A Study of Eptinezumab in Participants With Migraine and Medication Overuse Headache (RESOLUTION)

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of add-on Eptinezumab Treatment to Brief Educational Intervention for the Preventive Treatment of Migraine in Patients With Dual Diagnosis of Migraine and Medication Overuse Headache

Medication overuse headache (MOH) is a type of headache caused by excessive use of acute headache or migraine medications (medications used to treat a headache or migraine once it begins). Treatment of MOH usually involves reducing the dose of or discontinuing acute medications.

Eptinezumab is a medication used for the preventive treatment of migraine in adults. The main goals of this trial are to learn whether eptinezumab helps reduce the number of days with migraine, the number of days with headache, and acute medication use in adults who have migraine and MOH.

Study Overview

• Status: Completed
• Conditions: Migraine; Medication Overuse Headache
• Intervention / Treatment: Drug: Eptinezumab; Drug: Placebo

Detailed Description

The total study duration from screening visit to safety follow-up visit is approximately 36 weeks and includes a screening period (4 weeks), a placebo-controlled period (12 weeks), an open-label period (12 weeks), and a safety follow-up period (8 weeks).

• Study Type: Interventional
• Enrollment (Actual): 608
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Southern Neurology
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hospital
• Denmark
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus Esbjerg
  • Capital
    • Glostrup Municipality, Capital, Denmark, 2600
      • Danish Headache Center
• France
  • Paris, France, 75014
    • Groupe hospitalier Paris saint Joseph
  • Paris, France, 75010
    • AP-HP - Hopital Lariboisiere
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06000
      • CHU de Nice
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13385
      • Assistance Publique Hopitaux de Marseille
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31000
      • Hôpital Pierre-Paul Riquet
  • Haute-Savoie
    • Pringy, Haute-Savoie, France, 74374
      • Centre Hospitalier Annecy Genevois - Site d'Annecy
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44800
      • CHRU Nantes
  • Nord
    • Lille, Nord, France, 59000
      • Hôpital Roger Salengro
  • Pays de la Loire Region
    • Saint-Priest-en-Jarez, Pays de la Loire Region, France, 42055
      • Centre Hospitalier Universitaire de Saint Etienne
  • Puy-de-Dôme
    • Clermont-Ferrand, Puy-de-Dôme, France, 63003
      • Centre Hospitalier Universitaire de Clermont Ferrand -58 Rue Montalembert
  • Rhône
    • Bron, Rhône, France, 69500
      • Hospices Civils de Lyon - Hôpital Pierre Wertheimer
• Georgia
  • Tbilisi, Georgia, 0186
    • Multiprofile Clinic Consilium Medulla
  • Tbilisi, Georgia, 0112
    • Ltd Israel-Georgia Medical Research Clinic Helsicore
  • Tbilisi, Georgia, 0160
    • Aversi Clinic Ltd
  • Tbilisi, Georgia, 0114
    • Pineo Medical Ecosystem
  • Tbilisi, Georgia, 0101
    • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center-Gobronidze 10
  • Tbilisi, Georgia, 0160
    • MediClubGeorgia Ltd
  • Tbilisi, Georgia, 0179
    • S. Khechinashvili University Clinic, Ltd.
• Germany
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald
  • Baden-Wurttemberg
    • Sindelfingen, Baden-Wurttemberg, Germany, 71065
      • Klinikverbund Südwest - Kliniken Sindelfingen
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 65929
      • Kopfschmerzzentrum Frankfurt
  • Lower Saxony
    • Westerstede, Lower Saxony, Germany, 26655
      • Studienzentrum Nord-West
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitätsklinikum Essen
    • Essen, North Rhine-Westphalia, Germany, 45133
      • Praxis fuer Neurologie, Spezielle Schmerztherapie und Psychotherapie
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitatsklinikum Carl Gustav Carus an der TU Dresden
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Universitatsklinikum Jena - Am Klinikum 1-Erlanger Allee 101
• Italy
  • Modena, Italy, 41100
    • Azienda Ospedaliero Universitaria Di Modena Policlinico
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone-Palermo-Piazza Delle Cliniche 2
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS
  • Abruzzo
    • Avezzano, Abruzzo, Italy, 67051
      • ASL 1 Abruzzo - PO Avezzano
  • Apulia
    • Bari, Apulia, Italy, 70124
      • Azienda Ospedaliero Universitaria Consorziale Policlinico
  • Campania
    • Napoli, Campania, Italy, 80138
      • Azienda Ospedaliera Universitaria Luigi Vanvitelli - Piazza Luigi Miraglia 2
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • IRCCS Istituto delle Scienze Neurologiche - Largo B. Nigrisoli
  • Lazio
    • Rome, Lazio, Italy, 00163
      • IRCCS San Raffaele
    • Rome, Lazio, Italy, 00128
      • Fondazione Policlinico Universitario Campus Bio-medico
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli - Rome - PPDS
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Milan, Lombardy, Italy, 20127
      • Ospedale San Raffaele S.r.l. - PPDS
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliera Universitaria Careggi
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • Azienda Ospedaliera di Perugia - Ospedale Santa Maria della Misericordia
• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum
• Norway
  • Oslo, Norway
    • Oslo Universitetssykehus
  • Akershus
    • Nordbyhagen, Akershus, Norway, 1474
      • Akershus Universitetssykehus
  • Hordaland
    • Bergen, Hordaland, Norway, 5021
      • Haukeland Universitetssykehus
  • Sør-Trøndelag
    • Trondheim, Sør-Trøndelag, Norway, 7006
      • St. Olav's University Hospital
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario Dr. Balmis
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro - CIOCC
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio - PPDS
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Valladolid, Spain, 47010
    • Hospital Clínico Universitario de Valladolid
  • Zaragoza, Spain, 50009
    • Hospital Clínico Universitario Lozano Blesa
  • Cádiz
    • Cadiz, Cádiz, Spain, 11009
      • Hospital Puerta del Mar
  • Córdoba
    • Córdoba, Córdoba, Spain, 14004
      • C.H. Regional Reina Sofia - PPDS
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
• Sweden
  • Halland County
    • Halmstad, Halland County, Sweden, 301 85
      • Hallands sjukhus Halmstad
  • Skåne County
    • Lund, Skåne County, Sweden, 227 33
      • Skåneuro Privatmottagning
  • Stockholm County
    • Huddinge, Stockholm County, Sweden, 141 52
      • Karolinska Universitetssjukhuset Huddinge
    • Solna, Stockholm County, Sweden, 176 64
      • CTC Clinical Trial Consultants AB
• United States
  • Florida
    • Winter Haven, Florida, United States, 33880-3053
      • Clinical Research of Central Florida - ClinEdge - PPDS
  • Louisiana
    • Marrero, Louisiana, United States, 70072-3083
      • Legacy Clinical Solutions: Tandem Clinical Research LLC - Medical Center - Marrero - ClinEdge - PPDS
  • Missouri
    • Springfield, Missouri, United States, 65807-6012
      • Clinvest - National Ave - Headlands - PPDS
  • New York
    • Amherst, New York, United States, 14226-1727
      • Dent Neurologic Institute - Amherst
    • The Bronx, New York, United States, 10461-2732
      • Headache Center - Montefiore Medical Center - BRANY - PPDS
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant has a diagnosis of migraine or MOH as defined by IHS ICHD-3 guidelines confirmed at the Screening Visit.
• The participant has ≥8 migraine days per month for each month within the past 3 months prior to the Screening Visit.
• The participant has ≥15 headache days per month for each month within the past 3 months prior to the Screening Visit.
• The participant has had an onset of migraine diagnosis at ≤50 years of age.

Exclusion Criteria:

• The participant has confounding and clinically significant pain syndromes (for example, fibromyalgia, chronic low back pain, and complex regional pain syndrome).
• The participant has a diagnosis of acute or active temporomandibular disorders.
• The participant has a history or diagnosis of chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), recurrent painful ophthalmoplegic neuropathy, migraine with brainstem aura, and migraine with neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or long duration).
• The participant has psychosis, bipolar mania, dementia, or any other psychiatric conditions whose symptoms are not controlled or who has not been adequately treated for a minimum of 6 months prior to the Screening Visit.
• The participant has a history of clinically significant cardiovascular disease including uncontrolled hypertension, vascular ischaemia, or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism).

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eptinezumab; Participants will receive an intravenous (IV) infusion of eptinezumab at Week 0 and Week 12.	Drug: Eptinezumab; Solution for infusion
Placebo Comparator: Placebo; Participants will receive a single IV infusion of matching placebo to eptinezumab at Week 0. Then, all participants will receive a single IV infusion of eptinezumab at Week 12.	Drug: Eptinezumab; Solution for infusion; Drug: Placebo; Solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo-controlled Period: Change From Baseline in the Number of MMDs at Weeks 1 - 4	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline, Weeks 1 - 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placebo-controlled Period: Change From Baseline in MMDs at Weeks 1 to 12	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline, Weeks 1 - 12
Placebo-controlled Period: Change From Baseline in the Number of Monthly Headache Days (MHDs) at Weeks 1 to 4 and Weeks 1 to 12	A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).	Baseline, Weeks 1 - 4 and Weeks 1 - 12
Placebo-controlled Period: Percentage of Participants Not Fulfilling the International Classification of Headache Disorders, 3rd Edition (ICHD-3) Diagnostic Criteria for Chronic Migraine (CM) Nor Medication Overuse Headache (MOH)	CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis. MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.	Weeks 1 - 4 and Weeks 1 - 12
Placebo-controlled Period: Change From Baseline in Average Daily Pain Assessment Score at Weeks 1 to 2	Daily Pain assessment data were collected in the headache electronic diary (eDiary) via the question "What was the worst pain intensity of this headache today?". The pain intensity assessment was collected on a 3-point scale: Mild (score = 1), Moderate (score = 2), and Severe (score = 3). For each day, the Daily Pain assessment score was derived by averaging the worst pain intensity over all headaches of that day. For days on which no headaches took place during the relevant period, the Daily Pain score was given as a score of 0. The average Daily Pain score was calculated using the Daily Pain assessments collected during Weeks 1-2.	Baseline, Weeks 1 - 2
Placebo-controlled Period: Change From Baseline in Monthly Days With Acute Migraine Medication Use at Weeks 1 to 4 and Weeks 1 to 12	Acute migraine medication included those medications classified as opioid, barbiturates, ergotamine, triptan, non-opioid analgesic, and combination of analgesic ingredients.	Baseline, Weeks 1 - 4 and Weeks 1 - 12
Open-label Period: Change From Baseline in MMDs at Weeks 13-16, 17-20, and 21-24	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline, Weeks 13-16, 17-20, and 21-24
Open-label Period: Change From Baseline in the Number of MHDs at Weeks 13-16, 17-20, and 21-24	A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).	Baseline, at Weeks 13-16, 17-20, and 21-24
Open-label Period: Percentage of Participants Not Fulfilling the ICHD-3 Diagnostic Criteria for CM Nor MOH at Weeks 13 to 24	CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis. MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.	Weeks 13 - 24
Open-label Period: Change From Baseline in Average Daily Pain Assessment Score at Weeks 13-16, 17-20, and 21-24	Daily Pain assessment data were collected in the headache eDiary via the question "What was the worst pain intensity of this headache today?". The pain intensity assessment was collected on a 3-point scale: Mild (score = 1), Moderate (score = 2), and Severe (score = 3). For each day, the Daily Pain assessment score was derived by averaging the worst pain intensity over all headaches of that day. For days on which no headaches took place during the relevant period, the Daily Pain score was given as a score of 0. The average Daily Pain score was calculated using the Daily Pain assessments collected during Weeks 13-16, 17-20, and 21-24.	Baseline, Weeks 13-16, 17-20, and 21-24
Open-label Period: Change From Baseline in Monthly Days With Acute Migraine Medication Use at Weeks 13-16, 17-20, and 21-24	Acute migraine medication included paracetamol, triptans, ergotamine, combination of non-opioid analgesics, individual non-opioid analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). Barbiturates and/or opioid analgesics were allowed when considered medically indicated providing its use does not exceed 4 days per month.	Baseline, Weeks 13-16, 17-20, and 21-24
