The Nordic Chronic Migraine Trial of CGRP monoclonal antibody and onabotulinumtoxin A dual therapy – a randomized-controlled double-blind trial (NorMig)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

6 Jun 2025 → ongoing

Decision date (initial)

2025-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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

Secondary objectives 9

1. 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.
2. 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 difference in monthly number of days with rescue medication over 12 weeks of treatment.
3. 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.
4. 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.
5. 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 total headache score per month over 12 weeks of treatment.
6. To assess the safety of dual therapy with CGRP mAbs and BTA compared to single therapy with CGRP mAbs in chronic migraine patients over 12 weeks of treatment.
7. To assess the health economic consequences of dual therapy with CGRP mAbs and BTA versus CGRP mAbs over 12 weeks of treatment
8. To assess change of productivity loss over 12 weeks of treatment in the two groups
9. To assess resource use over 12 weeks of treatment in the two groups

Conditions and MedDRA coding

Chronic Migraine

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Informed and signed written consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
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 the 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 as defined in Appendix 4 of the protocol.

Exclusion criteria 11

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 oftime >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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction of Monthly Migraine Days (MMDs) over 12 weeks of treatment with the study medication

Secondary endpoints 20

1. Reduction of Monthly Headache Days (MHDs) over 12 weeks of treatment with the study medication
2. Monthly number of days with rescue medication over 12 weeks of treatment with the study medication.
3. Number of treatment responders (≥ 50%, ≥75% and 100 % reduction in MHD and MMDs over 12 weeks of treatment) at 12 weeks post-randomisation.
4. Number of weekly migraine days from baseline to 12 months post-randomization.
5. Total number of hours at moderate or severe pain over 12 weeks of treatment.
6. Number of treatment responders (≥ 30% reduction in mean MHDs over 12 weeks of treatment) at 12 weeks post-randomization.
7. Number of crystal-clear headache-free days after 12 weeks of treatment with the study medication.
8. Percentage of patients fulfilling the ICHD-3 diagnostic criteria for MOH over 12 weeks of treatment.
9. Number of patients completing the trial and number of dropouts.
10. Change in MIDAS over 12 weeks of treatment with the study medication.
11. Change in HADS-A and HADS-D score over 12 weeks of treatment with the study medication.
12. Change in Bergen Insomnia Scale over 12 weeks of treatment with the study medication
13. Change in Fatigue Score over 12 weeks of treatment with the study medication
14. Change in Mig-SCOG score over 12 weeks of treatment with the study medication
15. PGIC sum
16. Number of days on sick leave from baseline to 12 weeks post-randomization.
17. • Number of treatment related adverse events (AEs) and treatment related serious adverse events (SAEs) over 12 weeks of treatment.
18. Costs and Quality of life measured by EQ-5D-5L before treatment initiation, and 12 weeks after treatment initiation
19. Absenteeism from work (salary, sick leave, social security). Presenteeism (lost workplace productivity), Productivity Cost
20. Treatment duration and dose intensity for trial treatments, adverse events (eCRF). Type and frequency of physician visits, emergency departments, general practitioner visits, hospitalizations. Other related resource use, including pharmaceuticals, transport, and time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Rikshospitalet, Oslo University Hospital

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Rikshospitalet, Oslo University Hospital

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications