Eptinezumab in Participants With Episodic Cluster Headache (ALLEVIATE)

• ClinicalTrials.gov Identifier: NCT04688775
• Recruitment Status: Completed
• First Posted: December 30, 2020
• Last Update Posted: November 7, 2023
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Tracking Information

• First Submitted Date: December 24, 2020
• First Posted Date: December 30, 2020
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: December 23, 2020
• Actual Primary Completion Date: June 14, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2022): Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-2 [ Time Frame: Baseline, Weeks 1-2 ]
• Original Primary Outcome Measures (submitted: December 24, 2020): Change from baseline in number of weekly attacks (Weeks 1-2) [ Time Frame: Weeks 1-2 ]

Current Secondary Outcome Measures (submitted: November 14, 2022)

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

Original Secondary Outcome Measures (submitted: December 24, 2020)

• Response: >= 50% reduction in number of weekly attacks (Weeks 1-2) [ Time Frame: Weeks 1-2 ]
• Change from baseline in weekly number of times an abortive therapy was used (Weeks 1-2) [ Time Frame: Weeks 1-2 ]
• Change from baseline in the number of daily attacks (Days 1-3) [ Time Frame: Days 1-3 ]
• Change from baseline in weekly number of days with less than 3 attacks per day (Weeks 1-2) [ Time Frame: Weeks 1-2 ]
• Time to resolution of cluster headache bout within 4 weeks after the first Investigational Medicinal Product (IMP) infusion [ Time Frame: From baseline to Week 4 ]
• Number of attacks starting within 24 hours of the start of the first infusion [ Time Frame: From first infusion to 24-hours post dose ]
• Change from baseline in the daily mean score on 5-point self-rating pain severity scale (Days 1-3) [ Time Frame: Days 1-3 ]
• Change from baseline to Week 1 in number of attacks [ Time Frame: From baseline to Week 1 ]
• Change from baseline to Week 2 in number of attacks [ Time Frame: From baseline to Week 2 ]
• Response: >= 50% reduction in number of attacks in Week 1 [ Time Frame: Week 1 ]
• Response: >= 30% reduction in number of attacks in Week 1 [ Time Frame: Week 1 ]
• Response: >= 30% reduction in number of weekly attacks (Weeks 1-2) [ Time Frame: Weeks 1-2 ]
• Change from baseline in weekly integrated measure of frequency and intensity of pain (Weeks 1-2) [ Time Frame: 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
• Change from baseline to Week 1 in integrated measure of frequency and intensity of pain [ Time Frame: Week 1 ]
  For Week 1 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week
• Change from baseline to Week 2 in weekly integrated measure of frequency and intensity of pain [ Time Frame: Week 2 ]
  For Week 2 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week
• Change from baseline in the number of weekly attacks (Weeks 1-4) [ Time Frame: Weeks 1-4 ]
• Change from baseline in weekly integrated measure of frequency and intensity of pain (Weeks 1-4) [ Time Frame: 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
• 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 [ Time Frame: Weeks 1, 2, 3 and 4 ]
• Change from baseline in number of attacks for Week 1, 2, 3 and 4 [ Time Frame: Weeks 1, 2, 3 and 4 ]
• Patient Global Impression of Change (PGIC) score at Week 1, 2 and 4 [ Time Frame: Weeks 1, 2 and 4 ]
• Change from baseline in Sleep Impact Scale (SIS) score at Weeks 2 and 4 [ Time Frame: Weeks 2 and 4 ]
• Change from baseline in Euroqol 5 Dimension 5-Levels (EQ-5D-5L) at Week 2 and 4 [ Time Frame: Weeks 2 and 4 ]
• Change from baseline in Health Care Resource Utilization (HCRU) at Week 4 [ Time Frame: Week 4 ]
• Change from baseline in the Work Productivity Activity Impairment Questionnaire at Week 4 [ Time Frame: Week 4 ]
  General Health second version (WPAI:GH2.0) subscores (Absenteeism, Presenteeism, Work productivity loss, Activity impairment)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Eptinezumab in Participants With Episodic Cluster Headache
• Official Title: 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
• Brief Summary: The purpose of this study is to evaluate the efficacy of eptinezumab in participants with episodic Cluster Headache (eCH)

Detailed Description

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Cluster Headache, Episodic

Intervention

• Drug: Eptinezumab
  Eptinezumab - concentrate for solution for infusion, intravenously
• Drug: Placebo
  Placebo - 100 milliliters (mL) of 0.9% normal saline, intravenously

Study Arms

• Experimental: Sequence 1: Eptinezumab Then Placebo
  Eptinezumab in the Placebo-controlled Period, followed by administration of placebo in the Active Treatment Period
  Interventions:

  • Drug: Eptinezumab
  • Drug: Placebo
• Experimental: Sequence 2: Placebo Then Eptinezumab
  Placebo in the Placebo-controlled Period, followed by administration of eptinezumab in the Active Treatment Period
  Interventions:

  • Drug: Eptinezumab
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 18, 2023): 232
• Original Estimated Enrollment (submitted: December 24, 2020): 304
• Actual Study Completion Date: October 5, 2023
• Actual Primary Completion Date: June 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Italy, Japan, Netherlands, Norway, Portugal, Russian Federation, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04688775
• Other Study ID Numbers: 19386A
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lundbeck A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lundbeck A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@Lundbeck.com

• PRS Account: H. Lundbeck A/S
• Verification Date: November 2023