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Phase 4 N=608 Randomized Double-blind Prevention

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

Migraine · Medication Overuse Headache

Enrolled (actual)
608
Serious AEs
0.8%
Results posted
Dec 2025
Primary outcome: Primary: Placebo-controlled Period: Change From Baseline in the Number of MMDs at Weeks 1 - 4 — -6.85; -3.66 days/month — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Eptinezumab (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
H. Lundbeck A/S
Primary completion
Oct 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Placebo-controlled Period: Change From Baseline in the Number of MMDs at Weeks 1 - 4
-6.85; -3.66 <0.0001 sig
SECONDARY
Placebo-controlled Period: Change From Baseline in MMDs at Weeks 1 to 12
-7.44; -4.50 <0.0001 sig
SECONDARY
Placebo-controlled Period: Change From Baseline in the Number of Monthly Headache Days (MHDs) at Weeks 1 to 4 and Weeks 1 to 12
-6.54; -3.40; -7.38; -4.45 <0.0001 sig
SECONDARY
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)
37.8; 18.1; 27.2; 12.7 <0.0001 sig
SECONDARY
Placebo-controlled Period: Change From Baseline in Average Daily Pain Assessment Score at Weeks 1 to 2
-0.58; -0.27 <0.0001 sig
SECONDARY
Placebo-controlled Period: Change From Baseline in Monthly Days With Acute Migraine Medication Use at Weeks 1 to 4 and Weeks 1 to 12
-11.32; -7.69; -11.18; -7.83 <0.0001 sig
SECONDARY
Open-label Period: Change From Baseline in MMDs at Weeks 13-16, 17-20, and 21-24
-10.23; -10.08; -10.29; -10.29; -9.24; -9.30
SECONDARY
Open-label Period: Change From Baseline in the Number of MHDs at Weeks 13-16, 17-20, and 21-24
-10.31; -9.99; -10.46; -10.34; -9.46; -9.47
SECONDARY
Open-label Period: Percentage of Participants Not Fulfilling the ICHD-3 Diagnostic Criteria for CM Nor MOH at Weeks 13 to 24
38.9; 40.2
SECONDARY
Open-label Period: Change From Baseline in Average Daily Pain Assessment Score at Weeks 13-16, 17-20, and 21-24
-0.90; -0.90; -0.88; -0.89; -0.84; -0.81
SECONDARY
Open-label Period: Change From Baseline in Monthly Days With Acute Migraine Medication Use at Weeks 13-16, 17-20, and 21-24
-12.08; -11.67; -11.82; -11.39; -10.96; -10.44
SECONDARY
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
55.0; 32.4; 44.4; 23.0
SECONDARY
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
52.2; 31.9; 40.1; 24.0
SECONDARY
Placebo-controlled Period: Change From Baseline in MMDs With Use of Acute Headache Medication at Weeks 1 to 12
-10.32; -7.16
SECONDARY
Placebo-controlled Period: Change From Baseline in Monthly Days With Triptan or Ergotamine Medication Use at Weeks 1 to 12
-8.35; -5.49
SECONDARY
Open-label Period: Change From Baseline in Monthly Days With Triptan or Ergotamine Medication Use at Weeks 13-16, 17-20, and 21-24
-8.70; -8.79; -8.24; -8.31; -7.43; -7.56
SECONDARY
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
-5.94; -4.80
SECONDARY
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
-6.55; -6.66; -6.65; -6.62; -6.18; -6.44
SECONDARY
Placebo-controlled Period: Change From Baseline in Monthly Days With Combination Non-opioid Analgesics Medication Use at Weeks 1 to 12
-1.24; -1.12
SECONDARY
Placebo-controlled Period: Number of Participants With Migraine on the Day After Dosing
162; 203
SECONDARY
Placebo-controlled Period: Percentage of Participants With ≥50% Reduction From Baseline in MMDs at Weeks 1 to 4 and Weeks 1 to 12
36.7; 13.7; 40.4; 18.0
SECONDARY
Placebo-controlled Period: Percentage of Participants With ≥75% Reduction From Baseline in MMDs at Weeks 1 to 4 and Weeks 1 to 12
13.0; 4.3; 12.9; 5.3
SECONDARY
Placebo-controlled Period: Percentage of Participants With ≥50% Reduction From Baseline in MHDs at Weeks 1 to 4 and Weeks 1 to 12
33.0; 11.0; 35.8; 15.3
SECONDARY
Placebo-controlled Period: Percentage of Participants With ≥75% Reduction From Baseline in MHDs at Weeks 1 to 4 and Weeks 1 to 12
9.3; 3.3; 10.9; 5.3
SECONDARY
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
-10.30; -1.60; -5.21; -1.60
SECONDARY
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
-11.78; -3.36; -6.99; -2.79
SECONDARY
Placebo-controlled Period: Patient Global Impression of Change (PGIC) Score at Weeks 4 and 12
2.62; 3.63; 2.64; 3.54
SECONDARY
Open-label Period: PGIC Score at Week 24
2.3; 2.3
SECONDARY
Placebo-controlled Period: Most Bothersome Symptom (MBS) Score at Week 12
2.87; 3.59
SECONDARY
Open-label Period: MBS Score at Week 24
2.6; 2.6
SECONDARY
Placebo-controlled Period: Change From Baseline in Headache Impact Test (HIT-6) Total Score at Weeks 4 and 12
-6.5; -2.6; -7.4; -3.9
SECONDARY
Open-label Period: Change From Baseline in HIT-6 Total Score at Week 24
-8.1; -7.6
SECONDARY
Placebo-controlled Period: Change From Baseline in Modified Migraine Disability Assessment (mMIDAS) Total Score at Weeks 4 and 12
-14.73; -6.62; -13.83; -8.76
SECONDARY
Open-label Period: Change From Baseline in mMIDAS Total Score at Week 24
-17.3; -15.2
SECONDARY
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
24.04; 10.15; 22.55; 11.79; 18.58; 7.88
SECONDARY
Open-label Period: Change From Baseline in MSQ v2.1 Subscores (Role Function-Restrictive, Role Function-Preventive, Emotional Function) at Week 24
26.38; 26.33; 20.6; 20.7; 26.86; 26.54
SECONDARY
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
5.09; 0.49; 7.43; 2.23
SECONDARY
Open-label Period: Change From Baseline in EQ-5D-5L VAS Score at Week 24
5.9; 3.9
SECONDARY
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
-4.73; -1.18; -19.10; -10.12; -19.88; -9.04
SECONDARY
Open-label Period: Change From Baseline in WPAI:M Sub-scores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Week 24
-9.22; -4.75; -18.8; -22.7; -20.54; -24.18
SECONDARY
Placebo-controlled Period: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale (Depression and Anxiety) Scores at Weeks 4 and 12
-1.59; -0.61; -1.82; -0.64; -1.32; -0.49
SECONDARY
Open-label Period: Change From Baseline in HADS Subscale (Depression and Anxiety) Scores at Week 24
-2.1; -1.3; -2.0; -1.1
SECONDARY
Placebo-controlled Period: Treatment Satisfaction Questionnaire for Medicine - 9 Items (TSQM-9) Score at Weeks 4 and 12
58.21; 39.01; 57.95; 40.89; 69.60; 63.62
SECONDARY
Open-label Period: TSQM-9 Score at Week 24
63.23; 62.50; 66.23; 66.02; 64.23; 63.51
SECONDARY
Placebo-controlled Period: Migraine Specific Health Care Resource Utilization (HCRU) - Visits to a Family Doctor/General Practitioner at Baseline and Week 12
213; 198; 44; 42; 10; 17
SECONDARY
Placebo-controlled Period: Migraine Specific HCRU - Visits to a Specialist at Baseline and Week 12
180; 156; 71; 83; 21; 18
SECONDARY
Placebo-controlled Period: Migraine Specific HCRU - Number of Emergency Department Visits Due to Migraine at Baseline and Week 12
275; 256; 7; 7; 1; 3
SECONDARY
Placebo-controlled Period: Migraine Specific HCRU - Number of Hospital Admissions Migraine at Baseline and Week 12
279; 258; 3; 7; 1; 1
SECONDARY
Placebo-controlled Period: Migraine Specific HCRU - Total Number of Participants With Overnight Hospital Stays Due to Migraine at Baseline and Week 12
282; 264; 1; 1; 0; 1
SECONDARY
Open-label Period: Migraine Specific HCRU - Visits to a Family Doctor/General Practitioner at Week 24
239; 239; 26; 20; 11; 13
SECONDARY
Open-label Period: Migraine Specific HCRU - Visits to a Specialist at Week 24
239; 240; 29; 20; 7; 8
SECONDARY
Open-label Period: Migraine Specific HCRU - Number of Participants With Emergency Department Visits Due to Migraine at Week 24
277; 265; 3; 5; 0; 3
SECONDARY
Open-label Period: Migraine Specific HCRU - Number of Participants With Hospital Admissions Due to Migraine at Week 24
281; 271; 0; 2; 0; 2
SECONDARY
Open-label Period: Migraine Specific HCRU - Number of Participants With Overnight Hospital Stays Due to Migraine at Week 24
281; 270; 0; 3; 0; 1

Summary

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.

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05452239). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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