A Study of Galcanezumab (LY2951742) in Participants With Migraine Headache

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate whether the study drug known as galcanezumab is safe and effective in the prevention of migraine headaches.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Patients With Episodic Migraine

Conditions
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Migraine Headache

Intervention / Treatment
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* Drug: Galcanezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a history of migraine of at least 1 year prior to enrollment. Migraine onset prior to age 50. Exclusion Criteria: Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device. Current use or any prior exposure to any CGRP antibody, any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF). History of migraine subtypes including hemiplegic migraine, ophthalmoplegic migraine, and basilar-type migraine. Have a history or presence of other medical illness that indicates a medical problem that would preclude study participation. Failure to respond to more than two adequately dosed effective migraine prevention treatments. Evidence of significant active psychiatric disease, in the opinion of the investigator. Women who are pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: 5mg Galcanezumab<br>5mg of galcanezumab given as subcutaneous (SQ) injections once every 28 days during a 12 week treatment period. | Drug: Galcanezumab<br>* Administered SQ<br>* Other names: LY2951742;|
| Experimental: 50mg Galcanezumab<br>50mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | Drug: Galcanezumab<br>* Administered SQ<br>* Other names: LY2951742;|
| Experimental: 120mg Galcanezumab<br>120mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | Drug: Galcanezumab<br>* Administered SQ<br>* Other names: LY2951742;|
| Experimental: 300mg Galcanezumab<br>300mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | Drug: Galcanezumab<br>* Administered SQ<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo<br>Placebo given as SQ injections once every 28 days during a 12 week treatment period. | Drug: Placebo<br>* Administered SQ<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) mean was calculated using mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. | Baseline, 12 Weeks | 
| Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. | Week 12 | 
| Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. | Baseline, 12 Weeks | 
| Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | Number of headache hours calculated as the total number of headache hours in a 28-day period on which a headache occurred. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | MSQL consists of 14 questions across 3 dimensions (role function-restrictive, role function-preventive, and emotional function). All question values range from 1 to 6. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recorded before item scores were calculated. Then, dimension scores were calculated as the sum of the recorded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive function = [(dimension score-7)*100]/35, for the preventive function = [(dimension score-4)*100]/20, and for the emotional function = [(dimension score-3)*100]/15. A lower score indicated a poorer quality of life associated with that domain. LS means was determined by Analysis of covariance (ANCOVA) with treatment, pooled investigative site and baseline. | Baseline, 12 Weeks | 
| Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | The HIT-6 consists of 6 questions to measure the impact of headaches on the participants ability to function on the job, at school, at home and in social situations. A score to each question will be assigned as follows: never - 6, rarely - 8, sometimes - 10, very often - 11, and always - 13. The composite score is calculated as the sum of the scores for all 6 questions, the total score ranges between 36 and 78 with higher total scores reflecting more severe impact of headaches. LS means was determined by ANCOVA with treatment, pooled investigative site and baseline. | Baseline, 12 Weeks | 
| Serum Concentration of Galcanezumab | Blood serum concentrations of galcanezumab. | 12 Weeks | 
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | CGRP has been shown to be involved in the pathophysiology of migraine through dilation of cerebral and dural blood vessels, release of inflammatory mediators, and transmission of nociceptive (pain) information from intracranial blood vessels to the nervous system (Villalón and Olesen 2009). In migraineurs, serum concentrations of CGRP are significantly elevated during migraine attacks (Goadsby et al. 1990; Goadsby and Edvinsson 1993). | 12 Weeks | 
| Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | The percent of participants with treatment emergent Anti-drug Antibodies (ADA) were assessed at week 1 to 12. A participant was considered to have treatment-emergent Galcanezumab ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as any of the following: A negative baseline ADA result and a subsequent positive post-baseline ADA result with a titer >=20; or a positive ADA results and a subsequent positive post-baseline ADA results with a 4-fold or greater increase in titer from the baseline measurement. | Baseline through 12 Weeks | 
| Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. | Baseline through Week 12 | 
| Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-3 beta definition. It is defined as headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. | Baseline, 12 Weeks | 
| Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Number of calendar days on which headache lasts ≥4 hrs it includes migraines, PM & non-migraines. MH is headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea &/or vomiting, or photophobia & phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. Severity was measured via interactive voice response system questionnaire What was the worst headache pain? For mild press 1. For moderate 2. For severe press 3. LSmean was calculated using MMRM with treatment, pooled investigative site, period, treatment-by-period interaction, baseline and baseline-by-period interaction. | Baseline, 12 Weeks |