Migraine is characterized by attacks of throbbing, moderate or severe headache, often associated with nausea, vomiting, and/or sensitivity to light and/or sound.
Chronic migraine, which occurs in 1-2 % of the population is characterized by 15 or more headache days/month for more than 3 months and at least 8 days/month with features of migraine headache.
The study will evaluate the efficacy of onabotulinumtoxin A when added to CGRP monoclonal antibody therapy in chronic migraine prevention. Adverse events and change in disease activity will be monitored.
Onabotulinumtoxin A and CGRP monoclonal antibody therapy are investigational drugs developed to prevent chronic migraine. Approximately 450 patients will be included from sites in Norway.
All participants will receive CGRP monoclonal antibody therapy. Additionally, the participants will be randomized to receive onabotulinumtoxin A or placebo injections.
Total study duration is 20 weeks including 3 on site visits and 3 telephone visits. After an inclusion visit the participants are registering data in an electronic headache diary using the application Brain Twin for a minimum of 4 weeks before the come to the randomization visit and the study medications are started. The duration of treatment is 12 weeks.
Informed and signed written consent.
Individuals of any sex, 18-70 years at the time of signing the informed consent.
Fulfilling the diagnosis chronic migraine criteria 1.3. according to the International Classification of Headache Disorders version 3 at time of inclusion.
Indications for treatment with CGRP mAbs according to SmPCs.
Contraindications, allergy or hypersensitivity reactions to BTA including infection at the injection site.
Contraindications, allergy or hypersensitivity reactions to CGRP mAbs including serious cardiovascular illness such as myocardial infarction, stroke, unstable angina pectoris, revascularization procedures last 12 months.
Concomitant medication overuse headache where drug withdrawal has not been done.
Subject is unable to differentiate migraine from other concomitant headaches.
Parallel
CGRP mAbs and onabotulinumtoxin A
DrugCGRP mAbs given subcutanously every 4th week and onabotulinumtoxin A 155 given once intramuscularly according to adjusted PREEMPT protocol in the 12 week period of study intervention.
CGRP mAbs and placebo
DrugCGRP mAbs given subcutanously every 4th week and placebo once intramuscularly according to adjusted PREEMPT protocol in the 12 week period of study
Changer of Monthly Migraine Days over 12 weeks of treatment with the study medication.
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by reduction of Monthly Migraine Days (MMDs) over 12 weeks of treatment by using headache diary with the mobile application Brain Twin until assessment at Visit 3 - primary endpoint visit.
Change of Monthly Headache Days** over 12 weeks of treatment with the study medication
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by reduction of Monthly Headache Days (MHDs) over 12 weeks of treatment by using headache diary with the mobile application Brain Twin until assessment at Visit 3.
Monthly number of days with rescue medication over 12 weeks of treatment with the study medication.
Headache diary (by using the mobile application Brain Twin) where all rescue medication is registered until Visit 3.
Number of treatment responders (≥ 50%, ≥75% and 100 % reduction in Monthly Migraine Headache days in each group over 12 weeks of treatment) at 12 weeks post-randomization.
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by number of treatment responders ≥ 50%, ≥75% and 100 % reduction in MHD and MMDs over 12 weeks of treatment by using headache diary with the mobile application Brain Twin until assessment at Visit 3.
Number of weekly migraine days from baseline to 12 months post-randomization.
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by weekly migraine days over 12 weeks of treatment by using headache diary with the mobile application Brain Twin until assessment at Visit 3.
Number of treatment responders (≥ 30% reduction in mean Mean Headache Days over 12 weeks of treatment) at 12 weeks post-randomization.
To assess the difference in number of treatment responders of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by difference in number of treatment responders over 12 weeks of treatment by using headache diary with the mobile application Brain Twin until assessment at Visit 3.
Number of crystal-clear headache-free days after 12 weeks of treatment with the study medication
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by number of crystal-clear headache-free days over 12 weeks of treatment using headache diary with the mobile application Brain Twin until assessment at Visit 3.
Percentage of patients fulfilling the International Classification of Headache Disorders version 3 diagnostic criteria for medication overuse headache over 12 weeks of treatment.
To assess the efficacy of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients measured by change in percentage of patients fulfilling the ICHD-3 diagnostic criteria for MOH over 12 weeks of treatment. This assessment is based on information registered in the headache diary during 12 weeks and assessment at Visit 3.
Number of patients completing the trial and number of dropouts
To assess the feasibility of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients over 12 weeks of treatment. This is assessed at Visit 3.
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Oslo University Hospital
Lead sponsor
St. Olavs Hospital
Collaborator
Sykehuset Telemark
Collaborator
Sykehuset Innlandet HF
Collaborator
Sorlandet Hospital HF
Collaborator
Ostfold Hospital Trust
Collaborator
