Eptinezumab in Participants With Episodic Cluster Headache

H. Lundbeck A/S231 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

231

Conditions

Cluster Headache, Episodic

Interventions

EptinezumabDRUG

Eptinezumab - concentrate for solution for infusion, intravenously

PlaceboDRUG

Placebo - 100 milliliters (mL) of 0.9% normal saline, intravenously

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (120)

Outcomes

Primary Outcomes

Change From Baseline in the Number of Weekly Cluster Headache (CH) Attacks, Averaged Over Weeks 1-2

The participant completed a CH eDiary, daily, and recorded for each day/week whether he/she had any CH attacks. For each CH attack, the start date and time was collected. The participant recorded further daily information regarding CH characteristics and intake of acute medication for CH. CH items were assessed with a yes/no response.

Time frame: Baseline (Week 0), Weeks 1-2

Secondary Outcomes

Number of Participants With ≥50% Reduction From Baseline in Number of Weekly Attacks Over Weeks 1-2

Time frame: Baseline (Week 0), Weeks 1-2

Change From Baseline in the Number of Weekly Times an Abortive Medication Was Used, Averaged Over Weeks 1-2

Abortive medications included the use of triptans or oxygen (O2).

Time frame: Baseline (Week 0), Weeks 1-2

Change From Baseline in the Number of Daily Attacks, Averaged Over Days 1-3

Time frame: Baseline (Week 0), Days 1-3

Change From Baseline in the Number of Days With <3 Attacks Per Day, Averaged Over Weeks 1-2

Time frame: Baseline (Week 0), Weeks 1-2

Time From First Infusion of IMP to Resolution of Cluster Headache Bout Within the First 4 Weeks

Presented here is the result of the analysis of time from first infusion of IMP to resolution of cluster headache bout. The hazard ratio estimate is an estimate from the Cox model of time to resolution.

Time frame: From first infusion (Baseline, Day 0) to 4 weeks

Change From Baseline in Number of Attacks Starting ≤24 Hours After the Start of the First Infusion of IMP

Data from ClinicalTrials.gov

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Barrow Neurological Institute

Phoenix, Arizona, United States

Mayo Clinic in Arizona - Phoenix Campus

Phoenix, Arizona, United States

Keck School of Medicine of USC

Los Angeles, California, United States

Clinical Research Institute

Los Angeles, California, United States

Stanford Neurosciences Health Center

Palo Alto, California, United States

Neurology Colorado - Denver Advanced Neurological Evaluation and Treatment Center

Denver, Colorado, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

New England Institute for Neurology and Headache

Stamford, Connecticut, United States

Accel Research Sites - Tampa

Tampa, Florida, United States

Diamond Headache Clinic

Chicago, Illinois, United States

...and 110 more locations

Time frame: From first infusion in the placebo-controlled period (Baseline, Day 0) to 24-hours after the first infusion in the placebo-controlled period

Change From Baseline in the Daily Mean Score on 5-Point Self-Rating Pain Severity Scale, Averaged Over Days 1-3

The severity of pain was rated on an ordinal scale that ranged from 0 to 4 with higher scores indicating more headache pain (headache pain ratings: 0 = none/barely any pain; 1 = mild; 2 = moderate; 3 = severe; 4 = excruciating).

Time frame: Baseline (Week 0), Days 1-3

Change From Baseline to Week 1 in the Number of Weekly Attacks

Time frame: Baseline (Week 0), Week 1

Change From Baseline to Week 2 in the Number of Weekly Attacks

Time frame: Baseline (Week 0), Week 2

Number of Participants With ≥50% Reduction From Baseline in Number of Weekly Attacks in Week 1

Time frame: Baseline (Week 0), Week 1

Number of Participants With ≥30% Reduction From Baseline in Number of Weekly Attacks in Week 1

Time frame: Baseline (Week 0), Week 1

Number of Participants With ≥30% Reduction From Baseline in Number of Weekly Attacks Over Weeks 1-2

Time frame: Baseline (Week 0), Weeks 1-2

Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of Pain, Averaged Over Weeks 1-2

The weekly integrated measure of frequency and intensity of pain calculates a singular numerical value for frequency and intensity of pain by adding the intensity rating (Worst pain on a 5-point Self-rating pain severity scale) for each attack during that week. The intensity of pain for each attack was rated on an ordinal scale that ranged from 0 to 4 with higher scores indicating more headache pain (0 = none/barely any pain; 1 = mild; 2 = moderate; 3 = severe; 4 = excruciating). The total weekly score could range from 0 (no attacks and/or no pain) to no specified upper limit, with lower scores representing better outcomes.

