Clinical trial NCT06409845: Effectiveness and Tolerability of Eptinezumab
Official title: Effectiveness and Tolerability of Eptinezumab: a Prospective, Multicentric, Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Migraine
Migraine With Aura
Migraine Without Aura
Chronic Migraine
Keywords: Headache
Medication overuse headache
Pain
Migraine prevention
Anti-CGRP monoclonal antibodies
eptinezumab
Lead sponsor: University of Florence
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero Universitaria Policlinico Modena
name: Società Italiana per lo Studio delle Cefalee
name: IRCCS National Neurological Institute "C. Mondino" Foundation
name: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
name: Università degli Studi dell'Aquila
name: University of Roma La Sapienza
name: Euganea Health Unit, Padua, Italy
name: Azienda Ospedaliero-Universitaria di Parma
name: Azienda Ospedaliera S. Maria della Misericordia
name: A.O.U. Città della Salute e della Scienza
name: Cliniche Humanitas Gavazzeni
name: University of Campania Luigi Vanvitelli
name: Ospedale Santo Stefano
name: Azienda Policlinico Umberto I
name: Auxologico San Luca
name: Asst Degli Spedali Civili Di Brescia
name: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
First posted: 2024-05-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in migraine frequency after three months of treatment
timeFrame: Baseline (T0) - 3 months of treatment with eptinezumab (T3)
measure: Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment
timeFrame: Baseline (T0) - 3 months of treatment with eptinezumab (T3)
Secondary outcomes:
measure: Changes in migraine frequency across twelve months of eptinezumab treatment
timeFrame: Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with eptinezumab
timeFrame: Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Evaluation of any adverse event (qualitative)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Evaluation of any adverse event (quantitative)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Evaluation of serious adverse events
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Evaluation of adverse events leading to treatment discontinuation
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Consistency of treatment response
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in migraine disability (MIDAS)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in migraine disability (HIT-6)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in response to acute migraine treatment (m-TOQ)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in allodynia (ASC-12)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in interictal burden across eptinezumab treatment (MIBS-4)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Percentage of patients with Medication overuse headache reverted during treatment
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Other outcomes:
measure: Changes in the number of monthly migraine days with aura (quantitative)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Variation of duration of aura (qualitative)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Variation of type of aura (qualitative)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: MMDs reduction in patients Non-responders to other anti-CGRP mAbs
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Percentage of 50% Responders in patients Non-responders to other anti-CGRP mAbs
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in migraine duration across treatment
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in migraine severity across treatment
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in duration of the most bothersome symptom(s)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in severity of the most bothersome symptom(s)
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in self-reported effectiveness of eptinezumab treatment
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in self-reported effectiveness of acute treatment
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
measure: Changes in perimenstrual attacks
timeFrame: 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with eptinezumab
Locations:
city: Florence
country: Italy
facility: SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi
city: Modena
country: Italy
facility: AOU Policlinico Di Modena
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.