A 1-year Trial to Inform About Long-term Exposure to Eptinezumab in Participants With Chronic Cluster Headache (cCH) (CHRONICLE)

Interventional, Open-label, Fixed-dose Multiple Administration Study to Evaluate Long-term Treatment With Eptinezumab in Patients With Chronic Cluster Headache

The main goal of this trial is to inform about long-term safety and tolerability of eptinezumab in participants with chronic cluster headache.

Study Overview

• Status: Completed
• Conditions: Chronic Cluster Headache
• Intervention / Treatment: Drug: Eptinezumab

Detailed Description

The participants who take part in this trial will be asked to stay in the trial for about a year. The participants will be asked to visit the trial site 7 times during the trial. In between trial site visits, they will have scheduled phone calls with the trial site staff. They will also be asked to keep track of their cluster headaches at home with a headache diary.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Hovedstaden
    • Glostrup, Hovedstaden, Denmark, 2600
      • Rigshospitalet Glostrup
  • Midtjylland
    • Viborg, Midtjylland, Denmark, 8800
      • Hospitalsenhed Midt og Regionshospitalet Viborg
• Finland
  • Southern Finland
    • Helsinki, Southern Finland, Finland, 00180
      • Terveystalo Ruoholahti
  • Western Finland
    • Turku, Western Finland, Finland, 20100
      • Terveystalo Turku Pulssi
• France
  • Côte-d'Or
    • Nice Cedex 1, Côte-d'Or, France, 91179 - 06003
      • Hôpital Cimiez
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Roger Salengro
  • Provence Alpes Cote d'Azur
    • Marseille Cedex 5, Provence Alpes Cote d'Azur, France, 13005
      • Hopital de La Timone
  • Rhône
    • Bron, Rhône, France, 69677
      • Hopital Pierre Wertheimer
    • Saint-Priest-en-Jarez, Rhône, France, 42055
      • Centre Hospitalier Universitaire de Saint-Etienne
  • Île-de-France
    • Paris, Île-de-France, France, 75010
      • Hopital Lariboisiere
• Germany
  • Berlin, Germany, 10117
    • Charite Campus Mitte
  • Hessen
    • Frankfurt/ Main, Hessen, Germany, 65929
      • Kopfschmerzzentrum Frankfurt
• Italy
  • Bologna, Italy, 40123
    • IRCCS Istituto delle Scienze Neurologiche di Bologna
  • Pavia, Italy, 27100
    • Fondazione Mondino - Istituto Neurologico Nazionale a Carattere Scientifico IRCCS
  • Turin, Italy, 10126
    • Ospedale Molinette - Clinica Neurologica II - Centro Cefalee
  • Milan
    • Milano, Milan, Italy, 20133
      • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Fondazione Istituto Neurologico Car...
  • Roma
    • Rome, Roma, Italy, 00163
      • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - San Raffaele Pisana
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6532 SZ
      • Canisius-Wilhelmina Ziekenhuis
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 GN
      • Brain Research Center - Amsterdam
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío
  • Valladolid, Spain, 47010
    • Hospital Clinico Universitario de Valladolid
  • València, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• United Kingdom
  • England
    • Liverpool, England, United Kingdom, L9 7LJ
      • The Walton Centre NHS Foundation Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
• United States
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Neurology and Headache
  • Michigan
    • Ann Arbor, Michigan, United States, 48104-5131
      • Michigan Headache and Neurological Institute
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute - Amherst
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Neurological Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital - Center City Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant has a diagnosis of cCH as defined by International Headache Society (IHS) International Classification of Headache Disorders third edition (ICHD-3) classification with a history of cCH of at least 12 months prior to the Screening Visit.
• The participant has a medical history of onset of cluster headache at ≤50 years of age.
• The participant has an adequately documented record of previous abortive, transitional and preventive medication use for cCH, for at least 12 months prior to the Screening Visit.
• The participant is able to distinguish cluster headache attacks from other headaches (such as tension-type headaches, migraine).

