EPTINEZUMAB for Migraine

Inclusion criteria

• {"criterion_text":"- Individuals aged ≥ 18 years"}
• {"criterion_text":"- Healthy controls aged ≥ 18 years"}
• {"criterion_text":"- Healthy controls right-handedness"}
• {"criterion_text":"- Healthy controls able to autonomously sign the informed consent prior to study enrolment"}
• {"criterion_text":"- Right-handedness"}
• {"criterion_text":"- Able to autonomously sign the informed consent prior to study enrolment"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Eligibility for treatment with eptinezumab according to the current reimbursement policies of the Italian Health System"}
• {"criterion_text":"- Migraine frequency of ≥8 migraine days per month on average across the three months prior to study enrolment"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Migraine-related disability as moderate or severe according to the Migraine Disability Assessment (MIDAS) questionnaire"}
• {"criterion_text":"- 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"}

Exclusion criteria

• {"criterion_text":"- Needle phobia"}
• {"criterion_text":"- Age older than 50 years at migraine onset"}
• {"criterion_text":"- Unable to differentiate migraine from other headaches"}
• {"criterion_text":"- History of medication overuse headache according to the ICHD-3 criteria1"}
• {"criterion_text":"- Currently receiving more than one other prophylactic treatment for migraine"}
• {"criterion_text":"- Use of one migraine preventive treatment without a stable dosage for the last two months"}
• {"criterion_text":"- Currently using other preventive treatment targeting the CGRP pathway"}
• {"criterion_text":"- Currently using acute treatments targeting the CGRP pathway"}
• {"criterion_text":"- History of any headaches except for infrequent tension-type headache for healthy controls"}
• {"criterion_text":"- Needle phobia for healthy controls"}
• {"criterion_text":"- Cardio or cerebrovascular comorbidities, such as myocardial infarction, stroke, transient ischemic attack, unstable angina in healthy controls"}
• {"criterion_text":"- Cardio or cerebrovascular comorbidities, such as myocardial infarction, stroke, transient ischemic attack, unstable angina"}
• {"criterion_text":"- Poor controlled blood hypertension in healthy controls"}
• {"criterion_text":"- Other chronic pain disorders and neuropathic pain in healthy controls"}
• {"criterion_text":"- History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behaviour in healthy controls"}
• {"criterion_text":"- Evidence of drug or alcohol abuse or dependence within 12 months prior to study enrolment in healthy controls"}
• {"criterion_text":"- For females healthy controls, pregnancy or breastfeeding"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Poor controlled blood hypertension"}
• {"criterion_text":"- Other chronic headache conditions, such as cluster headache, hemiplegic migraine headache or persistent post-traumatic headache"}
• {"criterion_text":"- Other chronic pain disorders and neuropathic pain"}
• {"criterion_text":"- History of head trauma or seizure or major psychiatric disorders or suicidal ideation/behaviour"}
• {"criterion_text":"- Evidence of drug or alcohol abuse or dependence within 12 months prior to study enrolment"}
• {"criterion_text":"- For females, pregnancy or breastfeeding"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- 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.\n- 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\n- 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

• {"endpoint_text":"- 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;"}
• {"endpoint_text":"- 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."}
• {"endpoint_text":"- 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."}
• {"endpoint_text":"- 3. Correlations between changes in measures of central sensitization and measures of peripheral sensitization from baseline to week 12."}

Italy

Earliest CTIS Part Ii Submission Date

23-04-2025

Latest Decision Or Authorization Date

30-04-2025

Processing Time Days

7

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Ospedale San Raffaele S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"H. Lundbeck A/S e Lundbeck Italia S.p.A.","duties_or_roles":"Source of monetary support","organisation_type":""}