RECRUITINGPhase 3INTERVENTIONAL

The Nordic Chronic Migraine Trial of CGRP Monoclonal Antibody and Onabotulinumtoxin A Dual Therapy Compared to CGRP mAbs Monotherapy

A Randomized Placebo-controlled Double-blind Phase III Trial to Investigate the Reduction of Monthly Migraine Days (MMDs) Over 12 Weeks of Treatment With CGRP mAbs and Onabotulinumtoxin A Intramuscularly Compared With CGRP mAbs and Placebo in Chronic Migraine

About This Trial

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.

Who May Be Eligible (Plain English)

Inclusion criteria 1. Informed and signed written consent. 2. Individuals of any sex, 18-70 years at the time of signing the willing to sign a consent form. 3. Fulfilling the diagnosis chronic migraine criteria 1.3. according to the International Classification of Headache Disorders version 3 at time of inclusion. 4. Indications for treatment with CGRP mAbs according to SmPCs. 5. Indications for treatment with BTA according to SmPC. 6. No previous use of CGRP inhibitors or BTA. 7. Women of childbearing potential (WOCBP) can only be included if they use a highly effective contraception method Who Should NOT Join This Trial: 1. Contraindications, allergy or hypersensitivity reactions to BTA including infection at the injection site. 2. 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. 3. Concomitant medication overuse headache where drug withdrawal has not been done. 4. Subject is unable to differentiate migraine from other concomitant headaches. 5. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion (Visit 2). 6. Long-standing continuous headache with no headache free days or periods for a period of time \>1 years. 7. Pregnancy, planning to get pregnant, inability to use contraceptives and lactating. 8. High degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator. 9. Alcohol or illicit drug dependence. 10. Investigators may exclude patients who, for various reasons (for example, severe psychiatric disorders), are considered unlikely to be able to complete the tasks required for participation in the study. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion criteria 1. Informed and signed written consent. 2. Individuals of any sex, 18-70 years at the time of signing the informed consent. 3. Fulfilling the diagnosis chronic migraine criteria 1.3. according to the International Classification of Headache Disorders version 3 at time of inclusion. 4. Indications for treatment with CGRP mAbs according to SmPCs. 5. Indications for treatment with BTA according to SmPC. 6. No previous use of CGRP inhibitors or BTA. 7. Women of childbearing potential (WOCBP) can only be included if they use a highly effective contraception method Exclusion criteria: 1. Contraindications, allergy or hypersensitivity reactions to BTA including infection at the injection site. 2. 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. 3. Concomitant medication overuse headache where drug withdrawal has not been done. 4. Subject is unable to differentiate migraine from other concomitant headaches. 5. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion (Visit 2). 6. Long-standing continuous headache with no headache free days or periods for a period of time \>1 years. 7. Pregnancy, planning to get pregnant, inability to use contraceptives and lactating. 8. High degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator. 9. Alcohol or illicit drug dependence. 10. Investigators may exclude patients who, for various reasons (for example, severe psychiatric disorders), are considered unlikely to be able to complete the tasks required for participation in the study. 11. Inability to understand study procedures and to comply with them for the entire length of the study, assessed at the discretion of the investigator.

Treatments Being Tested

DRUG

CGRP mAbs and onabotulinumtoxin A

CGRP 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.

DRUG

CGRP mAbs and placebo

CGRP mAbs given subcutanously every 4th week and placebo once intramuscularly according to adjusted PREEMPT protocol in the 12 week period of study

Locations (6)

Østfold Hospital Trust

Grålum, Norway

Sørlandet Hospital Kristiansand

Kristiansand, Norway

Innlandet Hospital Trust Lillehammer

Lillehammer, Norway

Oslo University Hospital

Oslo, Norway

Telemark Hospital Trust Skien

Skien, Norway

St. Olav University Hospital

Trondheim, Norway