Clinical trial NCT02974153: Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine
Official title: A Parallel Group, Double-Blind, Randomized, Placebo Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of ALD403 Administered Intravenously in Patients With Chronic Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine Disorders
Lead sponsor: Alder Biopharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-28
Enrollment: 1121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the efficacy and safety of ALD403 in the prevention of migraine headache in chronic migraineurs.


Eligibility criteria: Inclusion Criteria:

* Males and females between 18 and 65 years of age, inclusive, who were diagnosed with migraines at ≤ 50 years of age, and have a history of chronic migraine for ≥ 12 months before screening.
* During the 28 day screening period, subjects must adequately complete the headache eDiary and must have headaches occurring on ≥ 15 to ≤ 26 days of which at least 8 must be migraine days.
* Headache eDiary was completed on at least 24 of the 28 days prior to randomization.

Exclusion Criteria:

* Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome).
* Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
* Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 4 months prior to screening and during the screening period.
* History or diagnosis of complicated migraine (ICHD-III beta version, 20134), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or sporadic and familial hemiplegic migraine.
* Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before screening.
* Previously dosed with ALD403 or any monoclonal antibody targeting the CGRP pathway.

Primary outcomes:
measure: Change From Baseline in Monthly Migraine Days
timeFrame: Week 1-12
Secondary outcomes:
measure: 75% Migraine Responder Rate
timeFrame: Week 1-12
measure: 75% Migraine Responder Rate - 4 Week
timeFrame: Week 1-4
measure: 50% Migraine Responder Rate
timeFrame: Week 1-12
measure: Percentage of Participants With a Migraine on the Day After Dosing
timeFrame: Day 1
measure: Change in Monthly Acute Medication Days
timeFrame: Week 1-12
measure: Change From Baseline of Headache Impact Test (HIT-6) Score
timeFrame: Baseline to Week 12
measure: Change in Migraine Prevalence From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: 75% Headache Responder Rate
timeFrame: Week 1-12
measure: 50% Headache Responder Rate
timeFrame: Week 1-12
measure: 100% Migraine Responder Rate
timeFrame: Week 1-12
measure: 100% Headache Responder Rate
timeFrame: Week 1-12
measure: Change From Baseline in Monthly Migraine Days (Weeks 13-24)
timeFrame: Week 13-24
measure: Change From Baseline in Monthly Headache Days (Weeks 1-12)
timeFrame: Week 1-12
measure: Time to First Migraine After Dosing
timeFrame: 32 weeks
measure: Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication
timeFrame: Week 1-12
measure: Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication
timeFrame: Week 1-12
measure: Percent Change in Frequency of Migraine Days - Week 1-12
timeFrame: Week 1-12
measure: Percent Change in Frequency of Headache Days - Week 1-12
timeFrame: Week 1-12
measure: Change From Baseline in Percentage of Severe Migraines
timeFrame: Week 1-12
measure: Change From Baseline in Percentage of Severe Headache
timeFrame: Week 1-12
measure: Change From Baseline in Monthly Migraine Hours, Weeks 1-12
timeFrame: Week 1-12
measure: Change From Baseline in Monthly Headache Hours, Weeks 1-12
timeFrame: Week 1-12
measure: Duration of Migraine-Free Intervals
timeFrame: 32 weeks
measure: Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
timeFrame: Baseline to Week 12
measure: Patient Global Impression of Change (PGIC) at Week 12
timeFrame: Week 12
measure: Health Related Quality of Life (EQ-5D-5L) at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Carlsbad
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facility: Research Site
state: California
city: Oceanside
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state: California
city: Orange
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state: California
city: Oxnard
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state: California
city: Palo Alto
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city: Redlands
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state: California
city: San Diego
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state: California
city: Santa Monica
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state: California
city: Torrance
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state: California
city: Colorado Springs
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state: Colorado
city: New London
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state: Connecticut
city: Jacksonville
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city: Miami
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city: Orlando
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city: Tampa
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city: West Palm Beach
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city: Winter Haven
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city: Atlanta
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state: Georgia
city: Atlanta
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state: Georgia
city: Decatur
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city: Champaign
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state: Illinois
city: Chicago
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city: Chicago
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state: Illinois
city: Anderson
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state: Indiana
city: Des Moines
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city: Overland Park
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state: Kansas
city: Prairie Village
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city: Waldorf
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state: Maryland
city: Boston