Time frame: Baseline (Week 0), Weeks 1-2

Change From Baseline to Week 1 in Weekly Integrated Measure of Frequency and Intensity of Pain

Time frame: Baseline (Week 0), Week 1

Change From Baseline to Week 2 in Weekly Integrated Measure of Frequency and Intensity of Pain

Time frame: Baseline (Week 0), Week 2

Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-4

Time frame: Baseline (Week 0), Weeks 1-4

Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of Pain, Averaged Over Weeks 1-4

The weekly integrated measure of frequency and intensity of pain score calculates a singular numerical value for frequency and intensity of pain by adding the intensity rating (Worst pain on a 5-point Self-rating pain severity scale) for each attack during that week. The intensity of pain for each attack was rated on an ordinal scale that ranged from 0 to 4 with higher scores indicating more headache pain (0 = none/barely any pain; 1 = mild; 2 = moderate; 3 = severe; 4 = excruciating). The total weekly score could range from 0 (no attacks and/or no pain) to no specified upper limit, with lower scores representing better outcomes.

Time frame: Baseline (Week 0), Weeks 1-4

Change From Baseline in the Mean Score on 5-Point Self-Rating Pain Severity Scale (Average Per Attack Over a Week) for Weeks 1, 2, 3, and 4

The severity of pain for each attack was rated on an ordinal scale that ranged from 0 to 4 with higher scores indicating more headache pain (headache pain ratings: 0 = none/barely any pain; 1 = mild; 2 = moderate; 3 = severe; 4 = excruciating).

Time frame: Baseline (Week 0), Weeks 1, 2, 3, and 4

Change From Baseline in the Number of Weekly Attacks for Each of Weeks 3 and 4

Time frame: Baseline (Week 0), Weeks 3-4

Patient Global Impression of Change (PGIC) Score at Weeks 1, 2, and 4

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). Lower scores indicate better health status.

Time frame: Weeks 1, 2, and 4

Change From Baseline in Sleep Impact Scale (SIS) Domain Scores at Weeks 2 and 4

The SIS is a patient-reported clinical outcome assessment used to assess quality of life resulting from sleep disturbance. The SIS questionnaire includes 35 items belonging to 7 domains to assess sleep impact on: daily activities; emotional well-being; emotional impact; energy/fatigue; social well-being; mental fatigue; and satisfaction with sleep. Each item, for 6 out of the 7 domains, is rated on a 5-point scale ranging from 1 (always or all of the time) to 5 (never or none of the time), whereas satisfaction with sleep is rated on a 5-point scale ranging from 1 (very satisfied) to 5 (very dissatisfied). Each domain yields a score ranging from 0 to 100, which is presented here. A higher score for Daily Activities, Emotional Well-being, Emotional Impact, Energy/Fatigue, Social Well-being, and Mental Fatigue indicates better quality of life. A lower score for Satisfaction with Sleep indicates a higher quality of life.

Time frame: Baseline (Week 0), 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

The EQ-5D-5L VAS is a participant-reported assessment designed to measure the participant's well-being and ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).

Time frame: Baseline (Week 0), Weeks 2 and 4

Health Care Resource Utilization (HCRU) Score: Number of Visits to a Family Doctor/General Practitioner

Number of participants who visited a family doctor/general practitioner has been reported.

Time frame: Week 4

HCRU Score: Number of Visits to a Specialist

Number of participants who visited a specialist has been reported.

Time frame: Week 4

HCRU Score: Number of Emergency Department Visits Due to Cluster Headache

Number of participants who visited an emergency department due to CH was reported.

Time frame: Week 4

HCRU Score: Number of Hospital Admissions Due to Cluster Headache

Number of participants who were admitted to a hospital due to CH was reported.

Time frame: Week 4

HCRU Score: Number of Overnight Hospital Stays Due to Cluster Headache

Number of participants who stayed overnight in a hospital due to CH was reported.

Time frame: Week 4

Change From Baseline in the Work Productivity Activity Impairment (WPAI) Questionnaire Subscores at Week 4

The WPAI:GH2.0 is a patient self-rated clinical outcome assessment designed to provide a quantitative measure of the work productivity and activity impairment due to a health condition. The WPAI:GH2.0 assesses activities over the preceding 7 days and consists of 6 items: 1 item assesses employment (yes/no); 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 assess how much the participant's condition affects his/her productivity at work and his/her ability to complete normal daily activities. Each item (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) was calculated into an impairment percentage ranging from 0 to 100%, with higher numbers indicating greater impairment and less productivity (i.e. worse outcomes). Change from baseline for each item is shown here.

Time frame: Baseline (Week 0), Week 4