Placebo-controlled Period: Percentage of Participants Not Fulfilling the ICHD-3 Diagnostic Criteria for CM at Weeks 1 to 4 and Weeks 1 to 12	CM: - Headache on ≥15 days/month for >3 months. - Participants had experienced ≥5 attacks that fulfilled the criteria for either migraine without aura or with aura. - On ≥8 days/month for >3 months, headache meeting the criteria for either: Migraine without aura (headache with ≥2 of these features: unilateral location, pulsating quality, moderate to severe pain, or aggravation by physical activity; plus either nausea/vomiting or photophobia/phonophobia); Migraine with aura (headache preceded or accompanied by transient focal neurological symptoms, such as visual or sensory disturbances); or headache believed to be migraine by participant and relieved by a triptan or ergot derivative. - Not better accounted for by another ICHD-3 diagnosis.	Weeks 1 - 4 and Weeks 1 - 12
Placebo-controlled Period: Percentage of Participants Not Fulfilling the ICHD-3 Diagnostic Criteria for MOH at Weeks 1 to 4 and Weeks 1 to 12	MOH: Headache occurring on ≥15 days/month with a pre-existing headache. - Regular overuse for >3 months of ≥1 drug that can be taken for acute and/or symptomatic treatment of headache. - Not better accounted for by another ICHD-3 diagnosis.	Weeks 1 - 4 and Weeks 1 - 12
Placebo-controlled Period: Change From Baseline in MMDs With Use of Acute Headache Medication at Weeks 1 to 12	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline, Weeks 1 - 12
Placebo-controlled Period: Change From Baseline in Monthly Days With Triptan or Ergotamine Medication Use at Weeks 1 to 12		Baseline, Weeks 1 - 12
Open-label Period: Change From Baseline in Monthly Days With Triptan or Ergotamine Medication Use at Weeks 13-16, 17-20, and 21-24		Baseline, Weeks 13-16, 17-20, and 21-24
Placebo-controlled Period: Change From Baseline in Monthly Days With Individual Non-opioid Analgesics or Non-steroidal Anti-inflammatory Drug (NSAID) Medication Use at Weeks 1 to 12		Baseline, Weeks 1 - 12
Open-label Period: Change From Baseline in Monthly Days With Individual Non-opioid Analgesics or NSAID Medication Use at Weeks 13-16, 17-20, and 21-24		Baseline, Weeks 13-16, 17-20, and 21-24
Placebo-controlled Period: Change From Baseline in Monthly Days With Combination Non-opioid Analgesics Medication Use at Weeks 1 to 12		Baseline, Weeks 1 - 12
Placebo-controlled Period: Number of Participants With Migraine on the Day After Dosing		Day 1
Placebo-controlled Period: Percentage of Participants With ≥50% Reduction From Baseline in MMDs at Weeks 1 to 4 and Weeks 1 to 12	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Percentage of Participants With ≥75% Reduction From Baseline in MMDs at Weeks 1 to 4 and Weeks 1 to 12	A Migraine Day was defined as a day with a headache if it belonged to any subgroup of headaches that: lasted ≥30 minutes and met following 2 criteria: - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; lasted ≥30 minutes and participant had an aura with headache.; lasted ≥30 minutes and met 2 of following 3 criteria: - lasted 4 hours; - ≥2 of following characteristics: unilateral location; pulsating quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity; - During headache participant had ≥1 of following: nausea, vomiting, photophobia and phonophobia.; A day with a headache that was successfully treated with a migraine specific treatment.; A day with an aura without a headache with medication taken.	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Percentage of Participants With ≥50% Reduction From Baseline in MHDs at Weeks 1 to 4 and Weeks 1 to 12	A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Percentage of Participants With ≥75% Reduction From Baseline in MHDs at Weeks 1 to 4 and Weeks 1 to 12	A headache day was defined as a day with a headache that lasted ≥30 minutes or that met the definition of a migraine day (as defined in outcome measure 1).	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Change From Baseline in Percentage of Migraine Attacks With Severe Pain Intensity at Weeks 1 to 4 and Weeks 1 to 12	A migraine that fulfilled the criteria for a migraine, was referred to as a migraine attack.	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Change From Baseline in Percentages of Headache Episodes With Severe Pain Intensity at Weeks 1 to 4 and Weeks 1 to 12	A non-migraine headache that lasted ≥30 minutes or a migraine headache, was referred to as a headache episode.	Baseline to Weeks 1 - 4 and 1 - 12
Placebo-controlled Period: Patient Global Impression of Change (PGIC) Score at Weeks 4 and 12	The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.	Weeks 4 and 12
Open-label Period: PGIC Score at Week 24	The PGIC is a single, participant-reported item reflecting the participant's impression of change in his/her disease status since the start of the study (that is, in relation to activity limitations, symptoms, emotions, and overall quality of life). Participants rated their impression of change in disease status on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a higher score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.	Week 24
Placebo-controlled Period: Most Bothersome Symptom (MBS) Score at Week 12	Participants were asked about their most bothersome symptom associated with their migraines during the Baseline Visit. Participants were asked to rate the improvement in this symptom from baseline on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a high score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. The MBS areas included: nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, and other symptoms.	Week 12
Open-label Period: MBS Score at Week 24	Participants were asked about their most bothersome symptom associated with their migraines during the Baseline Visit. Participants were asked to rate the improvement in this symptom from baseline on a 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) where a high score indicated worsening. Score ranges from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. The MBS areas included: nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, and other symptoms.	Week 24
Placebo-controlled Period: Change From Baseline in Headache Impact Test (HIT-6) Total Score at Weeks 4 and 12	The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49).	Baseline, Weeks 4 and 12
Open-label Period: Change From Baseline in HIT-6 Total Score at Week 24	The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤49).	Week 24
Placebo-controlled Period: Change From Baseline in Modified Migraine Disability Assessment (mMIDAS) Total Score at Weeks 4 and 12	The mMIDAS is a self-administered questionnaire that contains 7 questions about the headache a participant had in the previous month. The first 5 questions assess the impact of migraine on 3 domains of daily activity: 2 questions for paid work or schoolwork, 2 questions for household work, and 1 question for family, social and leisure activities. The 2 questions for each of the first two groups assess, respectively, the number of days off due to headache, and the number of days in which the productivity was reduced by half or more. mMIDAS total score was derived from the sum of the answers on the first 5 questions. Total score ranged from 0 (little/no disability) to 20 (severe disability) with higher scores indicating more severe disability.	Baseline, Weeks 4 and 12
Open-label Period: Change From Baseline in mMIDAS Total Score at Week 24	The mMIDAS is a self-administered questionnaire that contains 7 questions about the headache a participant had in the previous month. The first 5 questions assess the impact of migraine on 3 domains of daily activity: 2 questions for paid work or schoolwork, 2 questions for household work, and 1 question for family, social and leisure activities. The 2 questions for each of the first two groups assess, respectively, the number of days off due to headache, and the number of days in which the productivity was reduced by half or more. mMIDAS total score was derived from the sum of the answers on the first 5 questions. Total score ranged from 0 (little/no disability) to 20 (severe disability) with higher scores indicating more severe disability.	Baseline, Week 24
Placebo-controlled Period: Change From Baseline in Migraine-Specific Quality of Life Questionnaire, Version 2.1 (MSQ v2.1) Subscores (Role Function-Restrictive, Role Function-Preventive, Emotional Function) at Weeks 4 and 12	The MSQ v2.1 is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0-to-100-point scale. Higher scores indicated better quality of life.	Baseline, Weeks 4 and 12
Open-label Period: Change From Baseline in MSQ v2.1 Subscores (Role Function-Restrictive, Role Function-Preventive, Emotional Function) at Week 24	The MSQ v2.1 is a participant-reported outcome designed to assess the quality of life in participants with migraine. It consists of 14 items covering 3 domains: role function restrictive (7 items); role function preventive (4 items); and emotional function (3 items). Each item was scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores were summed and transformed to a 0-to-100-point scale. Higher scores indicated better quality of life.	Baseline, Weeks 24
Placebo-controlled Period: Change From Baseline in Euroqol 5 Dimension - 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Weeks 4 and 12	The EQ-5D-5L VAS measures participant's self-rated health-related quality of life on a VAS. The VAS score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline, Weeks 4 and 12
Open-label Period: Change From Baseline in EQ-5D-5L VAS Score at Week 24	The EQ-5D-5L VAS measures participant's self-rated health-related quality of life on a VAS. The VAS score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).	Week 24
Placebo-controlled Period: Change From Baseline in Work Productivity and Activity Impairment: Migraine (WPAI:M) Sub-scores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Week 12	The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.	Baseline, Week 12
Open-label Period: Change From Baseline in WPAI:M Sub-scores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Week 24	The WPAI Questionnaire is a participant-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores were calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores were calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.	Baseline, Week 24
