A Study of Galcanezumab (LY2951742) in Adults With Treatment-Resistant Migraine

Migraine Clinical Trial

— CONQUER  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Adults With Treatment-Resistant Migraine - the CONQUER Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03559257
• Other study ID #: 16670
• Secondary ID: I5Q-MC-CGAW2018-
• Status: Completed
• Phase: Phase 3
• Start date: July 31, 2018
• Est. completion date: September 19, 2019

Study information

• Verified date: October 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and efficacy of galcanezumab in people with treatment-resistant episodic or chronic migraine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: September 19, 2019
• Est. primary completion date: June 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Have a diagnosis of migraine or chronic migraine.

• History of migraine headaches at least 1 year prior to screening, with onset prior to age 50.

• History of at least 4 migraine headache days and at, with at least 1 headache-free day per month on average within the past 3 months.

• Have documentation of 2 to 4 migraine preventive medication category failures due to inadequate efficacy or tolerability, in the past 10 years.

Exclusion Criteria:

• Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product.

• Current use or prior exposure to galcanezumab or another calcitonin gene-related peptide (CGRP) antibody.

• History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine).

• Pregnant or nursing.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Galcanezumab
Administered SC.
• Placebo
Administered SC.

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis St Jan Brugge	Brugge
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Aggarwal and Associates Ltd	Brampton	Ontario
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	DIEX Recherche Sherbrooke, Inc	Sherbrooke	Quebec
Czechia	Neurologicka ambulance, Neurologie Brno s.r.o.	Brno
Czechia	Brain-Soultherapy s.r.o	Kladno
Czechia	Clintrial, s.r.o.	Praha 10	Hl. M. Praha
Czechia	DADO MEDICAL, s.r.o.	Praha 2
Czechia	Neurologicka ordinace	Praha 6
Czechia	Institut Neuropsychiatricke Pece	Praha 8
France	CHRU de Lille- Hôpital Roger Salengro	Lille	Cedex
France	Hôpital de Cimiez	Nice
France	CHU St Etienne Hopital Nord	Saint Etienne Cedex 2
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Praxis Dr. Philipp Stude	Bochum	Nordrhein-Westfalen
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Jena	Jena	Thüringen
Germany	DRK-Kliniken Nordhessen	Kassel	Hessen
Hungary	Orszagos Idegtudomanyi Intezet	Budapest
Hungary	SE Neurologiai Klinika	Budapest
Hungary	Valeomed Kft.	Esztergom	Komarom-Esztergom
Japan	Doi Clinic Internal Medicine Neurology	Hiroshima
Japan	Tanaka neurosurgical clinic	Kagoshima
Japan	Medical corporation Shinmatsudakai Atago Hospital	Kochi-Shi	Kochi
Japan	Tatsuoka Neurology Clinic	Kyoto
Japan	Ooba Clinic for Neurosurgery & Headache	Oita
Japan	Tominaga Hospital	Osaka
Japan	Higashi Sapporo Neurology and Neurosurgery Clinic	Sapporo	Hokkaido
Japan	Sendai Headache and Neurology Clinic	Sendai	Miyagi
Japan	Dokkyo Medical University Hospital	Shimotsuga-Gun	Tochigi
Japan	Fukuuchi Pain Clinic	Shinjuku-ku	Tokyo
Japan	Shimoda Neurology Clinic	Tottori-shi	Tottori
Japan	Takase internal medicine clinic	Toyonaka-shi	Osaka
Korea, Republic of	Kangbuk Samsung Hosp	Seoul
Korea, Republic of	Nowon Eulji Medical Center, Eulji University	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen	Gelderland
Netherlands	Isala Klinieken	Zwolle
Puerto Rico	Instituto de Neurologia Dra. Ivonne Fraga	San Juan
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Marques De Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe de Valencia	Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
United Kingdom	Hull Royal Infirmary	Hull	East Yorkshire
United Kingdom	Kings College Hospital	London	Greater London
United Kingdom	St Thomas's Hospital	London
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Michigan Head, Pain and Neurological Institute	Ann Arbor	Michigan
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Boston Clinical Trials	Boston	Massachusetts
United States	PharmQuest	Greensboro	North Carolina
United States	Clinical Research Institute	Minneapolis	Minnesota
United States	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina
United States	Healthy Perspectives Innovative Mental Health Services, PL	Nashua	New Hampshire
United States	Health Research of Hampton Roads Inc	Newport News	Virginia
United States	Sensible Healthcare	Ocoee	Florida
United States	21st Century Neurology	Phoenix	Arizona
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Foothill Family Clinic	Salt Lake City	Utah
United States	Medical Center for Clinical Research	San Diego	California
United States	University of South Florida	Tampa	Florida
United States	Bio Behavioral Health	Toms River	New Jersey
United States	Renstar Medical Research	Wesley Chapel	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Japan,  Korea, Republic of,  Netherlands,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean is derived from the average of months 1 to 3 from mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 3
Secondary	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days in Participants With Episodic Migraine	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 3
Secondary	Percentage of Participants With =50% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Percentage of Participants With Episodic Migraine With =50% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with at least a 50% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1)	MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.	Baseline, Month 3
