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

Migraine Clinical Trial

— STAR  

Official title:

STudio Osservazionale Sull'Efficacia, Sicurezza e tollerabilità di Atogepant in Pazienti Real Life Affetti da Emicrania in Italia (Studio STAR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06414044
• Other study ID #: RICe_4
• Status: Recruiting
• Start date: May 9, 2024
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: University of Florence
• Contact: Luigi F Iannone, MD
• Phone: +393896969606
• Email: luigifrancesco.iannone[@]unifi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Migraine
• Migraine
• Migraine Disorders
• Migraine with Aura
• Migraine Without Aura

Intervention

Drug:
• Atogepant 60 mg
Patients using atogepant 60 mg tablet daily as migraine prevention

Locations

Country	Name	City	State
Italy	SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi	Florence
Italy	Fondazione Policlinico Campus Bio-Medico	Roma

Sponsors (18)

Lead Sponsor

Collaborator

University of Florence

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

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, Szegedi A. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020 Sep;19(9):727-737. doi: 10.1016/S1474-4422(20)30234-9. Erratum In: Lancet Neurol. 2020 Nov;19(11):e10. — View Citation

Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, Guo H, Schwefel B, Lu K, Boinpally R, Miceli R, De Abreu Ferreira R, McCusker E, Yu SY, Severt L, Finnegan M, Trugman JM. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Sep 2;402(10404):775-785. doi: 10.1016/S0140-6736(23)01049-8. Epub 2023 Jul 26. Erratum In: Lancet. 2023 Sep 2;402(10404):774. Lancet. 2023 Oct 14;402(10410):1328. — View Citation

Schwedt TJ, Lipton RB, Ailani J, Silberstein SD, Tassorelli C, Guo H, Lu K, Dabruzzo B, Miceli R, Severt L, Finnegan M, Trugman JM. Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial. Cephalalgia. 2022 Jan;42(1):3-11. doi: 10.1177/03331024211042385. Epub 2021 Sep 14. — View Citation

Tassorelli C, Nagy K, Pozo-Rosich P, Lanteri-Minet M, Sacco S, Nezadal T, Guo H, De Abreu Ferreira R, Forero G, Trugman JM. Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. Lancet Neurol. 2024 Apr;23(4):382-392. doi: 10.1016/S1474-4422(24)00025-5. Epub 2024 Feb 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the number of monthly migraine days with aura (quantitative)	Changes in monthly migraine days with aura across treatment (continuous variable, through headache diary assessment)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Variation of duration of aura (qualitative)	Changes in duration of aura across atogepant treatment (continuous variable - minutes, assessed through headache diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Variation of type of aura (qualitative)	Changes in type of aura across atogepant treatment (qualitative variable - assessed through headache diary and anamnestic data collection)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	MMDs reduction in patients Non-responders to mAbs	Change of monthly migraine days across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Percentage of 50% Responders across treatment in patients Non-responders to mAbs	Percentage of 50% Responders across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Menstrually-related migraine	Change in the number of menstrually-related attacks (according to ICHD-3) across treatment compared to baseline (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Change in self-reported effectiveness of treatment	Change in Patients Global Impression of Change (PGIC) questionnaire across treatment (continuous variable, scale 0-7, 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Changes in migraine severity	Changes in migraine severity (continuous variable, 0-10 numerical rating scale, higher scores indicate higher severity)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Changes in migraine duration	Changes in migraine duration (continuous variable- hours- assessed through a paper diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Other	Changes in severity of the most bothersome symptom(s)	Changes in severity of the most bothersome symptom(s) across treatment (continuous variable: 0-10 scale, higher scores indicate higher severity )	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Primary	Changes in migraine frequency after three months of treatment	Changes in monthly migraine days after three months of treatment with atogepant compared to baseline (continuous variable)	Baseline (T0) - 3 months of treatment with atogepant (T3)
Primary	50% Response 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 atogepant (continuous variable)	Baseline (T0) - 3 months of treatment with atogepant (T3)
Secondary	Changes in migraine frequency across twelve months of atogepant treatment	Changes in monthly migraine days after six and twelve months of treatment with atogepant compared to baseline (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months 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)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Evaluation of any adverse event (qualitative)	Type of any adverse events in patients receiving atogepant during the observation period (categorical variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Evaluation of any adverse event (quantitative)	Percentage of reported adverse events in patients receiving atogepant assessed quarterly during the observation period (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Evaluation of serious adverse event	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Evaluation of adverse event leading to treatment discontinuation	Percentage of adverse events leading to treatment discontinuation in patients receiving atogepant during the observation period (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Consistency of treatment response	Percentage of patients with a stable 50% response across twelve months of atogepant treatment (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Changes in migraine disability (MIDAS)	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Changes in response to acute migraine treatment (m-TOQ)	Changes in migraine Treatment Optimization Questionnaire across treatment (continuous variable, 0-8 scale, higher score indicates higher acute therapy effectiveness)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Changes in quality of life across atogepant treatment (MSQ)	Changes in Migraine Specific Quality of life questionnaire across treatment (continuous variable, 0-100 scale, 100 indicates full functionality)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Changes in interictal burden across atogepant 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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	Self-reported treatment effectiveness	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)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant
Secondary	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 treatment (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant