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

Sponsor

H. Lundbeck A/S (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05452239

Collaborator

(none)

570

Enrollment

Locations

Arms

Anticipated Duration (Months)

142.5

Patients Per Site

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Migraine Medication Overuse Headache	Drug: Eptinezumab Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

570 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

May 30, 2024

Anticipated Study Completion Date :

May 30, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Number of Monthly Migraine Days (MMDs) [Baseline to Weeks 1-4]

Secondary Outcome Measures

Change From Baseline in MMDs [Weeks 1-12 and Weeks 13-24]
Change From Baseline in the Number of Monthly Headache Days (MHDs) [Weeks 1-4, Weeks 1-12, and Weeks 13-24]
Change From Baseline in Average Daily Pain Assessment Score [Weeks 1-2, Weeks 13-24]
Change From Baseline in Monthly Days with Acute Medication Use [Weeks 1-4, Weeks 1-12, and Weeks 13-24]
Percentage of Participants Not Fulfilling the International Classification of Headache Disorders (ICHD-3) Diagnostic Criteria for Chronic Migraine (CM) [Weeks 1-4, Weeks 1-12, and Weeks 13-24]
Percentage of Participants Not Fulfilling the ICHD-3 Diagnostic Criteria for MOH [Weeks 1-4, Weeks 1-12, and Weeks 13-24]
Change From Baseline in MMDs with Acute Medication Use [Weeks 1-12 and Weeks 13-24]
Change from Baseline in Monthly Days of Medication Use (triptans, ergotamine, non-opioids, opioids, and combination analgesics) [Weeks 1-12 and Weeks 13-24]
Percentage of Participants with Migraine on the Day After Dosing [On the day after dosing]
Response: ≥50% Reduction From Baseline in MMDs [Baseline to Weeks 1-4 and Weeks 1-12]
Response: ≥75% Reduction From Baseline in MMDs [Baseline to Weeks 1-4 and Weeks 1-12]
Response: ≥50% Reduction From Baseline in MHDs [Baseline to Weeks 1-4 and Weeks 1-12]
Response: ≥75% Reduction From Baseline in MHDs [Baseline to Weeks 1-4 and Weeks 1-12]
Change from Baseline in Rate of Migraines and Headaches with Severe Pain Intensity [Weeks 1-4 and Weeks 1-12]
Patient Global Impression of Change (PGIC) Score [Week 4, Week 12, and Week 24]
The PGIC is a patient-reported measure of improvement in pain sensation and quality of life scored on a scale from 1 (very much improved) to 7 (very much worse).
Change in Most Bothersome Symptom (MBS) Score [Weeks 1-12 and Weeks 13-24]
Participants will identify a migraine-related symptom that is most bothersome for them. Participants will be asked to rate the improvement in this symptom from screening on a 7-point scale. The pre-specified bothersome items are: nausea, vomiting, sensitivity to light, sensitivity to sound.
Change From Baseline in the Headache Impact Test (HIT-6) Total Score [Week 4, Week 12, and Week 24]
The HIT-6 (v1.0) is a 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 is 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 is the sum of each response score and ranges from 36 to 78. The life impact derived from the total score is described as followed: Severe (≥60), Substantial (56 59), Some (50-55), Little to None (≤49).
Change From Baseline in the Migraine Disability Assessment (mMIDAS) Total Score [Baseline to Week 4, Week 12, and Week 24]
The mMIDAS is a self-reporting questionnaire designed to assess absenteeism (complete disability) and presenteeism (reduced participation) in several domains, including work, school, family, social, and leisure activities. The total number of days with disability is rated on a 4-point scale, from the lower total score that indicates a Little or No Disability; Mild Disability; Moderate Disability to the higher total score that indicates a Severe Disability.
Change From Baseline in the Migraine-Specific Quality of Life (MSQ v2.1) Sub-Scores [Baseline to Week 4, Week 12, and Week 24]
The MSQ v2.1 is 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 is scored on a 6-point scale ranging from 1 (none of the time) to 6 (all of the time). Raw domain scores are summed and transformed to a 0-to-100-point scale. Higher scores indicate better quality of life. Sub-scores: Role Function-Restrictive, Role Function-Preventive, Emotional Function)
Change From Baseline in the Health-Related Quality of Life (EQ-5D-5L) Visual Analogue Scale (VAS) Score [Baseline to Week 4, Week 12, and Week 24]
The EQ-5D-5L42 is a patient-reported assessment designed to measure the participant's wellbeing. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a VAS of the overall health state. Each descriptive item is rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems) and a single summary index (from 0 to 1) can be calculated. The VAS ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Change From Baseline in Health Care Resources Utilisation (HCRU) Score [Baseline to Week 12 and Week 24]
Migraine-specific health care resource utilization information will be collected in terms of outpatient health care professional visits, emergency room visits, hospital admissions, as well as duration of hospital stays.
Change From Baseline in Work Productivity as Measured Using the Work Productivity and Activity Impairment Questionnaire (WPAI) Sub-Scores [Baseline to Week 12 and Week 24]
The WPAI is designed to provide a quantitative measure of the work productivity and activity impairment due to a specific health problem (WPAI:M). The WPAI:M assesses activities over the preceding 7 days and consists of 6 items: 1 item assess employment status, 3 items assess the number of hours worked, the number of hours missed from work due to the participant's condition, or due to other reasons, and 2 visual numerical scales to assess how much the participant's condition affects their productivity at work and their ability to complete normal daily activities. Sub-scores: (Absenteeism, Presenteeism, Work productivity loss, Activity impairment)
Change From Baseline in Hospital Anxiety and Depression (HADS) Sub-Scores [Baseline to Week 12 and Week 24]
The HADS is a patient-rated scale designed to screen for anxiety and depressive states in non-psychiatric participants. The HADS consists of two sub-scales: the D-scale measures depression and the A-scale measures anxiety. Each sub-scale contains 7 items, and each item is rated from 0 (absent) to 3 (maximum severity). The score of each sub-scale ranges from 0 to 21 and are analysed separately.
Change From Baseline in Treatment Satisfaction Questionnaire for Medicine (9 Items) (TSQM-9) Score [Baseline to Week 4, Week 12, and Week 24]
The TSQM-9 is a generic questionnaire assessing the participants satisfaction with the medication. The tool consists of 9 items addressing effectiveness, side effects, convenience, and overall satisfaction of the study drug.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research of Central Florida - ClinEdge - PPDS	Winter Haven	Florida	United States	33880-3053
2	Legacy Clinical Solutions: Tandem Clinical Research, LLC - Clinedge - Louisiana - PPDS	Marrero	Louisiana	United States	70072-3151
3	Clinvest	Springfield	Missouri	United States	65810
4	Texas Center for Drug Development, Inc	Houston	Texas	United States	77081