Eptinezumab in Participants With Episodic Cluster Headache

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of eptinezumab in participants with episodic Cluster Headache (eCH)

Detailed Description
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Eligible participants will be randomly assigned to receive treatment, in a blinded manner, two infusions of either eptinezumab or placebo in a cross-over manner during the Placebo-controlled Period and Active Treatment Period of the study. The total duration of the study after randomization is 24 weeks, including a safety follow-up period of 8 weeks.

Official Title
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Interventional, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Delayed-Start Study to Evaluate the Efficacy and Safety of Eptinezumab in Patients With Episodic Cluster Headache

Conditions
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Cluster Headache, Episodic

Intervention / Treatment
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* Drug: Eptinezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has episodic cluster headache, as defined by International Headache Society (IHS) International Classification of Headache Disorders 3rd Edition (ICHD-3) classification, with an adequately documented record or reliable history of eCH of at least 12 months prior to Screening Visit 1. The participant has a prior history of cluster period(s) lasting 6 weeks or longer, when untreated. The participant is able to distinguish cluster headache attacks from other headaches (that is; tension-type headaches, migraine). The participant is, at Screening Visit 2, in cluster headache bout, characterized by the presence of at least one typical cluster headache attack, that started not later than 1 week prior to Screening Visit 2. The participant has a medical history of first symptoms of cluster headache from ≤60 years of age. Exclusion Criteria The participant has experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway (anti-CGRP monoclonal antibodies [mAbs] and gepants). The participant has confounding and clinically significant pain syndromes (for example, fibromyalgia, complex regional pain syndrome). The participant has a history or diagnosis of hypnic headache, hemicrania continua, new daily persistent headache, chronic migraine 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). Participants with a lifetime history of psychosis, bipolar mania, or dementia are excluded. Participants with other psychiatric conditions whose symptoms are not controlled or who have not been adequately treated for a minimum of 6 months prior to Screening Visit 2 are also excluded. The participant is, at Screening Visit 2, at significant risk of suicide. The participant has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism). Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: Eptinezumab Then Placebo<br>Eptinezumab in the Placebo-controlled Period, followed by administration of placebo in the Active Treatment Period | Drug: Eptinezumab<br>* Eptinezumab - concentrate for solution for infusion, intravenously<br>Drug: Placebo<br>* Placebo - 100 milliliters (mL) of 0.9% normal saline, intravenously<br>|
| Experimental: Sequence 2: Placebo Then Eptinezumab<br>Placebo in the Placebo-controlled Period, followed by administration of eptinezumab in the Active Treatment Period | Drug: Eptinezumab<br>* Eptinezumab - concentrate for solution for infusion, intravenously<br>Drug: Placebo<br>* Placebo - 100 milliliters (mL) of 0.9% normal saline, intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-2 |  | Baseline, Weeks 1-2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥50% Reduction From Baseline in Number of Weekly Attacks Over Weeks 1-2 |  | Baseline, Weeks 1-2 | 
| Change From Baseline in the Number of Weekly Times an Abortive Medication Was Used, Averaged Over Weeks 1-2 |  | Baseline, Weeks 1-2 | 
| Change From Baseline in the Number of Daily Attacks, Averaged Over Days 1-3 |  | Baseline, Days 1-3 | 
| Change From Baseline in the Number of Days With <3 Attacks Per Day, Averaged Over Weeks 1-2 |  | Baseline, Weeks 1-2 | 
| Time From First Infusion of Investigation Medicinal Product (IMP) to Resolution of Cluster Headache Bout Within the First 4 Weeks |  | From Baseline to Week 4 | 
| Number of Attacks Starting ≤24 Hours After the Start of the First Infusion of IMP |  | From first infusion (Day 0) to 24-hours post infusion | 
| Change From Baseline in the Daily Mean Score on 5-Point Self-Rating Pain Severity Scale, Averaged Over Days 1-3 |  | Baseline, Days 1-3 | 
| Change From Baseline in the Number of Weekly Attacks to Week 1 |  | Baseline, Week 1 | 
| Change From Baseline in the Number of Weekly Attacks to Week 2 |  | Baseline, Week 2 | 
| Percentage of Participants With ≥50% Reduction From Baseline in Number of Attacks in Week 1 |  | Baseline, Week 1 | 
| Percentage of Participants With ≥30% Reduction From Baseline in Number of Attacks in Week 1 |  | Baseline, Week 1 | 
| Percentage of Participants With ≥30% Reduction in Number of Weekly Attacks Over Weeks 1-2 |  | Baseline, Weeks 1-2 | 
| Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of pain, Averaged Over Weeks 1-2 | For each week add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week. | Baseline, Weeks 1-2 | 
| Change From Baseline to Week 1 in Integrated Measure of Frequency and Intensity of Pain | For Week 1 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week. | Baseline, Week 1 | 
| Change From Baseline to Week 2 in Weekly Integrated Measure of Frequency and Intensity of Pain | For Week 2 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week. | Baseline, Week 2 | 
| Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-4 |  | Baseline, Weeks 1-4 | 
| Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of Pain (Weeks 1-4) | For each week add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week. | Baseline, Weeks 1-4 | 
| Change From Baseline in the Mean Score on 5-Point Self-Rating Pain Severity Scale (Average Per Week) for Weeks 1, 2, 3, and 4 |  | Baseline, Weeks 1, 2, 3, and 4 | 
| Change From Baseline in Number of Attacks for Weeks 3-4 |  | Baseline, Weeks 3-4 | 
| Patient Global Impression of Change (PGIC) Score at Weeks 1, 2, and 4 |  | Weeks 1, 2, and 4 | 
| Change From Baseline in Sleep Impact Scale (SIS) Domain Scores at Weeks 2 and 4 |  | Baseline, Weeks 2 and 4 | 
| Change From Baseline in Euroqol 5-Dimension 5-Levels (EQ-5D-5L) Visual Analogue Scale (VAS) at Weeks 2 and 4 |  | Baseline, Weeks 2 and 4 | 
| Health Care Resource Utilization (HCRU) Score at Week 4 |  | Week 4 | 
| Change From Baseline in the Work Productivity Activity Impairment (WPAI) Questionnaire Score at Week 4 | General Health second version (WPAI:GH2.0) sub-scores (Absenteeism, Presenteeism, Work productivity loss, Activity impairment) | Baseline, Week 4 |