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 chronic tension-type headache, 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 neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or longer than 1 hour).
• Participants with a lifetime history of psychosis, bipolar mania, or dementia. 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.
• The participant has attempted suicide or is, at Screening Visit, at significant risk of suicide.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eptinezumab; Participants will receive 4 intravenous (IV) infusions with eptinezumab at Baseline (Day 0) and at the end of Weeks 12, 24, and 36.	Drug: Eptinezumab; Eptinezumab will be administered per schedule specified in the arm description.; Other Names: Vyepti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (AEs)	A treatment-emergent AE was defined as any on-treatment untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	From the day of first dose of study drug (Baseline [Week 0]) up to Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion From Chronic Cluster Headache (cCH) to Episodic Cluster Headache (eCH): Number of Participants With No Cluster Headache (CH) Attacks for ≥3 Consecutive Months (≥12 Consecutive Weeks)	Participants counted as converting from cCH to eCH if they had no CH attacks for at least 3 months.	Week 1 to Week 48
Change From Baseline in Weekly Number of Times an Abortive Therapy (Oxygen and/or Triptans) Was Used	Abortive therapy was defined as oxygen and/or triptans, where it counted as 2 times if oxygen and triptans were used for the same attack.	Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Change From Baseline in Weekly Number of Times An Abortive Therapy (Oxygen) Was Used		Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Change From Baseline in Weekly Number of Times An Abortive Therapy (Triptans) Were Used		Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Change From Baseline in the Average Number of Weekly Attacks	The participant completed a CH eDiary, daily, and record for each day/week whether he/she had any CH attacks.	Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Change From Baseline in the Number of Weekly Attacks	The average of the estimated change from baseline in the number of weekly attacks across the first 4 weeks after the infusion is shown.	Baseline (Week 0), Weeks 1-4
Change From Baseline in the Number of Weekly Attacks	The average of the estimated change from baseline in the number of weekly attacks across the first 2 weeks after the infusion is shown.	Baseline (Week 0), Weeks 1-2
Change From Baseline in the Number of Monthly Attacks	The average of the estimated change from baseline in the number of monthly attacks across the first 12 months after the infusion is shown.	Baseline (Week 0), Months 1-12
Change From Baseline in the Average Attack Related Daily Pain (Including Days With no Attacks), as Assessed Using the 5-point Self-rating Pain Severity Scale	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).	Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Response: Number of Participants With ≥30% Reduction From Baseline in Number of Weekly Attacks		Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Response: Number of Participants With ≥50% Reduction From Baseline in Number of Weekly Attacks		Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
Response: Number of Participants With ≥75% Reduction From Baseline in Number of Weekly Attacks		Baseline (Week 0), Weeks 1, 2, 3, 4, 13, 14, 15, 16, 25, 26, 27, 28, 37, 38, 39, 40
cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (>=4 Consecutive Weeks)	Participants counted as being in remission if they had no cluster headache attacks for at least 1 month.	Week 1 to Week 48
cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (>=4 Consecutive Weeks Between the First and Second Infusion)		Week 1 to Week 12
cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (>=4 Consecutive Weeks Between the Second and Third Infusion)		Week 13 to Week 24
cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (>=4 Consecutive Weeks Between the Third and Fourth Infusion)		Week 25 to Week 36
cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (>=4 Consecutive Weeks Within the First 12 Weeks After the Fourth Infusion)		Week 37 to Week 48
Number of Participants Who Received a Transitional Therapy During the Treatment Period	Transitional treatments were defined as greater occipital nerve (GON) block or oral steroids.	Week 1 to Week 48
Patient Global Impression of Change (PGIC) Score	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.	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Change From Baseline in Sleep Impact Scale (SIS) Domain Scores Over the Time	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.	Baseline (Week 0), Weeks 4, 12, 16, 24, 28, 36, 40, 48
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Score at Weeks 4, 16, 28, 40 and 48	The EQ-5D-5L is a patient-reported assessment designed to measure the participant's well-being. It consists of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety). Each descriptive item is rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems).	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Change From Baseline in the EQ-5D-5L Visual Analog Scale (VAS) Score at Weeks 4, 16, 28, 40 and 48	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).	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Change From Baseline in the Work Productivity Activity Impairment: General Health Second Version (WPAI:GH2.0) Sub-Scores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Weeks 4, 16, 28, 40 and 48	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.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Health Care Resource Utilization - Number of Visits to a Family Doctor/General Practitioner	Number of participants who visited a family doctor/general practitioner has been reported.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Health Care Resource Utilization - Number of Visits to a Specialist	Number of participants who visited a specialist has been reported.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Health Care Resource Utilization - Number of Emergency Department Visits Due to Cluster Headache	Number of participants who visited an emergency department due to CH has been reported.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Health Care Resource Utilization - Number of Hospital Admissions Due to Cluster Headache	Number of participants admitted to the hospital due to CH has been reported.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48
Health Care Resource Utilization - Total Number of Overnight Hospital Stays Due to Cluster Headache	Number of participants who had overnight hospital stays due to CH has been reported.	Baseline (Week 0), Weeks 4, 16, 28, 40, 48

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Investigators: Study Director: Email contact via H. Lundbeck A/S, H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache
• Other Study ID Numbers: 19385A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No