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

NCT04592952 | Unknown Phase 4

• 1 other identifier: H-20047793
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (1)

• Headache Diary (Baseline Phase and Treatment Phase)

  Headache diary with daily entries to record migraine-related data (e.g. migraine days, headache days, number of days with use of acute migraine medication, number of days with aura).

  Baseline Phase (Day -28 to Day 1) to Week 24

Secondary Outcomes (2)

• Headache Diary (Provocation Phase)

  Provocation Phase (12 Hours)

• Semi-Structured Interview

  1 Hour

Study Arms (1)

Single-Arm

EXPERIMENTAL

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)

Drug: Calcitonin Gene-Related Peptide; Drug: Erenumab

Interventions

Calcitonin Gene-Related Peptide DRUG

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

Also known as: CGRP

Single-Arm

Erenumab DRUG

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

Also known as: Aimovig

Single-Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \> 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

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Danish Headache Center

Copenhagen, Glostrup, 2600, Denmark

RECRUITING

Related Publications (4)

• 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.

  PMID: 38859744 DERIVED

• 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.

  PMID: 37815254 DERIVED

• 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.

  PMID: 37679723 DERIVED

• 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.

  PMID: 37303034 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Calcitonin Gene-Related Peptide; erenumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Messoud Ashina, MD

  Danish Headache Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Messoud Ashina, MD

CONTACT

+4538633385; ashina@dadlnet.dk

Hakan Ashina, MD

CONTACT

+4528102495; haakan.ashina@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 19, 2020
• Study Start: October 8, 2020
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: October 24, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)