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

NCT07040813 | Recruiting Phase 3 DMC

• 1 other identifier: EU CT number 2024-517981-40-00
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Migraine; Chronic Migraine Headache

Keywords

Migraine; CGRP; Onabotulinumtoxin A; CGRP monoclonal antibody; Combination of CGRP mAbs and onabotulinumtoxin A

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Secondary Outcomes (5)

• Change of Monthly Headache Days** over 12 weeks of treatment with the study medication

  12 weeks

• Monthly number of days with rescue medication over 12 weeks of treatment with the study medication.

  12 weeks

• 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.

  12 weeks

• Number of weekly migraine days from baseline to 12 months post-randomization.

  12 weeks

• Total number of hours at moderate or severe pain over 12 weeks of treatment.

  12 weeks

Other Outcomes (14)

• Number of treatment responders (≥ 30% reduction in mean Mean Headache Days over 12 weeks of treatment) at 12 weeks post-randomization.

  12 weeks

• Number of crystal-clear headache-free days after 12 weeks of treatment with the study medication

  12 weeks.

• Percentage of patients fulfilling the International Classification of Headache Disorders version 3 diagnostic criteria for medication overuse headache over 12 weeks of treatment.

  12 weeks

Study Arms (2)

CGRP and placebo

PLACEBO COMPARATOR

Combination of CGRP mAbs and placebo (NaCl 0.9% Braun, 0.1 ml at the same sites) in male and female participants with chronic migraine aged 18 to 70 years.

Drug: CGRP mAbs and placebo

CGRP and onabotulinumtoxin A

ACTIVE COMPARATOR

Onabotulinumtoxin A given totally 155 units at 31 sites according to modified PREEMPT or placebo (NaCl 0.9% Braun, 0.1 ml at the same sites). The treatment period is 12 weeks long.

Drug: CGRP mAbs and onabotulinumtoxin A

Interventions

CGRP mAbs and onabotulinumtoxin A DRUG

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.

CGRP and onabotulinumtoxin A

CGRP mAbs and placebo DRUG

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

CGRP and placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed and signed written consent.
• Individuals of any sex, 18-70 years at the time of signing the informed consent.
• Indications for treatment with CGRP mAbs according to SmPCs.
• Indications for treatment with BTA according to SmPC.
• No previous use of CGRP inhibitors or BTA.
• Women of childbearing potential (WOCBP) can only be included if they use a highly effective contraception method

You may not qualify if:

• 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.
• Long-standing continuous headache with no headache free days or periods for a period of time \>1 years.
• Pregnancy, planning to get pregnant, inability to use contraceptives and lactating.
• High degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator.
• Alcohol or illicit drug dependence.
• 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.
• Inability to understand study procedures and to comply with them for the entire length of the study, assessed at the discretion of the investigator.

Sponsors & Collaborators

• Oslo University Hospital: lead
• St. Olavs Hospital: collaborator
• Sykehuset Telemark: collaborator
• Sykehuset Innlandet HF: collaborator
• Sorlandet Hospital HF: collaborator
• Ostfold Hospital Trust: collaborator

Study Sites (6)

Østfold Hospital Trust

Grålum, Norway

NOT YET RECRUITING

Sørlandet Hospital Kristiansand

Kristiansand, Norway

NOT YET RECRUITING

Innlandet Hospital Trust Lillehammer

Lillehammer, Norway

NOT YET RECRUITING

Oslo University Hospital

Oslo, 0424, Norway

RECRUITING

Telemark Hospital Trust Skien

Skien, Norway

NOT YET RECRUITING

St. Olav University Hospital

Trondheim, Norway

NOT YET RECRUITING

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Related Links

• Related Info

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Central Study Contacts

Anne Hege Aamodt, Prof, MD, PhD

CONTACT

+47 95867270; a.h.aamodt@medisin.uio.no

Burcu Bezgal, Neurologist PhD student

CONTACT

+47 471 51 876‬; burbez@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Unblinded study personnel will prepare the BTA/placebo with NaCl that will be administered to the participants by blinded study personnel. BTA/placebo with NaCl will be administered at 31 predefined injection sites (5 units per injection; 155 units in total), in accordance with a modified version of the protocol from the Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1, PREEMPT. To secure the blinding in the study, the four injections in the forehead will be placed in the upper frontal region whereas the injections in corrugator and procerus are kept.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A randomized placebo-controlled double-blind phase III two-arm study.

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: June 27, 2025
• Study Start: June 6, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

NO (6)