## Protocol Section
### Identification Module
**NCT ID:** NCT06414044

**Acronym:** STAR

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

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

#### Organization Study ID Info
**ID:** RICe_4
#### Organization
**Class:** OTHER
**Full Name:** University of Florence
### Status Module
#### Completion Date
**Date:** 2026-04

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-10

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-09

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-10
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Fondazione Policlinico Universitario Campus Bio-Medico

**Class:** OTHER

**Name:** IRCCS National Neurological Institute "C. Mondino" Foundation

**Class:** UNKNOWN

**Name:** Società italiana per lo studio delle Cefalee (SISC)

**Class:** OTHER

**Name:** Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

**Class:** OTHER

**Name:** Università degli Studi dell'Aquila

**Class:** OTHER

**Name:** University of Roma La Sapienza

**Class:** OTHER

**Name:** Azienda Ospedaliero Universitaria Policlinico Modena

**Class:** UNKNOWN

**Name:** Euganea Health Unit, Padua, Italy

**Class:** OTHER

**Name:** Azienda Ospedaliero-Universitaria di Parma

**Class:** OTHER

**Name:** Azienda Ospedaliera S. Maria della Misericordia

**Class:** OTHER

**Name:** Azienda Ospedaliera Città della Salute e della Scienza di Torino

**Class:** OTHER

**Name:** Cliniche Humanitas Gavazzeni

**Class:** OTHER

**Name:** University of Campania "Luigi Vanvitelli"

**Class:** UNKNOWN

**Name:** Ospedale di Prato

**Class:** OTHER

**Name:** Azienda Policlinico Umberto I

**Class:** UNKNOWN

**Name:** Auxologico San Luca, Milano

**Class:** UNKNOWN

**Name:** ASST Spedali Civili, Brescia

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Florence

#### Responsible Party

**Investigator Affiliation:** University of Florence

**Investigator Full Name:** Luigi Francesco Iannone

**Investigator Title:** Researcher at the Headache Center and Clinical Pharmacology Unit and at the Department of Health Sciences, University of Florence, Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Migraine

- Migraine With Aura

- Migraine Without Aura

- Chronic Migraine

**Keywords:**

- Headache

- Medication overuse headache

- Pain

- Migraine prevention

- Gepant

### Design Module

#### Design Info

**Observational Model:** CASE_ONLY

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients affected by migraine with an episodic pattern (\< 15 monthly migraine days) with or without aura according to ICHD-III criteria.

**Intervention Names:**

- Drug: Atogepant 60 mg

**Label:** Episodic migraine

#### Arm Group 2

**Description:** Patients affected by chronic migraine (\> 15 monthly headache days with at least 8 days with migraine features) according to ICHD-III criteria.

**Intervention Names:**

- Drug: Atogepant 60 mg

**Label:** Chronic migraine

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Chronic migraine

- Episodic migraine

**Description:** Patients using atogepant 60 mg tablet daily as migraine prevention

**Name:** Atogepant 60 mg

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Changes in monthly migraine days with aura across treatment (continuous variable, through headache diary assessment)

**Measure:** Changes in the number of monthly migraine days with aura (quantitative)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in duration of aura across atogepant treatment (continuous variable - minutes, assessed through headache diary)

**Measure:** Variation of duration of aura (qualitative)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in type of aura across atogepant treatment (qualitative variable - assessed through headache diary and anamnestic data collection)

**Measure:** Variation of type of aura (qualitative)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Change of monthly migraine days across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)

**Measure:** MMDs reduction in patients Non-responders to mAbs

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Percentage of 50% Responders across treatment in those patients who did not respond to anti-CGRP mAbs (continuous variable)

**Measure:** Percentage of 50% Responders across treatment in patients Non-responders to mAbs

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Change in the number of menstrually-related attacks (according to ICHD-3) across treatment compared to baseline (continuous variable)

**Measure:** Menstrually-related migraine

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Change in self-reported effectiveness of treatment

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in migraine severity (continuous variable, 0-10 numerical rating scale, higher scores indicate higher severity)

**Measure:** Changes in migraine severity

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in migraine duration (continuous variable- hours- assessed through a paper diary)

**Measure:** Changes in migraine duration

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in duration of the most bothersome symptom(s) across treatment (continuous variable, minutes, assessed through a paper diary)

**Measure:** Changes in duration of the most bothersome symptom(s)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in severity of the most bothersome symptom(s) across treatment (continuous variable: 0-10 scale, higher scores indicate higher severity )

**Measure:** Changes in severity of the most bothersome symptom(s)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

#### Primary Outcomes

**Description:** Changes in monthly migraine days after three months of treatment with atogepant compared to baseline (continuous variable)

