Effectiveness and Tolerability of Eptinezumab (TACHIS)

Effectiveness and Tolerability of Eptinezumab: a Prospective, Multicentric, Cohort Study

The purpose of this prospective and multicentric study is to evaluate the effectiveness and tolerability of eptinezumab as preventive migraine treatment in a cohort of episodic or chronic migraine patients.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Chronic Migraine; Migraine Without Aura; Migraine With Aura
• Intervention / Treatment: Drug: Eptinezumab 100 or 300 mg ev

Detailed Description

Eptinezumab belongs to the monoclonal antibodies directed against the calcitoning gene related peptide - CGRP (mAbs). It is actually the only mAb administered intravenously, currently available at the dose of 100 or 300mg with a quarterly iv infusion.

It has an indication for migraine prevention for episodic and chronic migraine. Previous randomized, placebo-controlled clinical trials proved its effectiveness in the preventive setting for patients with episodic and chronic migraine.

Moreover, a previous study also supported evidence of faster headache pain freedom and most bothersome symptom resolution after eptinezumab 100mg infusion during migraine acute attack compared to placebo.

RCTs also demonstrated a good tolerability profile. The most commonly reported adverse events were mainly upper respiratory tract infections, fatigue and hypersensitivity reactions.

In this prospective multicentric study the investigators aim to evaluate eptinezumab effectiveness and tolerability as preventive migraine treatment in a real-world setting.

Subjects who meet the inclusion criteria will be enrolled and will participate in the study. Baseline demographic and clinical data will be collected at the baseline visit. The observation period will last for two years during which patients will be administered eptinezumab 100 or 300 mg according to clinicians' judgment, for a time period related to Italian Medicines Agency reimbursability criteria.

Data will be collected at baseline and every three months, up to two years. Subjects will be asked to keep a headache diary to collect monthly headache and migraine days, migraine severity, associated symptoms and drug consumption. Questionnaires will be collected every three months.

Data collection will focus on: i) demographic data, ii) migraine history, iii) pain intensity, iv) presence and evolution of migraine associated symptoms and aura, v) migraine associated disability, vi) tolerability and eventual treatment- emergent adverse events, vii) treatment persistence, viii) questionnaires related to disability, allodynia, quality of life, interictal burden and effectiveness of the ongoing acute and preventive treatments. The online database REDCap will be used for data collection.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Luigi F Iannone, mD; Phone Number: +39 3896969606; Email: luigifrancesco.iannone@unifi.it
• Study Contact Backup: Name: Simona Guerzoni, MD

Study Locations

• Italy
  • Florence, Italy, 50134
    • Recruiting
    • SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi
    • Contact: Luigi F Iannone, MD; Email: luigifrancesco.iannone@unifi.it
  • Modena, Italy, 41124
    • Not yet recruiting
    • AOU Policlinico Di Modena
    • Contact: Simona Guerzoni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Multicentric study on patients attending the outpatient clinic of Italian Headache centres who meet criteria for eptinezumab use as migraine preventive treatment

Description

Inclusion Criteria:

• Diagnosis of migraine without aura, migraine with aura, or chronic migraine according to the 3rd edition of the International Classification of Headache Disorder (ICHD-III);
• Good compliance to study procedures;
• Availability of headache diary at least of the preceding months before enrolment;
• At least 8 monthly migraine days.

Exclusion Criteria:

• Subjects with contraindications for use of eptinezumab;
• Concomitant diagnosis of medical diseases and/or comorbidities that, in the Investigator's opinion might interfere with study assessments;
• medical comorbidities that could interfere with study results;
• Pregnancy and breastfeeding
• Changes in preventive treatments in the month before the first administration of eptinezumab

