ALLEVIATE: Eptinezumab in Participants With Episodic Cluster Headache

Sponsor

H. Lundbeck A/S (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04688775

Collaborator

(none)

304

Enrollment

111

Locations

Arms

30.3

Anticipated Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cluster Headache, Episodic	Drug: Eptinezumab Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

304 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 23, 2020

Anticipated Primary Completion Date :

Dec 15, 2022

Anticipated Study Completion Date :

Jul 3, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Sequence 1: Eptinezumab Then Placebo

Eptinezumab in the Placebo-controlled Period, followed by administration of placebo in the Active Treatment Period

Drug: Eptinezumab

Eptinezumab - concentrate for solution for infusion, intravenously

Drug: Placebo

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

Experimental: Sequence 2: Placebo Then Eptinezumab

Placebo in the Placebo-controlled Period, followed by administration of eptinezumab in the Active Treatment Period

Drug: Eptinezumab

Eptinezumab - concentrate for solution for infusion, intravenously

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Change From Baseline in Number of Weekly Attacks, Averaged Over Weeks 1-2 [Baseline, Weeks 1-2]

Secondary Outcome Measures

Percentage of Participants With ≥50% Reduction From Baseline in Number of Weekly Attacks [Weeks 1-2]
Change From Baseline in Weekly Number of Times an Abortive Therapy 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 Weekly Number of Days With Less Than 3 Attacks Per Day, Averaged Over Weeks 1-2 [Baseline, Weeks 1-2]
Time to Resolution of Cluster Headache Bout Within 4 Weeks After the First Investigational Medicinal Product (IMP) Infusion [From Baseline to Week 4]
Number of Attacks Starting Within 24 Hours of the Start of the First Infusion [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 to Week 1 in Number of Attacks [Baseline, Week 1]
Change From Baseline to Week 2 in Number of Attacks [Baseline, Week 2]
Percentage of Participants With ≥50% Reduction in Number of Attacks in Week 1 [Week 1]
Percentage of Participants With ≥30% Reduction in Number of Attacks in Week 1 [Week 1]
Percentage of Participants With ≥30% Reduction in Number of Weekly Attacks [Weeks 1-2]
Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of pain, Averaged Over Weeks 1-2 [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 [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 [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 [Baseline, Weeks 1-4]
Change From Baseline in Weekly Integrated Measure of Frequency and Intensity of Pain, Averaged Over Weeks 1-4 [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 [Baseline, Weeks 1, 2, 3, and 4]
Change From Baseline in Number of Attacks for Weeks 1, 2, 3, and 4 [Baseline, Weeks 1, 2, 3, and 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 [Baseline, Week 4]
General Health second version (WPAI:GH2.0) sub-scores (Absenteeism, Presenteeism, Work productivity loss, Activity impairment)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 a documented 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 ≤50 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	Mayo Clinic - Arizona	Phoenix	Arizona	United States	85054
3	Keck School of Medicine of the University of Southern California	Los Angeles	California	United States	90033
4	Clinical Research Institute	Los Angeles	California	United States	90048
5	Stanford Neurosciences Health Center	Palo Alto	California	United States	94304
6	Neurology Colorado - Denver Advanced Neurological Evaluation and Treatment Center	Denver	Colorado	United States	80218
7	Yale New Haven Hospital	New Haven	Connecticut	United States	06510-2483
8	New England Institute for Neurology and Headache	Stamford	Connecticut	United States	06905
9	Accel Research Sites - Tampa	Tampa	Florida	United States	33634
