Exploring Eptinezumab: Unveiling Peripheral and Central Mechanisms of Action and Searching for Biomarkers of Patient Response (EUPHORIA Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Jan 2026 → ongoing

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

H. Lundbeck A/S e Lundbeck Italia S.p.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

1. To identify reference values specific to migraine for measures of central and peripheral sensitization.
2. To identify treatment-induced changes in measures of central and/or peripheral sensitization, from baseline to week 12 of eptinezumab 100mg, and to explore correlation between treatment-induced changes in candidate measures of sensitization and clinical efficacy measures at 12 weeks of treatment with eptinezumab 100mg (analysis: changes intra patients treated with eptinezumab 100mg).

Secondary objectives 3

1. 1. To evaluate the impact of dose escalation from 100mg to 300mg of eptinezumab on central and peripheral sensitization and explore correlation between treatment-induced changes in candidate measures of sensitization and clinical efficacy measures at 12 weeks of treatment with eptinezumab 300mg.
2. 2. To define the profile of responders to eptinezumab through the identification of biomarkers associated with a positive response to 12 weeks of eptinezumab at 100mg, as well as biomarkers characterizing individuals with migraine who do not respond to 100mg of eptinezumab but achieve a positive response with an increased dosage to 300mg.
3. 3. To assess the association between changes in measures of central and peripheral sensitization in migraine patients.

Conditions and MedDRA coding

Migraine

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Individuals aged ≥ 18 years
2. Right-handedness
3. Able to autonomously sign the informed consent prior to study enrolment
4. History of migraine with or without aura for at least 12 months prior to study enrolment, based on the diagnostic criteria of the International Classification of Headache Disorders version 3rd edition (ICHD-3)1, as determined from medical records and/or migraine participants self-report
5. Eligibility for treatment with eptinezumab according to the current reimbursement policies of the Italian Health System
6. Migraine frequency of ≥8 migraine days per month on average across the three months prior to study enrolment
7. Failure to respond to three or more previous preventive treatments, including tricyclics, anticonvulsants, beta-blockers, and onabotulinum toxin A, due to either lack of efficacy or poor tolerability. Efficacy failure is defined as no reduction in headache and migraine frequency, duration, or severity after administering the respective medication for at least 6 weeks at approved therapeutic dose(s). Tolerability failure is defined as documented discontinuation due to adverse events of the respective medication at any time prior to screening
8. Migraine-related disability as moderate or severe according to the Migraine Disability Assessment (MIDAS) questionnaire
9. Female subjects of childbearing potential must practice at least one of the following specified method of birth control during the study: combined (estrogen and progestogen containing) hormonal birth control (oral, intravaginal, transdermal, injectable); progestogen-only hormonal birth control (oral, injectable, implantable); bilateral tubal occlusion/ligation; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; practice true abstinence, a barrier method (male condom or female condom) with or without spermicide or cap, diaphragm or sponge with spermicide
10. Healthy controls aged ≥ 18 years
11. Healthy controls right-handedness
12. Healthy controls able to autonomously sign the informed consent prior to study enrolment

Exclusion criteria 25

1. Needle phobia
2. Cardio or cerebrovascular comorbidities, such as myocardial infarction, stroke, transient ischemic attack, unstable angina
3. Poor controlled blood hypertension
4. Other chronic headache conditions, such as cluster headache, hemiplegic migraine headache or persistent post-traumatic headache
5. Other chronic pain disorders and neuropathic pain
6. History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behaviour
7. Evidence of drug or alcohol abuse or dependence within 12 months prior to study enrolment
8. For females, pregnancy or breastfeeding
9. Clinical conditions contraindicating a MRI scan, such as pacemakers, aneurysm clips, artificial heart valves, ear implants, foreign metal objects in the eyes, skin, or body, or any other condition deemed hazardous in combination with MRI
10. Age older than 50 years at migraine onset
11. Unable to differentiate migraine from other headaches
12. History of medication overuse headache according to the ICHD-3 criteria1
13. Currently receiving more than one other prophylactic treatment for migraine
14. Use of one migraine preventive treatment without a stable dosage for the last two months
15. Currently using other preventive treatment targeting the CGRP pathway
16. Currently using acute treatments targeting the CGRP pathway
17. History of any headaches except for infrequent tension-type headache for healthy controls
18. Needle phobia for healthy controls
19. Cardio or cerebrovascular comorbidities, such as myocardial infarction, stroke, transient ischemic attack, unstable angina in healthy controls
20. Poor controlled blood hypertension in healthy controls
21. Other chronic pain disorders and neuropathic pain in healthy controls
22. History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behaviour in healthy controls
23. Evidence of drug or alcohol abuse or dependence within 12 months prior to study enrolment in healthy controls
24. For females healthy controls, pregnancy or breastfeeding
25. Clinical conditions contraindicating a MRI scan, such as pacemakers, aneurysm clips, artificial heart valves, ear implants, foreign metal objects in the eyes, skin, or body, or any other condition deemed hazardous in combination with MRI, in healthy controls.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Differences between patients with migraine and healthy controls at baseline in serum levels of calcitonin gene-related peptide, transcriptomic profiles on inflammatory and pain mediators, AUC and degree of habituation of the second component of the nociceptive blink reflex, resting state (RS) functional connectivity (FC) of brain networks involved in pain processing.
2. 2a. Any of the following measures in patients showing significant changes from baseline to week 12 of eptinezumab 100mg: serum levels of CGRP, Transcriptomic profiles on inflammatory and pain mediators, AUC and degree of habituation of the second component of the nociceptive blink reflex (R2), RS FC of brain networks involved in pain processing
3. 2b. Correlation between changes in the identified candidate measure(s) of sensitization (serum CGRP levels, transcriptomic profiles, RS FC of pain processing brain networks, AUC, and degree of habituation of the R2 component of the nociceptive blink reflex) and changes in clinical efficacy measures following a 12-week treatment with eptinezumab at doses of 100mg.

Secondary endpoints 4

1. 1a. Differences in changes of any of the candidate measures of sensitization (serum CGRP levels, transcriptomic profiles, RS FC of pain processing brain networks, AUC, and degree of habituation of the R2 component of the nociceptive blink reflex), from week 12 to week 24, between patients receiving eptinezumab 100mg and those receiving eptinezumab 300mg;
2. 1b. Correlation between changes in the identified candidate measure(s) of sensitization and changes in clinical efficacy measures following a 12-week treatment with eptinezumab at doses of 300mg.
3. 2. Differences in changes of any of the candidate measures of sensitization, from baseline to week 12, between responders and non-responders to eptinezumab 100mg. We will also assess differences in changes of any of the candidate measures of sensitization, from week 12 to week 24, between responders and non-responders to eptinezumab 300mg.
4. 3. Correlations between changes in measures of central sensitization and measures of peripheral sensitization from baseline to week 12.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Massimo Filippi

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Massimo Filippi

Locations

1 EU/EEA country · 1 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 10 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