Hypersensitivity to CGRP as a Predictive Biomarker of Migraine Prevention With Erenumab

NCT ID: NCT04592952

Last Updated: 2022-10-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-08
• Study Completion Date: 2025-08-01

Brief Summary

To explore the relationship between clinical response to erenumab and response to intravenous infusion of calcitonin gene-related peptide in individuals with migraine.

Detailed Description

This is a single-center, non-randomized, single-arm, open-label study, in which adults with episodic or chronic migraine will receive intravenous infusion with calcitonin gene-related peptide and subsequently be treated with erenumab. The study will consist of the following elements:

• Provocation Phase (1 experimental day with intravenous infusion of calcitonin gene-related peptide)
• Screening/Baseline Phase (4 weeks)
• Open-Label Treatment Phase (24 weeks)

Conditions

Migraine

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Single-Arm

Provocation Phase: Intravenous infusion of 1.5 µg/min of calcitonin-gene related peptide over 20 minutes.

Open-Label Treatment Phase: Erenumab packed in a SureClick® Autoinjector Pen (AI)

Group Type: EXPERIMENTAL

Calcitonin Gene-Related Peptide

Intervention Type: DRUG

Intravenous infusion of 1.5 µg/min of calcitonin-gene related peptide over 20 minutes.

Erenumab

Intervention Type: DRUG

Erenumab 70 mg or 140 mg packed in a SureClick® Autoinjector Pen (AI)

Interventions

Calcitonin Gene-Related Peptide

Intravenous infusion of 1.5 µg/min of calcitonin-gene related peptide over 20 minutes.

Intervention Type: DRUG

Erenumab

Erenumab 70 mg or 140 mg packed in a SureClick® Autoinjector Pen (AI)

Intervention Type: DRUG

Other Intervention Names

CGRP; Aimovig

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years of age upon entry into screening
• History of migraine with or without aura for ≥ 12 months according to the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria
• ≥ 4 headache days that meet criteria as migraine days per month on average across the 3 months before screening
• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Must have demonstrated greater than or equal to 75% compliance in Headache Diary usage during the 4-week run-period prior to Day 1 of the open-label treatment phase.

Exclusion Criteria

• > 50 years of age at migraine onset
• History of cluster headache or hemiplegic migraine
• Inability to differentiate migraine from other headaches
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
• History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
• Previously received erenumab (Aimovig)
• Received anti-CGRP monoclonal antibody within 3 months prior to the CGRP-infusion
• Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
• Female subjects of childbearing potential with a positive pregnancy test during any study visit
• Female subject is pregnant or breastfeeding or planning to become pregnant during the study
• Evidence of current pregnancy or breastfeeding
• Female subject of childbearing potential unwilling to use an acceptable method of effective contraception
• Hypertension on the experimental day defined as systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg
• Hypotension on the experimental day defined as systolic blood pressure < 90mmHg or diastolic blood pressure < 50mmHg
• Any headache (including migraine) within 24 hours prior to the start of the CGRP-infusion
• Intake of any analgesics or migraine-specific medications within 24 hours prior to the start of the CGRP-infusion
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or comply with all required study procedures to the best of the subject and study investigator's knowledge

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Headache Center

OTHER

Sponsor Role: lead

Responsible Party

Messoud Ashina, MD

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Messoud Ashina, MD

Role: PRINCIPAL_INVESTIGATOR

Danish Headache Center

Locations

Danish Headache Center

Copenhagen, Glostrup, Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Messoud Ashina, MD

Role: CONTACT

ashina@dadlnet.dk

+4538633385

Hakan Ashina, MD

Role: CONTACT

haakan.ashina@regionh.dk

+4528102495

Facility Contacts

Hakan Ashina, MD

Role: primary

haakan.ashina@regionh.dk

Messoud Ashina, MD

Role: backup

ashina@dadlnet.dk

References

Al-Khazali HM, Ashina H, Christensen RH, Wiggers A, Rose K, Iljazi A, Amin FM, Ashina M, Snellman J, Maio-Twofoot T, Schytz HW. Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab. Cephalalgia. 2024 Jun;44(6):3331024241258734. doi: 10.1177/03331024241258734.

Reference Type: DERIVED

PMID: 38859744 (View on PubMed)

Al-Khazali HM, Ashina H, Christensen RH, Wiggers A, Rose K, Iljazi A, Schytz HW, Amin FM, Ashina M. An exploratory analysis of clinical and sociodemographic factors in CGRP-induced migraine attacks: A REFORM study. Cephalalgia. 2023 Oct;43(10):3331024231206375. doi: 10.1177/03331024231206375.

Reference Type: DERIVED

PMID: 37815254 (View on PubMed)

Al-Khazali HM, Ashina H, Wiggers A, Rose K, Iljazi A, Christensen RH, Schytz HW, Amin FM, Ashina M. Calcitonin gene-related peptide causes migraine aura. J Headache Pain. 2023 Sep 7;24(1):124. doi: 10.1186/s10194-023-01656-4.

Reference Type: DERIVED

PMID: 37679723 (View on PubMed)

Karlsson WK, Ashina H, Cullum CK, Christensen RH, Al-Khazali HM, Amin FM, Ashina M; REFORM Investigators. The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics. J Headache Pain. 2023 Jun 12;24(1):70. doi: 10.1186/s10194-023-01604-2.

Reference Type: DERIVED

PMID: 37303034 (View on PubMed)

Other Identifiers

H-20047793

Identifier Type: -

Identifier Source: org_study_id