10	Diamond Headache Clinic	Chicago	Illinois	United States	60642
11	Michigan Headache and Neurological Institute	Ann Arbor	Michigan	United States	48104-5131
12	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
13	The Headache Center Mississippi	Ridgeland	Mississippi	United States	39157
14	Clinvest Research	Springfield	Missouri	United States	65810
15	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
16	Dent Neurologic Institute - Amherst	Amherst	New York	United States	14226
17	New York University School of Medicine	New York	New York	United States	10016
18	Headache Wellness Center	Greensboro	North Carolina	United States	27405
19	Cleveland Clinic - Neurological Institute	Cleveland	Ohio	United States	44195
20	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
21	Hightower Clinical	Oklahoma City	Oklahoma	United States	73134
22	Thomas Jefferson University Hospital - Center City Campus	Philadelphia	Pennsylvania	United States	19107
23	Mischer Neuroscience Institute	Houston	Texas	United States	77030
24	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
25	Universitair Ziekenhuis Brussel	Brussels	Bruxelles-Capitale	Belgium	1090
26	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge	West-Vlaanderen	Belgium	8000
27	Centre Hospitalier Chretien - Clinique MontLégia	Liège		Belgium	4000
28	Mestska Nemocnice Ostrava	Ostrava	Moravian-Silesian	Czechia	728 80
29	Neurologicka Ambulance - Forbeli	Praha 10	Prague	Czechia	160 00
30	Fakultní Thomayerova nemocnice	Praha 4	Prague	Czechia	140 59
31	Institut Neuropsychiatrické Péce	Praha 1	Praha	Czechia	110 00
32	Rigshospitalet Glostrup	Glostrup	Hovedstaden	Denmark	2600
33	Aarhus Universitetshospital	Aarhus N	Midtjylland	Denmark	8200
34	Hospitalsenhed Midt og Regionshospitalet Viborg	Viborg	Midtjylland	Denmark	8800
35	Sydvestjysk Sygehus - Esbjerg	Esbjerg		Denmark	6700
36	Confido Meditsiinikeskus	Tallinn	Harjumaa	Estonia	10138
37	Ida-Viru Keskhaigla	Kohtla-Järve	Ida-Virumaa	Estonia	31025
38	Tartu Ülikooli Kliinikum	Tartu	Tartumaa	Estonia	50406
39	Tampereen Yliopistollinen Sairaala	Tampere	Länsi-Suomen Lääni	Finland	33520
40	Terveystalo Ruoholahti	Helsinki	Southern Finland	Finland	00180
41	Terveystalo Turku Pulssi	Turku	Western Finland	Finland	20100
42	Terveystalo Tampere	Tampere		Finland	33100
43	Hôpital Cimiez	Nice Cedex 1	Côte-d'Or	France	91179 - 06003
44	Hôpital Roger Salengro	Lille	Nord	France	59037
45	Hôpital de la Timone	Marseille Cedex 5	Provence Alpes Cote d'Azur	France	13005
46	Hôpital Pierre Wertheimer	Bron	Rhone-Alps	France	69500
47	Centre Hospitalier Universitaire de Saint-Étienne	Saint-Priest-en-Jarez	Rhône	France	42055
48	Hôpital Lariboisière	Paris	ÃŽle-de-France	France	75010
49	Pineo Medical Ecosystem	Tbilisi		Georgia	0114
50	Archangel Saint Michael Multiprofile Clinical Hospital	Tbilisi		Georgia	0159
51	Aversi Clinic - Central Branch	Tbilisi		Georgia	0160
52	Simon Khechinashvili University Hospital	Tbilisi		Georgia	0179
53	Consilium Medulla Multiprofile Clinic	Tbilisi		Georgia	0186
54	Universität Heidelberg	Heidelberg	Baden-Württemberg	Germany	69120
55	LMU Klinikum - Campus Grosshadern	München	Bayern	Germany	D-81377
56	Kopfschmerzzentrum Frankfurt	Frankfurt/ Main	Hessen	Germany	65929
57	Universitätsmedizin Rostock	Rostock	Mecklenburg-Western-Pommerania	Germany	18147
58	Neurologische Praxis Dr. Stude	Bochum	Nordrhein-Westfalen	Germany	44787
59	Praxis für Neurologie, Psychosomatik, Nervenheilkunde, Psychotherapie und Spezielle Schmerztherapie	Essen	Nordrhein-Westfalen	Germany	45133
60	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45147
61	Universitatsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen	Germany	01307
62	Schmerzklinik Kiel	Kiel	Schleswig-Holstein	Germany	24149
63	Charité Campus Mitte	Berlin		Germany	10117
64	Eginition University - General Hospital of Athens	Athens	Attica	Greece	11528
65	401 General Military Hospital of Athens	Athina	Attica	Greece	115 25
66	Mediterraneo Hospital	Glyfada	Attica	Greece	16675
