Clinical trial NCT05281770: Monoclonal CGRP Antibodies for Migraine Prevention - a Nationwide Real Life Study
Official title: Non-interventional Study of the Austrian Headache Society: Monoclonal CGRP Antibodies for Migraine Prevention a Nationwide Real Life Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Migraine
Migraine With Aura
Migraine Without Aura
Chronic Migraine
Episodic Migraine
Keywords: Erenumab
Galcanezumab
Fremanezumab
CGRP-antibodies
Lead sponsor: Austrian Migraine Registry Collaboration
Sponsor class: NETWORK
Collaborators: name: Medical University of Vienna
name: Medical University Innsbruck
name: Austrian Headache Society
First posted: 2022-03-16
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male or female adult patients of at least 18 years or older in whom CGRP mabs can be prescribed according to Austrian regulations. These include treatment failure or intolerability / contraindications of at least 3 prophylactic medications. Documentation of treatment in a headache diary on paper or in digital format.

Brief summary: The present non-interventional study on migraine prevention with monoclonal CGRP antibodies adresses questions concering safety, swichting from one CGRP mab to another, efficacy on auras in the real world setting.

Detailed description: Introduction:

Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) are an effective option for the preventative treatment in episodic and chronic migraine. All monoclonal antibodies against CGRP or CGRP-R have been proven efficacious in all various treatment endpoints (i.e. reduction of MMDs, improvement in Quality of Life etc.) in randomized phase 3 trials and were therefore approved by FDA and EMA. However, real world clinical experience/data in "non-study" patients is lacking as is data on long-term efficacy, elderly or data on switchers between antibodies that cannot be derived out of previous trials.

Phase 3 and 4 studies have addressed issues of efficacy and safety in highly selected clinical study populations and so far no safety concerns have emerged. However, long-term data are limited to a maximum period of 5 years and have been acquired in selected study cohorts probably not reflecting a "real world" patient population. It is a main goal of the study to acquire data on safety and efficacy in a real world setting where patients will be less selected than in clinical studies in terms of accompanying diseases or comorbidities. Another knowledge gap concerns the optimal procedure when switching the patient from one anti-CGRP therapy to another or being paused (and re-initiated) after a first successful treatment period. With specific evidence lacking, it is frequently recommended to wait several half-lives before initiating the next anti-CGRP therapy. Another unresolved question is whether non-responders to CGRP ligand blockers may respond to CGRP-receptor blockers and vice versa. While efficacy of anti-CGRP therapies has been demonstrated for migraine with and without aura, possible effects on the migraine auras per se have not been reported.

Phase 4 studies (non-interventional studies) on treatment with anti-CGRP therapies are being conducted in several countries in Europe. These are, however, limited to one specific substance. The proposed project will allow collecting data on the use of erenumab, fremanezumab, and galcanezumab on a nation- wide basis up to 36 months in a real-life setting.

The following knowledge should emerge from the registry:

Anti-CGRP therapies can be safely used in a wide spectrum of migraine patients with comorbidities and accompanying diseases over a long time period. There will be evidence how patients can be switched from one CGRP antibody to another. There will be an evidence base to switch anti-CGRP-therapies from ligand- to receptor- blockers or vice versa. Additionally the question whether a mAB even if effective should be paused or not after 1 year of treatment and what effect this pause might have will be addressed subsequently.

Methods Collected data will be entered in an electronic platform provided by Health Austria (https://goeg.at/) which has long-term experience in conducting and maintaining nation-wide registries, e.g. the Austrian Stroke Registry.

Non interventional study - The decision for therapy with an anti-CGRP monoclonal antibody/ CGRP antagonist is made by the treating physician and is NOT part of the Study. The study was approved by the relevant ethics committees and registered at a platform of the Austrian Agency for Health an Nutrition Safety at https://forms.ages.at/nis/. All patients treated in the headache centers are keeping headache diaries on paper or in electronic form as a standard of care procedure. Prospective and retrospective data collection from electronic charts is possible. Data are collected during routine visits which are scheduled in 3 months intervals. Collected data will be entered in an electronic platform provided by Health Austria (https://goeg.at/) in an anonymized form.

Study funding: Scientific reports concerning fremanezumab will be provideded to TEVA Austria, reports on erenumab to Novartis Austria and on galcanezumab to Eli Lilly Austria, based on financial compensation agreements.

Eligibility criteria: Inclusion Criteria (all of the follwing)

* episodic or chronic migraine with or without aura
* erenumab, fremanezumab or galcanezumab is prescribed as a standard of care treatment by treating physician Eptinezumab may be included as soon as available in Austria.

Exclusion Criteria:

• Off label use of erenumab, fremanezumab or galcanezumab

Primary outcomes:
measure: Change in Migraine days per month (= 4 weeks) from baseline to month 6
timeFrame: 6 months
Secondary outcomes:
measure: Change in headache days per month (= 4 weeks) from baseline to month 6
timeFrame: 6 months
measure: Change in aura days per month (= 4 weeks) from baseline to month 6
timeFrame: 6 months
measure: Change in days with acute headache medication per month (= 4 weeks) from baseline to month 6
timeFrame: 6 months
measure: Change in days with triptans per month (= 4 weeks) from baseline to month 6
timeFrame: 6 months
measure: Change in headache intensity from baseline to month 6
timeFrame: 6 months
measure: Change in unpleasantness of aura from baseline to month 6
timeFrame: 6 months
measure: Change in migraine duration from baseline to month 6
timeFrame: 6 months
measure: Change in migraine aura duration from baseline to month 6
timeFrame: 6 months
Other outcomes:
measure: Subjective change in quality of life from baseline to month 6
timeFrame: 6 months
measure: Change in MIDAS (Migraine Diasability Assessment Questionnaire) scores from baseline to month 6
timeFrame: 6 months
measure: Change in impact of headache from baseline to month 6
timeFrame: 6 months
measure: Adverse events
timeFrame: Up to 36 months. Assessment every 3 months, may differ between study centers.
measure: Serious adverse events
timeFrame: Up to 36 months. Assessment every 3 months, may differ between study centers. Baseline refers to the 4 weeks interval before treatment start
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tirol
city: Wien
country: Austria
facility: Medizinische Universität Wien
state: Vienna
city: Vienna
country: Austria
facility: Clinic Hietzing
Study officials:
affiliation: Medical University Innbruck
name: Gregor Broessner, Prof
role: PRINCIPAL_INVESTIGATOR
References: