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

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

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

Conditions
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Migraine

Intervention / Treatment
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* Drug: Galcanezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galcanezumab<br>Galcanezumab administered subcutaneously (SC). | Drug: Galcanezumab<br>* Administered SC.<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo<br>Placebo administered SC. | Drug: Placebo<br>* Administered SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prevention, prophylaxis, headache, treatment-resistant, treatment resistant