups.

Conclusion: Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days. Safety and tolerability of the 2 galcanezumab dosing regimens were comparable.

Trial registration: ClinicalTrials.gov as NCT02614287 , posted November 15, 2015. These data were previously presented as a poster at the International Headache Congress 2017: PO-01-184, Late-Breaking Abstracts of the 2017 International Headache Congress. (2017). Cephalalgia, 37(1_suppl), 319-374.

Keywords: CGRP; Galcanezumab; Headache; Migraine.

Conflict of interest statement

Ethics approval and consent to participate

This study was reviewed and approved by appropriate institutional review boards and was conducted according to Good Clinical Practice and the Declaration of Helsinki. The ethical review boards included: Commissie Medische Ethiek Universitair Ziekenhuis (Institutes: Clinique St. Joseph, Algemeen Ziekenhuis St Jan Brugge, Universitair Ziekenhuis Brussel; Belgium), IRB Services (Institutes: DIEX Recherche Sherbrooke, Inc., Stroyan Research; Canada), Conjoint Medical Ethics Committee (Institute: University of Calgary, Canada), CPP Sud Mediterannée V (Institutes: CHU St Etienne Hôpital Nord, Hôpital de la Timone, Hôpital de Cimiez, Hôpital Lariboisiere; France), Egeszsegugyi Tudomanyos Tanacs (Institutes: Orszagos Idegtudomanyi Intezet, Petz Aladar Megyei Oktato Korhaz, SE Neurologiai Klinika, Valeomed Kft.; Hungary), Quorum Review, Inc. (Institutes: Wilmington Health Associates, Mercy Health Research, Blue Ridge Research Center, Jacksonville Center for Clinical Research, Ericksen Research and Development, Suburban Research Associates, California Medical Clinic for Headache, Albuquerque Neuroscience, Inc., ClinPoint Trials, LLC, Encompass Clinical Research, New England Institute for Clinical Research, Infinity Clinical Research, LLC, PharmQuest, Ponce School of Medicine CAIMED Center; USA).Patients provided written informed consent before initiating study procedures. The ethics committee approval covers all the sites in each country at the national level.

Consent for publication

Not applicable.

Competing interests

AC, SW, KJS, and VLS are full-time employees and minor shareholders of Eli Lilly and Company or one of its affiliates. RS was a full-time employee of Eli Lilly and Company at the time the manuscript was submitted. DK has received consultant fees from Eli Lilly, Amgen, Novartis and Alder and has received research support from Eli Lilly, Amgen, Alder, Teva, Allergan, Biohaven, CoLucid, VM Biopharma, and Roche-Genentech. AVD has received speaker fees from UCB, GSK, and Pfizer.

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Figures

Fig. 1

Patient cohort diagram through the treatment phase of the study

Fig. 2

Overall mean change from baseline in the number of monthly migraine headache days. *P < .05; **P < .01. Overall least squares (LS) mean change from baseline in the number of migraine headache days for patients who were treated with monthly open-label injections of galcanezumab 120 mg or 240 mg

Fig. 3

Maintenance of response. Percentage of patients treated with monthly injections of galcanezumab 120 mg or 240 mg, who had at least 50% or greater reduction from baseline in migraine headache days and maintained at least 40% reduction over 3 to 12 consecutive months