**Measure:** Changes in migraine frequency after three months of treatment

**Time Frame:** Baseline (T0) - 3 months of treatment with atogepant (T3)

**Description:** 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)

**Measure:** 50% Response after three months of treatment

**Time Frame:** Baseline (T0) - 3 months of treatment with atogepant (T3)

#### Secondary Outcomes

**Description:** Changes in monthly migraine days after six and twelve months of treatment with atogepant compared to baseline (continuous variable)

**Measure:** Changes in migraine frequency across twelve months of atogepant treatment

**Time Frame:** Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with atogepant

**Time Frame:** Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Type of any adverse events in patients receiving atogepant during the observation period (categorical variable)

**Measure:** Evaluation of any adverse event (qualitative)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Percentage of reported adverse events in patients receiving atogepant assessed quarterly during the observation period (continuous variable)

**Measure:** Evaluation of any adverse event (quantitative)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Evaluation of serious adverse event

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Percentage of adverse events leading to treatment discontinuation in patients receiving atogepant during the observation period (continuous variable)

**Measure:** Evaluation of adverse event leading to treatment discontinuation

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Percentage of patients with a stable 50% response across twelve months of atogepant treatment (continuous variable)

**Measure:** Consistency of treatment response

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Changes in migraine disability (MIDAS)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in Headache Impact Test-6 questionnaire across treatment (continuous variable, 36-78 scale, higher scores indicates greater disability)

**Measure:** Changes in migraine disability (HIT-6)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in migraine Treatment Optimization Questionnaire across treatment (continuous variable, 0-8 scale, higher score indicates higher acute therapy effectiveness)

**Measure:** Changes in response to acute migraine treatment (m-TOQ)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in Allodynia Symptoms Checklist-12 questionnaire across treatment (continuous variable, 0-24 scale, higher score indicates more severe allodynia)

**Measure:** Changes in allodynia (ASC-12)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Changes in Migraine Specific Quality of life questionnaire across treatment (continuous variable, 0-100 scale, 100 indicates full functionality)

**Measure:** Changes in quality of life across atogepant treatment (MSQ)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Changes in interictal burden across atogepant treatment (MIBS-4)

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** 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)

**Measure:** Self-reported treatment effectiveness

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

**Description:** Percentage of patients with a baseline diagnosis of MOH reverted after 3 - 6 and 12 months of treatment (continuous variable)

**Measure:** Percentage of patients with Medication overuse headache reverted during treatment

**Time Frame:** Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with atogepant

### Eligibility Module

**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);
* 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.

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Multicentric study on patients attending the outpatient clinic of Italian Headache centres who meet criteria for atogepant use for migraine preventive treatment.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** luigifrancesco.iannone@unifi.it

**Name:** Luigi F Iannone, MD

**Phone:** +393896969606

**Role:** CONTACT

**Contact 2:**

**Email:** f.vernieri@policlinicocampus.it

**Name:** Fabrizio Vernieri, MD

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Florence

**Contacts:**

***Contact 1:***

- **Email:** luigifrancesco.iannone@unifi.it

- **Name:** Luigi F Iannone, MD

- **Role:** CONTACT

**Country:** Italy

**Facility:** SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi

**Status:** RECRUITING

**Zip:** 50134

**Location 2:**

**City:** Roma

**Contacts:**

***Contact 1:***

- **Name:** Fabrizio Vernieri

- **Role:** CONTACT

**Country:** Italy

**Facility:** Fondazione Policlinico Campus Bio-Medico

**Status:** RECRUITING

**Zip:** 00128

### References Module

#### References

**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.

**PMID:** 37516125

**Citation:** 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.

**PMID:** 32822633

**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.

**PMID:** 34521260

**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.

**PMID:** 38364831

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000051270

- Term: Headache Disorders, Primary

- ID: D000020773

- Term: Headache Disorders

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9351

- Name: Headache

- Relevance: LOW

- As Found: Unknown

- ID: M11852

- Name: Migraine Disorders

- Relevance: HIGH

- As Found: Migraine

- ID: M13066

- Name: Pain

- Relevance: LOW

- As Found: Unknown

- ID: M22135

- Name: Migraine without Aura

- Relevance: HIGH

- As Found: Migraine Without Aura

- ID: M22134

- Name: Migraine with Aura

- Relevance: HIGH

- As Found: Migraine With Aura

- ID: M151

- Name: Prescription Drug Overuse

- Relevance: LOW

- As Found: Unknown

- ID: M22529

- Name: Headache Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M26657

- Name: Headache Disorders, Primary

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008881

- Term: Migraine Disorders

- ID: D000020326

- Term: Migraine without Aura

- ID: D000020325

- Term: Migraine with Aura

### Misc Info Module

- Version Holder: 2024-05-31