Placebo-controlled Period: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale (Depression and Anxiety) Scores at Weeks 4 and 12	The HADS is a participant-rated scale designed to assess psychological distress in non-psychiatric participants. The HADS consists of 2 sub-scales: depression and anxiety. Each sub-scale contains 7 items, and each item was rated from 0 (absent) to 3 (maximum severity). The total score of each sub-scale ranged from 0 (absent) to 21 (maximum severity). Higher scores indicated higher severity.	Baseline, Weeks 4 and 12
Open-label Period: Change From Baseline in HADS Subscale (Depression and Anxiety) Scores at Week 24	The HADS is a participant-rated scale designed to assess psychological distress in non-psychiatric participants. The HADS consists of 2 sub-scales: depression and anxiety. Each sub-scale contains 7 items, and each item was rated from 0 (absent) to 3 (maximum severity). The total score of each sub-scale ranged from 0 (absent) to 21 (maximum severity). Higher scores indicated higher severity.	Baseline, Week 24
Placebo-controlled Period: Treatment Satisfaction Questionnaire for Medicine - 9 Items (TSQM-9) Score at Weeks 4 and 12	TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.	Weeks 4 and 12
Open-label Period: TSQM-9 Score at Week 24	TSQM is a 14-item instrument consisting of four scales: effectiveness scale (questions 1 to 3), side effects scale (questions 4 to 8), convenience scale (questions 9 to 11) and global satisfaction scale (questions 12 to 14). In TSQM-9, the five items related to side effects of medication were not included. The scores were computed by adding items for each domain. The lowest possible score was subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.	Baseline, Week 24
Placebo-controlled Period: Migraine Specific Health Care Resource Utilization (HCRU) - Visits to a Family Doctor/General Practitioner at Baseline and Week 12	Number of participants who visited to a family doctor/general practitioner during the past 4 weeks has been reported at Baseline and Week 12.	Baseline and Week 12
Placebo-controlled Period: Migraine Specific HCRU - Visits to a Specialist at Baseline and Week 12	Number of participants who visited a specialist during the past 4 weeks has been reported at Baseline and Week 12.	Baseline and Week 12
Placebo-controlled Period: Migraine Specific HCRU - Number of Emergency Department Visits Due to Migraine at Baseline and Week 12	Number of participants who visited to the emergency department due to migraine during the past 4 weeks has been reported at Baseline and Week 12.	Baseline and Week 12
Placebo-controlled Period: Migraine Specific HCRU - Number of Hospital Admissions Migraine at Baseline and Week 12	Number of participants who were admitted to the hospital during the past 4 weeks due to migraine has been reported at Baseline and Week 12.	Baseline and Week 12
Placebo-controlled Period: Migraine Specific HCRU - Total Number of Participants With Overnight Hospital Stays Due to Migraine at Baseline and Week 12	Number of participants who had overnight hospital stays during the past 4 weeks due to migraine has been reported at Baseline and Week 12.	Baseline and Week 12
Open-label Period: Migraine Specific HCRU - Visits to a Family Doctor/General Practitioner at Week 24	Number of participants who visited a family doctor/general practitioner has been reported.	Week 24
Open-label Period: Migraine Specific HCRU - Visits to a Specialist at Week 24	Number of participants who visited a specialist has been reported.	Week 24
Open-label Period: Migraine Specific HCRU - Number of Participants With Emergency Department Visits Due to Migraine at Week 24	Number of participants who visited the emergency department due to migraine has been reported.	Week 24
Open-label Period: Migraine Specific HCRU - Number of Participants With Hospital Admissions Due to Migraine at Week 24	Number of participants who admitted in the hospital due to migraine has been reported.	Week 24
Open-label Period: Migraine Specific HCRU - Number of Participants With Overnight Hospital Stays Due to Migraine at Week 24	Number of participants with overnight hospital stays due to migraine has been reported.	Week 24

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Investigators: Study Director: Email contact via H. Lundbeck A/S, HQ_Medinfo@Lundbeck.com

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): October 22, 2024
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Migraine; Eptinezumab; Medication overuse headache; Brief educational intervention
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache Disorders, Secondary; eptinezumab
• Other Study ID Numbers: 20007A; 2021-003049-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No