RimegepAnt effectIvenesS and tolErability as Migraine Preventive Treatment

Migraine Clinical Trial

— RAISE  

Official title:

RimegepAnt effectIvenesS and tolErability as Migraine Preventive Treatment: a Prospective, Multicentric, Cohort Study (RAISE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06409832
• Other study ID #: RICe_3
• Status: Recruiting
• Start date: March 26, 2024
• Est. completion date: January 2026

Study information

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

Clinical Trial Summary

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

Description:

Rimegepant belongs to the gepants family, small molecules calcitonin gene- related peptide (CGRP) receptor antagonists. It is a new generation gepant, currently available as an orally disintegrating tablet at a single dose of 75 mg.

It has a double indication both for acute treatment for migraine with and without aura and preventive treatment of migraine. A previous randomized, placebo-controlled phase 2/3 trial demonstrated its effectiveness and tolerability in the preventive setting for patients with episodic and chronic migraine. Previous studies also demonstrated a good tolerability profile. The most commonly reported adverse events were nausea, nasopharyngitis, upper respiratory tract infections and urinary tract infections.

In this prospective multicentric study the investigators aim to evaluate rimegepant 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 take rimegepant 75 mg orally disintegrating tablet every other day for a time period related to 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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2026
• Est. primary completion date: January 1, 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 4 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.

• Changes in preventive treatments in the month before the first administration of rimegepant

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rimegepant 75 mg
Patients using Rimegepant 75 mg orally disintegrating tablet every other day as migraine prevention

Locations

Country	Name	City	State
Italy	SOD Centro Cefalee e Farmacologia Clinica, AOU Careggi	Florence
Italy	IRCCS National Neurological Institute "C. Mondino" Foundation	Pavia

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, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, IRCCS National Neurological Institute "C. Mondino" Foundation, Ospedale di Piove di Sacco, 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 (2)

Croop R, Lipton RB, Kudrow D, Stock DA, Kamen L, Conway CM, Stock EG, Coric V, Goadsby PJ. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2021 Jan 2;397(10268):51-60. doi: 10.1016/S0140-6736(20)32544-7. Epub 2020 Dec 15. — View Citation

Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, Dubowchik GM, Conway CM, Coric V, Goadsby PJ. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019 Jul 11;381(2):142-149. doi: 10.1056/NEJMoa1811090. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the number of monthly migraine days with aura (quantitative)	Changes in the number of monthly migraine days with aura across rimegepant treatment (continuous variable, through headache diary assessment)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	Variation of duration of aura (qualitative)	Changes in duration of aura across rimegepant treatment (categorical variable - minutes, assessed through headache diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	Variation of type of aura (qualitative)	Changes in type of aura across rimegepant treatment (assessed through headache diary and anamnestic data collection)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	MMDs reduction in patients Non-responders to mAbs	Change of monthly migraine days across rimegepant 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 rimegepant
Other	Percentage of 50% Responders in patients Non-responders to anti CGRP mAbs	Percentage of 50% Responders across rimegepant 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 rimegepant
Other	Menstrually-related migraine	Change in the number of menstrually-related attacks (according to ICHD-3) across rimegepant treatment compared to baseline (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	Change in self-reported effectiveness of rimegepant 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)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
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 rimegepant
Other	Changes in migraine duration across treatment	Changes in migraine duration across treatment (continuous variable, hours, assessed through a paper diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	Changes in duration of the most bothersome symptom(s)	Changes in duration of the most bothersome symptom(s) (continuous variable, minutes, assessed through a paper diary)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Other	Changes in severity of the most bothersome symptom(s)	Changes in severity of the most bothersome symptom(s) (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 rimegepant
Other	Changes in self-reported effectiveness of acute treatment	Changes in self-reported effectiveness of usual acute treatment (Patients Global Impression of Change 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 rimegepant
Primary	Changes in migraine frequency after three months of treatment	Changes in monthly migraine days after three months of treatment with rimegepant compared to baseline (continuous variable)	Baseline (T0) - 3 months of treatment with rimegepant (T3)
Primary	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment with rimegepant	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after three months of treatment with rimegepant	Baseline (T0) - 3 months of treatment with rimegepant (T3)
Secondary	Changes in migraine frequency across twelve months of rimegepant treatment	Change of monthly migraine days after six and twelve months of treatment with rimegepant compared to baseline (continuous variable)	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) across twelve months of treatment with rimegepant	Percentage of 50% Responders (namely patients who presented a reduction of MMDs >/ = 50% compared to baseline) after six and twelve months of treatment with rimegepant	Baseline (T0) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Evaluation of any adverse event (qualitative)	Type of any adverse events in patients receiving rimegepant during the observation period (categorical variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Evaluation of any adverse event (quantitative)	Percentage of reported adverse events in patients receiving rimegepant during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
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 rimegepant during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Evaluation of adverse event leading to treatment discontinuation	Percentage of adverse events leading to treatment discontinuation in patients receiving rimegepant during the observation period (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Consistency of treatment response	Percentage of patients with a stable 50% response during rimegepant treatment ( from 3 to 12 months of treatment) (continuous variable)	3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Changes in migraine disability (MIDAS)	Changes in MIgraine Disability ASsement questionnaire across rimegepant 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 rimegepant
Secondary	Changes in migraine disability (HIT-6)	Changes in Headache Impact Test-6 questionnaire across rimegepant 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 rimegepant
Secondary	Changes in response to acute migraine treatment (m-TOQ)	Changes in migraine Treatment Optimization Questionnaire across rimegepant 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 rimegepant
Secondary	Changes in allodynia across rimegepant treatment (ASC-12)	Changes in Allodynia Symptoms Checklist-12 questionnaire across rimegepant 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 rimegepant
Secondary	Changes in quality of life across rimegepant treatment (MSQ)	Changes in Migraine Specific Quality of life questionnaire across rimegepant treatment (continuous variable, 0-100 scale, 100 indicates full functionality)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant
Secondary	Changes in interictal burden across rimegepant treatment (MIBS-4)	Changes in Migraine Interictal Burden Scale-4 questionnaire across rimegepant 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 rimegepant
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 rimegepant treatment (continuous variable)	Baseline (T0) - 3 months (T3) - 6 months (T6) - 12 months (T12) of treatment with rimegepant