67	University General Hospital of Larissa	Larissa	Thessaly	Greece	41110
68	General Hospital of Patras Agios Andreas	Patra	Western Greece	Greece	263 32
69	Azienda Ospedaliero - Universitaria Careggi	Firenze	Florence	Italy	50134
70	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - San Raffaele Pisana	Rome	Roma	Italy	00163
71	Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari	Bari		Italy	70124
72	IRCCS Istituto Delle Scienze Neurologiche di Bologna	Bologna		Italy	40123
73	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Fondazione Istituto Neurologico Car...	Milano		Italy	20133
74	Azienda Ospedaliero - Universitaria di Modena	Modena		Italy	41124
75	Azienda Ospedaliera Universitaria - Universita degli Studi della Campania Luigi Vanvitelli	Napoli		Italy	280138
76	Fondazione Mondino - Istituto Neurologico Nazionale a Carattere Scientifico IRCCS	Pavia		Italy	27100
77	Universita Campus Bio-Medico di Roma	Rome		Italy	00128
78	Ospedale Molinette - Clinica Neurologica II - Centro Cefalee	Turin		Italy	10126
79	Sendai Headache And Neurology Clinic	Sendai-shi	Miyagi	Japan	982-0014
80	Saitama Neuropsychiatric Institute	Saitama-shi	Saitama	Japan	338-8577
81	Japanese Red Cross Shizuoka Hospital	Shizuoka-shi	Shizuoka	Japan	420-0853
82	Canisius-Wilhelmina Ziekenhuis	Nijmegen	Gelderland	Netherlands	6532 SZ
83	Brain Research Center - Amsterdam	Amsterdam	Noord-Holland	Netherlands	1081 GN
84	Oslo Hodepinesenter	Oslo		Norway	0275
85	Saint Olavs Hospital - Universitetssykehuset I Trondheim	Trondheim		Norway	7030
86	Hospital Prof. Doutor Fernando Fonseca	Amadora	Lisboa	Portugal	2720-276
87	Centro Hospitalar Universitario Lisboa Norte - Hospital De Santa Maria	Lisbon	Lisboa	Portugal	1649-035
88	Hospital Garcia de Orta	Almada		Portugal	2805-267
89	Hospital da Luz	Lisboa		Portugal	1500-650
90	City Hospital No. 33 of the Leninsky District of the city of Nizhny Novgorod	Nizhnij Novgorod	Nizhegorodskaya Oblast	Russian Federation	603076
91	Perm State Medical University named after E. A. Wagner of the Ministry of Healthcare of the Russi...	Perm	Permsky	Russian Federation	614990
92	Kazan State Medical University	Kazan	Tartarstan	Russian Federation	420012
93	First Moscow State Medical University named after I.M. Sechenov	Moscow		Russian Federation	119146
94	University Headache Clinic	Moscow		Russian Federation	121467
95	LLC Scientific and Practical Medical Center Innovation and Health	Novosibirsk		Russian Federation	630054
96	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
97	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid	Spain	28222
98	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
99	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
100	Hospital Universitari i Politècnic La Fe	Valencia		Spain	46026
101	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003
102	Hospital Clínico Universitario de Valencia	València		Spain	46010
103	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
104	Skåneuro Privatmottagning	Lund	Skåne Län	Sweden	222 22
105	Huddinge Hospital	Huddinge	Stockholms Län	Sweden	141 57
106	Danderyds Sjukhus	Stockholm	Stockholms Län	Sweden	182 88
107	Centralsjukhuset Karlstad	Karlstad	Värmlands Län	Sweden	651 85
108	Walton Centre NHS Foundation Trust	Liverpool	England	United Kingdom	L9 7LJ
109	King's College Hospital NHS Foundation Trust	London	England	United Kingdom	SE5 9PJ
110	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle-upon-Tyne	England	United Kingdom	NE7 7DN
111	Northern Care Alliance NHS Foundation Trust	Salford	England	United Kingdom	M6 8HD

Sponsors and Collaborators

H. Lundbeck A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

H. Lundbeck A/S

ClinicalTrials.gov Identifier:

NCT04688775

Other Study ID Numbers:

19386A

First Posted:

Dec 30, 2020

Last Update Posted:

Jul 14, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Cluster Headache

Headache

Study Results

No Results Posted as of Jul 14, 2022