Italian Real-life obServational Study on the effecTiveness, sAfety and Tolerability of Atogepant in Migraine Patients

Recruiting

• Conditions: Migraine With Aura; Migraine Without Aura; Chronic Migraine; Migraine
• Interventions: Drug: Atogepant 60 mg

• Registration Number: NCT06414044
• Lead Sponsor: University of Florence

Brief Summary

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

Detailed Description

Atogepant is a small molecule calcitonin gene- related peptide (CGRP) receptor antagonist, part of the gepants family. It is a second generation gepant, currently approved for the preventive treatment of episodic and chronic migraine.

Previously randomized, placebo-controlled phase 2/3 trials demonstrated its effectiveness and tolerability in the preventive setting for patients with episodic and chronic migraine, associated with a good tolerability profile.

The most commonly reported adverse events were upper respiratory tract infections, urinary infections, nausea and constipation.

In this prospective multicentric study the investigators aim to evaluate atogepant 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.

patients will take atogepant 60 mg daily for at least 12 weeks up to two years, according to effectiveness, tolerability and eventual approval of reimbursability criteria.

Data will be collected at baseline and every three months for 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. The online database REDCap will be used for data collection.

Study Timeline

• Status Verified: 2024-05
• Study Start: 2024-05-09
• Study First Submitted: 2024-05-10
• Study First Submitted QC: 2024-05-10
• Last Update Submitted: 2024-05-10
• Study First Posted: 2024-05-14
• Last Update Posted: 2024-05-14
• Primary Completion: 2025-09
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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);
• At least 3 monthly migraine days;
• Good compliance to study procedures;
• Availability of headache diary at least of the preceding months before enrollment.

Exclusion Criteria

• Subjects with contraindications for use of gepants;
• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Episodic migraine	Atogepant 60 mg	Patients affected by migraine with an episodic pattern (\< 15 monthly migraine days) with or without aura according to ICHD-III criteria.
Chronic migraine	Atogepant 60 mg	Patients affected by chronic migraine (\> 15 monthly headache days with at least 8 days with migraine features) according to ICHD-III criteria.

Primary Outcome Measures

Name	Time	Method
Changes in migraine frequency after three months of treatment	Baseline (T0) - 3 months of treatment with atogepant (T3)	Changes in monthly migraine days after three months of treatment with atogepant compared to baseline (continuous variable)
50% Response after three months of treatment	Baseline (T0) - 3 months of treatment with atogepant (T3)	Percentage of 50% Responders (namely patients who presented a reduction of MMDs \>/ = 50% compared to baseline) after three months of treatment with atogepant (continuous variable)

Secondary Outcome Measures

Name	Time	Method
Consistency of treatment response	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Percentage of patients with a stable 50% response across twelve months of atogepant treatment (continuous variable)
Changes in allodynia (ASC-12)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in Allodynia Symptoms Checklist-12 questionnaire across treatment (continuous variable, 0-24 scale, higher score indicates more severe allodynia)
Changes in migraine disability (HIT-6)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in Headache Impact Test-6 questionnaire across treatment (continuous variable, 36-78 scale, higher scores indicates greater disability)
Changes in migraine frequency across twelve months of atogepant treatment	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in monthly migraine days after six and twelve months of treatment with atogepant compared to baseline (continuous variable)
Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with atogepant	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Percentage of 50% Responders (namely patients who presented a reduction of MMDs \>/ = 50% compared to baseline) after six and twelve months of treatment with atogepant (continuous variable)
Self-reported treatment effectiveness	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in Migraine Assessment of Current Therapy (Migraine-ACT) a 4-item questionnaire about treatment effectiveness and daily life repercussions, across treatment compared to baseline (continuous variable, 0-4 scale, higher scores indicates higher acute treatment effectiveness)
Evaluation of any adverse event (qualitative)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Type of any adverse events in patients receiving atogepant during the observation period (categorical variable)
Evaluation of any adverse event (quantitative)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Percentage of reported adverse events in patients receiving atogepant assessed quarterly during the observation period (continuous variable)
Evaluation of serious adverse event	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	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 atogepant during the observation period (continuous variable)
Changes in migraine disability (MIDAS)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in MIgraine Disability ASsement 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)
Evaluation of adverse event leading to treatment discontinuation	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Percentage of adverse events leading to treatment discontinuation in patients receiving atogepant during the observation period (continuous variable)
Changes in response to acute migraine treatment (m-TOQ)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in migraine Treatment Optimization Questionnaire across treatment (continuous variable, 0-8 scale, higher score indicates higher acute therapy effectiveness)
Changes in interictal burden across atogepant treatment (MIBS-4)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	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)
Percentage of patients with Medication overuse headache reverted during treatment	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Percentage of patients with a baseline diagnosis of MOH reverted after 3 - 6 and 12 months of treatment (continuous variable)
Changes in quality of life across atogepant treatment (MSQ)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant	Changes in Migraine Specific Quality of life questionnaire across treatment (continuous variable, 0-100 scale, 100 indicates full functionality)

Trial Locations

Locations (2)

SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi; 🇮🇹 Florence, Italy

Fondazione Policlinico Campus Bio-Medico; 🇮🇹 Roma, Italy