A Study of Galcanezumab in Participants With Chronic Cluster Headache

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with chronic cluster headache.

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of : Galcanezumab (LY2951742) With a Long-Term Open-Label Extension in Patients With Chronic Cluster Headache

Conditions
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Chronic Cluster Headache

Intervention / Treatment
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* Drug: Galcanezumab 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a history of chronic cluster headache occurring without a remission period, or with remissions lasting <1 month, for at least 1 year. Participants are able to distinguish cluster headache attacks from other headaches. 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 calcitonin-gene-related peptide (CGRP) antibody, any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF). Are taking indomethacin and/or are suspected of having another distinct trigeminal autonomic cephalalgia. A history of migraine variants that could implicate or could be confused with ischemia. Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins. A history or presence of other medical illness that indicates a medical problem that would preclude study participation. Evidence of significant active or unstable 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: Galcanezumab 300 mg<br>Double-Blind Treatment Phase: Participants received galcanezumab 300 mg once a month by subcutaneous (SC) injection for 3 months. Open-Label Treatment Phase: Participants received 300 mg galcanezumab by subcutaneous injections every 30 days, for up to a total of 12 administrations. | Drug: Galcanezumab 300 mg<br>* Administered SC<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo<br>Double-Blind Treatment Phase: Participants received placebo once a month by subcutaneous (SC) injection for 3 months. Open-Label Treatment Phase: Participants received 300 mg galcanezumab by subcutaneous injections every 30 days, for up to a total of 12 administrations. | Drug: Galcanezumab 300 mg<br>* Administered SC<br>* Other names: LY2951742;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 Weekly Cluster Headache Attack Frequency | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary, Baseline and 12 weeks of daily data during double-blind treatment phase will be converted into 14-calendar day intervals: the baseline 14-day interval, Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Next, the biweekly interval results were adjusted to 7-day (weekly) interval in order to report the outcome as weekly frequency. Overall mean change from baseline is derived from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, verapamil use, pooled investigative site, week, baseline, and treatment by week as fixed effects. | Baseline, Week 1 through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks | A 50% responder is any participant who has a ≥50% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval: Weeks 1/2, Weeks 3/4, Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects. | Baseline, Week 1 through Week 12 | 
| Percentage of Participants With a Sustained Response of 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks | Sustained Response is defined as a 50% or greater reduction in the weekly cluster attack frequency from baseline to Weeks 3/4 and maintained at Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Percentage of participants with a sustained response was analyzed using Koch's nonparametric randomization-based analysis of covariance method. This method adjusted for pooled investigative site by including it as a stratification variable. It also adjusted for sex, verapamil use and baseline value. | Baseline, Week 3 through Week 12 | 
| Percentage of Participants With a 30% Reduction in the Weekly Number of Cluster Headache Attacks | A 30% responder is any participant who has a ≥30% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval. Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects. . | Baseline, Week 1 through Week 12 | 
| Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects. | Week 4 | 
| Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects. | Week 8 | 
| Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects. | Week 12 | 
| Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 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 ideation: a yes answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. | Week 1 through Week 12 | 
| Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 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. | Week 1 through Week 12 | 
| Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab (LY2951742) | Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20. | Baseline, Week 1 through Week 12 | 
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Week 2 | 
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Week 4 | 
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Week 8 | 
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Week 12 |