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state: Massachusetts
city: North Attleboro
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city: Watertown
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city: Dayton
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city: Smithfield
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city: Bellevue
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city: Brussels
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city: Liege
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city: Liège
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city: Choceň
country: Czechia
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city: Prague
country: Czechia
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city: Praha
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city: Glostrup
country: Denmark
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city: Viborg
country: Denmark
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city: Tbilisi
country: Georgia
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city: Tbilisi
country: Georgia
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country: Georgia
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city: Pavia
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city: Roma
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country: Russian Federation
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city: Kazan'
country: Russian Federation
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city: Krasnoyarsk
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city: Moscow
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl'
country: Russian Federation
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Dolný Kubín
country: Slovakia
facility: Research Site
city: Dubnica nad Vahom
country: Slovakia
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city: Krompachy
country: Slovakia
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city: Alicante
country: Spain
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city: Barcelona
country: Spain
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city: Guadalajara
country: Spain
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city: Lleida
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city: Madrid
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city: Madrid
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city: Madrid
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city: Madrid
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city: Navarrés
country: Spain
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city: Santander
country: Spain
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city: Sevilla
country: Spain
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city: Terrassa
country: Spain
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city: Valencia
country: Spain
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city: Valladolid
country: Spain
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city: Dnipropetrovs'k
country: Ukraine
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivs'k
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: L'viv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Inverness
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Stoke-on-Trent
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Pozo-Rosich P, Dodick DW, Ettrup A, Hirman J, Cady R. Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies. BMC Neurol. 2022 Oct 25;22(1):394. doi: 10.1186/s12883-022-02914-9.
citation: Cowan RP, Marmura MJ, Diener HC, Starling AJ, Schim J, Hirman J, Brevig T, Cady R. Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study. J Headache Pain. 2022 Sep 6;23(1):115. doi: 10.1186/s10194-022-01482-0.
citation: Apelian R, Boyle L, Hirman J, Asher D. Measuring dose-related efficacy of eptinezumab for migraine prevention: post hoc analysis of PROMISE-1 and PROMISE-2. J Headache Pain. 2022 Apr 18;23(1):48. doi: 10.1186/s10194-022-01418-8.
citation: McAllister P, Kudrow D, Cady R, Hirman J, Ettrup A. Reduction in migraine-associated burden after eptinezumab treatment in patients with chronic migraine. Cephalalgia. 2022 Sep;42(10):1005-1012. doi: 10.1177/03331024221089567. Epub 2022 Mar 25.
citation: Ashina M, McAllister P, Cady R, Hirman J, Ettrup A. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 Jul;42(8):696-704. doi: 10.1177/03331024221077646. Epub 2022 Mar 18.
citation: Buse DC, Winner PK, Charleston L 4th, Hirman J, Cady R, Brevig T. Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine. J Headache Pain. 2022 Feb 21;23(1):29. doi: 10.1186/s10194-022-01387-y.
citation: Martin V, Nagy AJ, Janelidze M, Giorgadze G, Hirman J, Cady R, Mehta L, Buse DC. Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2. Clin Ther. 2022 Mar;44(3):389-402. doi: 10.1016/j.clinthera.2022.01.006. Epub 2022 Feb 5.
citation: Lipton RB, Charleston L 4th, Tassorelli C, Brevig T, Hirman J, Cady R. Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a >/= 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials. J Headache Pain. 2022 Feb 7;23(1):23. doi: 10.1186/s10194-022-01386-z.
citation: Smith TR, Spierings ELH, Cady R, Hirman J, Ettrup A, Shen V. Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies. J Headache Pain. 2021 Nov 25;22(1):143. doi: 10.1186/s10194-021-01360-1.
citation: Smith TR, Spierings ELH, Cady R, Hirman J, Schaeffler B, Shen V, Sperling B, Brevig T, Josiassen MK, Brunner E, Honeywell L, Mehta L. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain. 2021 Mar 30;22(1):16. doi: 10.1186/s10194-021-01227-5.
citation: Silberstein S, Diamond M, Hindiyeh NA, Biondi DM, Cady R, Hirman J, Allan B, Pederson S, Schaeffler B, Smith J. Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study. J Headache Pain. 2020 Oct 6;21(1):120. doi: 10.1186/s10194-020-01186-3.
citation: Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, Allan B, Cady R. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020 Mar 31;94(13):e1365-e1377. doi: 10.1212/WNL.0000000000009169. Epub 2020 Mar 24.