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Episodic migraine; Patients affected by migraine with an episodic pattern (< 15 monthly migraine days) with or without aura according to ICHD-III criteria.	Drug: Eptinezumab 100 or 300 mg ev; Patients administered eptinezumab 100 or 300 mg ev quarterly for migraine prevention; Other Names: Eptinezumab
Chronic migraine; atients affected by chronic migraine (> 15 monthly headache days with at least 8 days with migraine features) according to ICHD-III criteria.	Drug: Eptinezumab 100 or 300 mg ev; Patients administered eptinezumab 100 or 300 mg ev quarterly for migraine prevention; Other Names: Eptinezumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in migraine frequency after three months of treatment	Changes in monthly migraine days after three months of treatment with eptinezumab compared to baseline (continuous variable)	Baseline (T0) - 3 months of treatment with eptinezumab (T3)
Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment with eptinezumab (continuous variable)	Baseline (T0) - 3 months of treatment with eptinezumab (T3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in migraine frequency across twelve months of eptinezumab treatment	Changes in monthly migraine days after six and twelve months of treatment with eptinezumab compared to baseline (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with eptinezumab	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after six and twelve months of treatment with eptinezumab (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Evaluation of any adverse event (qualitative)	Type of any adverse events in patients receiving eptinezumab during the observation period (categorical variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Evaluation of any adverse event (quantitative)	Percentage of reported adverse events in patients receiving eptinezumab assessed quarterly during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Evaluation of serious adverse events	Percentage of serious adverse events (namely those resulting in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect) in patients receiving eptinezumab during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Evaluation of adverse events leading to treatment discontinuation	Percentage of adverse events leading to treatment discontinuation in patients receiving eptinezumab during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Consistency of treatment response	Percentage of patients with a stable 50% response across twelve months of eptinezumab treatment (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in migraine disability (MIDAS)	Changes in MIgraine Disability ASsesment questionnaire across treatment (continuous variable, 0-270 scale, higher scores indicate higher disability: 0-5, little/no disability; 6-10, mild disability; 11-20, moderate disability; >20, severe disability)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in migraine disability (HIT-6)	Changes in Headache Impact Test-6 questionnaire across treatment (continuous variable, 36-78 scale, higher scores indicates greater disability)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in response to acute migraine treatment (m-TOQ)	Changes in migraine Treatment Optimization Questionnaire across eptinezumab treatment (continuous variable, 0-8 scale, higher score indicates higher acute therapy effectiveness)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in allodynia (ASC-12)	Changes in Allodynia Symptoms Checklist-12 questionnaire across treatment (continuous variable, 0-24 scale, higher score indicates more severe allodynia)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in interictal burden across eptinezumab treatment (MIBS-4)	Changes in Migraine Interictal Burden Scale-4 questionnaire across treatment (continuous variable, 0-4 scale, 0 indicates no interictal burden, 1-2 mild level of interictal burden, 3 moderate interictal burden, 4 severe interictal burden)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Percentage of patients with Medication overuse headache reverted during treatment	Percentage of patients with a baseline diagnosis of MOH reverted after 3 - 6 and 12 months of eptinezumab treatment (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the number of monthly migraine days with aura (quantitative)	Changes in monthly migraine days with aura across twelve months treatment (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Variation of duration of aura (qualitative)	Changes in duration of aura across eptinezumab treatment (categorical variable - minutes, assessed through headache diary)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Variation of type of aura (qualitative)	Changes in type of aura across eptinezumab treatment (assessed through headache diary and anamnestic data collection)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
MMDs reduction in patients Non-responders to other anti-CGRP mAbs	Change of monthly migraine days across eptinezumab twelve-months treatment in those patients who did not respond to other anti-CGRP mAbs (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Percentage of 50% Responders in patients Non-responders to other anti-CGRP mAbs	Percentage of 50% Responders across eptinezumab treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in migraine duration across treatment	Changes in migraine duration (continuous variable, hours, assessed through a paper diary)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in migraine severity across treatment	Changes in migraine severity across treatment (continuous variable, 0-10 numerical rating scale, higher scores indicate higher severity)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in duration of the most bothersome symptom(s)	Changes in duration of the most bothersome symptom(s) across treatment (continuous variable: minutes, assessed through a paper diary)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in severity of the most bothersome symptom(s)	Changes in durantion and severity of the most bothersome symptom(s) (continuous variable: 0-10 numerical rating scale, higher scores indicate higher severity)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in self-reported effectiveness of eptinezumab treatment	Changes in Patients Global Impression of Change (PGIC) questionnaire across treatment (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in self-reported effectiveness of acute treatment	Changes in self-reported effectiveness of usual acute treatment (qualitative variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Changes in perimenstrual attacks	Changes in duration, intensity and associated symptoms of perimenstrual attacks	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Azienda Ospedaliera Città della Salute e della Scienza di Torino; University of Roma La Sapienza; University of Campania "Luigi Vanvitelli"; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Azienda Ospedaliero-Universitaria di Parma; Azienda Ospedaliera S. Maria della Misericordia; IRCCS National Neurological Institute "C. Mondino" Foundation; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari; Università degli Studi dell'Aquila; Azienda Policlinico Umberto I; Cliniche Humanitas Gavazzeni; ASST Spedali Civili, Brescia; Azienda Ospedaliero Universitaria Policlinico Modena; Società italiana per lo studio delle Cefalee (SISC); Ospedale di Prato; Auxologico San Luca, Milano; Euganea Health Unit, Padua, Italy

Publications and helpful links

General Publications

• Ashina M, Lanteri-Minet M, Pozo-Rosich P, Ettrup A, Christoffersen CL, Josiassen MK, Phul R, Sperling B. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2022 Jul;21(7):597-607. doi: 10.1016/S1474-4422(22)00185-5.
• Dodick DW, Lipton RB, Silberstein S, Goadsby PJ, Biondi D, Hirman J, Cady R, Smith J. Eptinezumab for prevention of chronic migraine: A randomized phase 2b clinical trial. Cephalalgia. 2019 Aug;39(9):1075-1085. doi: 10.1177/0333102419858355. Epub 2019 Jun 24.
• Winner PK, McAllister P, Chakhava G, Ailani J, Ettrup A, Krog Josiassen M, Lindsten A, Mehta L, Cady R. Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial. JAMA. 2021 Jun 15;325(23):2348-2356. doi: 10.1001/jama.2021.7665.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 5, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Pain; Headache; Medication overuse headache; Migraine prevention; Anti-CGRP monoclonal antibodies; eptinezumab
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine without Aura; Migraine with Aura
• Other Study ID Numbers: RICe_5

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No