Eptinezumab in Participants With Episodic Cluster Headache

Cluster Headache, Episodic Clinical Trial

— ALLEVIATE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04688775
• Other study ID #: 19386A
• Status: Completed
• Phase: Phase 3
• Start date: December 23, 2020
• Est. completion date: October 5, 2023

Study information

• Verified date: November 2023
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: October 5, 2023
• Est. primary completion date: June 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cluster Headache
• Cluster Headache, Episodic
• Headache

Intervention

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

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge	West-Vlaanderen
Belgium	Universitair Ziekenhuis Brussel	Brussels	Bruxelles-Capitale
Belgium	Centre Hospitalier Chretien - Clinique MontLégia	Liège
Czechia	Mestska Nemocnice Ostrava	Ostrava	Moravian-Silesian
Czechia	Fakultní Thomayerova nemocnice	Praha 4	Prague
Czechia	FORBELI s.r.o. Neurologicka Ambulance	Praha 6	Prague
Czechia	Institut Neuropsychiatrické Péce	Praha 8	Prague
Denmark	Aarhus Universitetshospital	Aarhus N	Midtjylland
Denmark	Sydvestjysk Sygehus - Esbjerg	Esbjerg
Denmark	Rigshospitalet Glostrup	Glostrup	Hovedstaden
Denmark	Hospitalsenhed Midt og Regionshospitalet Viborg	Viborg	Midtjylland
Estonia	Ida-Viru Keskhaigla	Kohtla-Järve	Ida-Virumaa
Estonia	Confido Meditsiinikeskus	Tallinn	Harjumaa
Estonia	Tartu Ülikooli Kliinikum	Tartu	Tartumaa
Finland	Terveystalo Ruoholahti	Helsinki	Southern Finland
Finland	Tampereen Yliopistollinen Sairaala (TAYS)	Tampere	Länsi-Suomen Lääni
Finland	Terveystalo Tampere	Tampere
Finland	Terveystalo Turku Pulssi	Turku	Western Finland
France	Hôpital Pierre Wertheimer	Bron
France	Centre Hospitalier Universitaire de Clermont-Ferrand	Clermont-Ferrand Cedex 1	Auvergne-Rhône-Alpes
France	Hôpital Roger Salengro	Lille	Nord
France	Hôpital de la Timone	Marseille Cedex 5	Provence Alpes Cote d'Azur
France	Centre Hospitalier Annecy Genevois	Metz-Tessy	Rhone-Alpes
France	Hôpital Cimiez	Nice Cedex 1	Côte-d'Or
France	Hôpital Lariboisière	Paris	Île-de-France
France	Centre Hospitalier Universitaire de Saint-Étienne	Saint-Priest-en-Jarez	Rhône
Georgia	Archangel Saint Michael Multiprofile Clinical Hospital	Tbilisi
Georgia	Aversi Clinic - Central Branch	Tbilisi
Georgia	Consilium Medulla Multiprofile Clinic	Tbilisi
Georgia	Pineo Medical Ecosystem	Tbilisi
Georgia	Simon Khechinashvili University Hospital	Tbilisi
Germany	Charité Campus Mitte	Berlin
Germany	Neurologische Praxis Dr. Stude	Bochum	Nordrhein-Westfalen
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	Praxis für Neurologie, Psychosomatik, Nervenheilkunde, Psychotherapie und Spezielle Schmerztherapie	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Kopfschmerzzentrum Frankfurt	Frankfurt/ Main	Hessen
Germany	Universität Heidelberg	Heidelberg	Baden-Württemberg
Germany	Schmerzklinik Kiel	Kiel	Schleswig-Holstein
Germany	LMU Klinikum - Campus Grosshadern	München	Bayern
Germany	Universitätsmedizin Rostock	Rostock	Mecklenburg-Western-Pommerania
Greece	Eginition University - General Hospital of Athens	Athens	Attica
Greece	401 General Military Hospital of Athens	Athina	Attica
Greece	Mediterraneo Hospital	Glyfada	Attica
Greece	University General Hospital of Larissa	Larissa	Thessaly
Greece	General Hospital of Patras Agios Andreas	Patra	Western Greece
Greece	Euromedica General Clinic - Thessaloniki	Thessaloniki
Italy	Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari	Bari
Italy	IRCCS Istituto Delle Scienze Neurologiche di Bologna	Bologna
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze	Florence
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Fondazione Istituto Neurologico Car...	Milano
Italy	Azienda Ospedaliero - Universitaria di Modena	Modena
Italy	Azienda Ospedaliera Universitaria - Universita degli Studi della Campania Luigi Vanvitelli	Napoli
Italy	Fondazione Mondino - Istituto Neurologico Nazionale a Carattere Scientifico IRCCS	Pavia
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - San Raffaele Pisana	Rome	Roma
Italy	Universita Campus Bio-Medico di Roma	Rome
Italy	Ospedale Molinette - Clinica Neurologica II - Centro Cefalee	Turin
Japan	Saitama Neuropsychiatric Institute	Saitama-shi	Saitama
Japan	Sendai Headache And Neurology Clinic	Sendai-shi	Miyagi
Japan	Japanese Red Cross Shizuoka Hospital	Shizuoka-shi	Shizuoka
Netherlands	Brain Research Center - Amsterdam	Amsterdam	Noord-Holland
Netherlands	Zuyderland Medisch Centrum Sittard-Geleen	Geleen	Limburg
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen	Gelderland
Norway	Oslo Hodepinesenter	Oslo
Norway	St. Olavs Hospital - Universitetssykehuset I Trondheim	Trondheim
Portugal	Hospital Garcia de Orta	Almada	Setúbal
Portugal	Hospital Prof. Doutor Fernando Fonseca	Amadora	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Centro Hospitalar Universitario Lisboa Norte, E.P.E - Hospital De Santa Maria	Lisbon	Lisboa
