Monoclonal CGRP Antibodies for Migraine Prevention - a Nationwide Real Life Study

Non-interventional Study of the Austrian Headache Society: Monoclonal CGRP Antibodies for Migraine Prevention a Nationwide Real Life Study

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine; Chronic Migraine; Migraine Without Aura; Migraine With Aura; Episodic Migraine
• Intervention / Treatment: Drug: Erenumab; Drug: Galcanezumab; Drug: Fremanezumab

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.

• Study Type: Observational
• Enrollment (Anticipated): 1500

Contacts and Locations

• Study Contact: Name: Franz Riederer, Prof; Phone Number: +436803279153; Email: franz.riederer@uzh.ch
• Study Contact Backup: Name: Karin Zebenholzer, Prof; Phone Number: +43140400; Email: karin.zebenholzer@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, A1130
    • Recruiting
    • Clinic Hietzing
    • Contact: Stefan Hubmer, MD; Phone Number: +431801100; Email: stefan.hubmer@gesundheitsverbund.at
    • Contact: Franz Riederer, Prof.; Phone Number: +436803279153; Email: franz.riederer@uzh.ch
    • Principal Investigator: Stefan Hubmer, MD
  • Tirol
    • Innsbruck, Tirol, Austria, A6020
      • Recruiting
      • Medical University Innsbruck
      • Contact: Gregor Broessner, Prof; Phone Number: +43 512 9003 - 0; Email: gregor.broessner@i-med.ac.at
      • Principal Investigator: Gregor Broessner, gregor.broessner@i-med.ac.at
  • Vienna
    • Wien, Vienna, Austria, 1090
      • Recruiting
      • Medizinische Universität Wien
      • Contact: Zebenholzer U Karin, Prof.; Phone Number: +43140400; Email: karin.zebenholzer@meduniwien.ac.at
      • Contact: Christian Woeber, Prof.; Phone Number: +43140400; Email: christian.woeber@meduniwien.ac.at
      • Principal Investigator: Karin Zebenholzer, Prof.
      • Sub-Investigator: Christian Woeber, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Erenumab; Patients will be treated with this drug within standard of care treatment	Drug: Erenumab; treatment with erenumab as chosen by treating physician
Galcanezumab; Patients will be treated with this drug within standard of care treatment	Drug: Galcanezumab; treatment with galcanezumab as chosen by treating physician
Fremanezumab; Patients will be treated with this drug within standard of care treatment	Drug: Fremanezumab; treatment with fremanezumab as chosen by treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Migraine days per month (= 4 weeks) from baseline to month 6	Either of the following: (i) patient has treated headache with a triptan (ii) criteria C+ D for migraine without aura are fulfilled (iii) criteria B+C for migraine with aura are fulfilled	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in headache days per month (= 4 weeks) from baseline to month 6	Any day with headache	6 months
Change in aura days per month (= 4 weeks) from baseline to month 6	Any day with at least one migraine aura	6 months
Change in days with acute headache medication per month (= 4 weeks) from baseline to month 6	Any days on which medication against migraine was taken by the patient	6 months
Change in days with triptans per month (= 4 weeks) from baseline to month 6	Any days on which triptans medication were taken by the patient	6 months
Change in headache intensity from baseline to month 6	Usual intensity of headche attacks on a numerical rating scale from 1 -10. Higher numbers indicate more severe headache attacks	6 months
Change in unpleasantness of aura from baseline to month 6	Usual unpleasantness of aura on a numerical rating scale from 1 -10. Higher numbers indicate more unpleasantness.	6 months
Change in migraine duration from baseline to month 6	Usual duration of migraine headache attack	6 months
Change in migraine aura duration from baseline to month 6	Usual duration of migraine aura	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective change in quality of life from baseline to month 6	3 point scale: improved, unchanged, worse	6 months
Change in MIDAS (Migraine Diasability Assessment Questionnaire) scores from baseline to month 6	Migraine Disability Assessment Questionnaire. A higher Score indicates more disability. mnimum = 0, maximum =270	6 months
Change in impact of headache from baseline to month 6	Questionnaire. Higher scores indicate more impact of headache. Minmum= 36, maximum =38	6 months
Adverse events	Any treatment emergent adverse events, Causality according to FDA rating: unlikely, possible, probable	Up to 36 months. Assessment every 3 months, may differ between study centers.
Serious adverse events	Definiation and causality according to FDA	Up to 36 months. Assessment every 3 months, may differ between study centers. Baseline refers to the 4 weeks interval before treatment start

Collaborators and Investigators

• Sponsor: Austrian Migraine Registry Collaboration
• Collaborators: Medical University of Vienna; Medical University Innsbruck; Austrian Headache Society
• Investigators: Principal Investigator: Gregor Broessner, Prof, Medical University Innbruck

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Erenumab; Galcanezumab; Fremanezumab; CGRP-antibodies
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine without Aura; Migraine with Aura; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: EK Nr: 1122/2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No