Clinical trial NCT06409832: RimegepAnt effectIvenesS and tolErability as Migraine Preventive Treatment
Official title: RimegepAnt effectIvenesS and tolErability as Migraine Preventive Treatment: a Prospective, Multicentric, Cohort Study (RAISE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Migraine
Migraine With Aura
Migraine Without Aura
Chronic Migraine
Keywords: Headache
Medication overuse headache
Pain
Migraine prevention
Gepant
Rimegepant
Lead sponsor: University of Florence
Sponsor class: OTHER
Collaborators: name: IRCCS National Neurological Institute "C. Mondino" Foundation
name: Società Italiana per lo Studio delle Cefalee
name: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
name: Università degli Studi dell'Aquila
name: University of Roma La Sapienza
name: Azienda Ospedaliero Universitaria Policlinico Modena
name: Ospedale di Piove di Sacco
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 rimegepant use for migraine preventive treatment.

Brief 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.

Detailed 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.

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 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

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