Secondary	Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) in Participants With Episodic Migraine	MSQ v2.1 is a health status instrument, with a 4-week recall period, developed to address physical and emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains:(1) Role Function-Restrictive (items 1-7);(2) Role Function- Preventive (items 8-11);&(3) Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6),& are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.	Baseline, Month 3
Secondary	Percentage of Participants With Episodic Migraine With =75% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Percentage of Participants With Episodic Migraine With 100% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Percentage of Participants With =75% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with at least a 75% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Percentage of Participants With 100% Reduction From Baseline in Monthly Migraine Headache Days	MHD: A calendar day on which a migraine headache or probable migraine headache occurred.; Overall mean percentage across months 1 through 3 of patients with 100% reduction in monthly MHDs from baseline using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly MHD.	Baseline, Month 1 through Month 3
Secondary	Overall Mean Change From Baseline in the Number of Monthly Days With Acute Headache Medication Use	Overall mean is derived from the average of months 1 to 3 from Mixed model repeated measures (MMRM) model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 3
Secondary	Overall Mean Change From Baseline in the Number of Monthly Headache Days	Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache).; Overall mean is derived from the average of months 1 to 3 from MMRM model. Least square (LS) Mean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 3
Secondary	Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total Score	The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missed or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LS mean was calculated using analysis of covariance (ANCOVA) with last observation carried forward (LOCF), with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the 4-item Migraine Interictal Burden Scale (MIBS-4)	MIBS-4 is a self-administered scale that measures the burden related to headache in the time between attacks. The instrument consists of 4 items that address disruption at work and school, diminished family and social life, difficulty planning, and emotional difficulty. The questionnaire specifically asks about the effect of the disease over the past 4 weeks on days without a headache attack. Response options include: don't know/not applicable (0), never (0), rarely (1), some of the time (2), much of the time (3), or most or all of the time (3). Each responses associated numerical score are summed across all 4 items resulting in a total score ranging from 0 to 12, and the level of interictal burden being categorized into the following: 0 for none, 1-2 mild, 3-4 moderate, and >5 severe. LS mean was calculated using MMRM model with fixed effects of treatment, pooled country, baseline migraine frequency category, month, treatment by month as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the Work Productivity and Activity Impairment Questionnaire (WPAI)	The WPAI Questionnaire is a patient-reported instrument developed to measure the impact on work productivity and regular activities attributable to a specific health problem (migraine). Recall period is the past 7 days. It contains 6 items that measure: 1) employment status, 2) hours missed from work due to the specific health problem, 3) hours missed from work for other reasons, 4) hours actually worked, 5) degree health affected productivity while working, and 6) degree health affected productivity in regular unpaid activities. Four scores are calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity loss, and activity impairment. Scores are calculated as impairment percentages (0-100%), with higher numbers indicating greater impairment and less productivity, i.e, worse outcomes. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S)	The PGI-S is a patient-rated instrument that measures illness severity. For this study, the patient was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" The PGI-S includes a range of possible responses, from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (US)	EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state. LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - Health State Index (UK)	EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the UK algorithm (-0.594 to 1). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3
Secondary	Mean Change From Baseline in the European Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) - VAS Score	EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. . The second part is assessed using a visual analog scale (VAS) on which the patient rates their perceived health state, ranging from 0 (the worst health you can imagine) to 100 (the best health you can imagine). LS mean was calculated using ANCOVA with LOCF with baseline, pooled country, baseline migraine frequency category, and treatment as fixed effects.	Baseline, Month 3

External Links

•   A Study of Galcanezumab (LY2951742) in Adults With Treatment-Resistant Migraine