Russian Federation	Kazan State Medical University	Kazan	Tartarstan
Russian Federation	First Moscow State Medical University named after I.M. Sechenov	Moscow
Russian Federation	University Headache Clinic	Moscow
Russian Federation	City Hospital No. 33 of the Leninsky District of the city of Nizhny Novgorod	Nizhnij Novgorod	Nizhegorodskaya Oblast
Russian Federation	LLC Scientific and Practical Medical Center Innovation and Health	Novosibirsk
Russian Federation	Perm State Medical University named after E. A. Wagner of the Ministry of Healthcare of the Russi...	Perm	Permsky
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen Macarena	Castilleja de la Cuesta	Sevilla
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Spain	Hospital Clínico Universitario de Valencia	València
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Sweden	Hallands sjukhus Halmstad	Halmstad	Hallands Län
Sweden	Karolinska Universitetssjukhuset Huddinge	Huddinge	Stockholms Län
Sweden	Centralsjukhuset Karlstad	Karlstad	Värmlands Län
Sweden	Skåneuro Privatmottagning	Lund	Skåne Län
Sweden	Danderyds Sjukhus	Stockholm	Stockholms Län
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull	England
United Kingdom	The Walton Centre NHS Foundation Trust	Liverpool	England
United Kingdom	King's College Hospital NHS Foundation Trust	London	England
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle-upon-Tyne	England
United Kingdom	Northern Care Alliance NHS Foundation Trust	Salford	England
United States	Dent Neurologic Institute - Amherst	Amherst	New York
United States	Michigan Headache and Neurological Institute	Ann Arbor	Michigan
United States	Diamond Headache Clinic	Chicago	Illinois
United States	Cleveland Clinic - Neurological Institute	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Neurology Colorado - Denver Advanced Neurological Evaluation and Treatment Center	Denver	Colorado
United States	Headache Wellness Center	Greensboro	North Carolina
United States	Mischer Neuroscience Institute	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Clinical Research Institute	Los Angeles	California
United States	Keck School of Medicine of USC	Los Angeles	California
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	New York University School of Medicine	New York	New York
United States	Hightower Clinical	Oklahoma City	Oklahoma
United States	Stanford Neurosciences Health Center	Palo Alto	California
United States	Thomas Jefferson University Hospital - Center City Campus	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Mayo Clinic in Arizona - Phoenix Campus	Phoenix	Arizona
United States	The Headache Center Mississippi	Ridgeland	Mississippi
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Clinvest Research	Springfield	Missouri
United States	New England Institute for Neurology and Headache	Stamford	Connecticut
United States	Accel Research Sites - Tampa	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Denmark,  Estonia,  Finland,  France,  Georgia,  Germany,  Greece,  Italy,  Japan,  Netherlands,  Norway,  Portugal,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-2		Baseline, Weeks 1-2
Secondary	Percentage of Participants With =50% Reduction From Baseline in Number of Weekly Attacks Over Weeks 1-2		Baseline, Weeks 1-2
Secondary	Change From Baseline in the Number of Weekly Times an Abortive Medication Was Used, Averaged Over Weeks 1-2		Baseline, Weeks 1-2
Secondary	Change From Baseline in the Number of Daily Attacks, Averaged Over Days 1-3		Baseline, Days 1-3
Secondary	Change From Baseline in the Number of Days With <3 Attacks Per Day, Averaged Over Weeks 1-2		Baseline, Weeks 1-2
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in the Number of Weekly Attacks to Week 1		Baseline, Week 1
Secondary	Change From Baseline in the Number of Weekly Attacks to Week 2		Baseline, Week 2
Secondary	Percentage of Participants With =50% Reduction From Baseline in Number of Attacks in Week 1		Baseline, Week 1
Secondary	Percentage of Participants With =30% Reduction From Baseline in Number of Attacks in Week 1		Baseline, Week 1
Secondary	Percentage of Participants With =30% Reduction in Number of Weekly Attacks Over Weeks 1-2		Baseline, Weeks 1-2
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in the Number of Weekly Attacks, Averaged Over Weeks 1-4		Baseline, Weeks 1-4
Secondary	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
Secondary	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
Secondary	Change From Baseline in Number of Attacks for Weeks 3-4		Baseline, Weeks 3-4
Secondary	Patient Global Impression of Change (PGIC) Score at Weeks 1, 2, and 4		Weeks 1, 2, and 4
Secondary	Change From Baseline in Sleep Impact Scale (SIS) Domain Scores at Weeks 2 and 4		Baseline, Weeks 2 and 4
Secondary	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
Secondary	Health Care Resource Utilization (HCRU) Score at Week 4		Week 4
Secondary	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