A Safety Study of Galcanezumab in Participants With Migraine, With or Without Aura

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the longer term safety of the study drug known as galcanezumab in participants with episodic or chronic migraine.

Official Title
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A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 in Patients With Migraine

Conditions
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Migraine

Intervention / Treatment
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* Drug: Galcanezumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of episodic or chronic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1, 1.2 or 1.3) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, and migraine onset prior to age 50. Prior to baseline, a history of 4 or more migraine headache days per month on average for the past 3 months. 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 CGRP antibody. Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to galcanezumab. 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) defined by IHS ICHD-3 beta.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galcanezumab 120 mg<br>Galcanezumab 240mg given as loading dose at first dosing visit followed by 120 mg given by subcutaneous (SC) injection once a month for up to 11 months by auto injector or pre-filled syringe. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: Galcanezumab 240 mg<br>Galcanezumab 240 mg given by SC injection once a month for up to 12 months by auto injector or pre-filled syringe. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Discontinued Due to Adverse Event | Adverse Event: Any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A summary of other non-serious AEs, and all SAE's, regardless of causality, is reported in the Adverse Events section. | Baseline through Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab | Baseline through Month 12 | 
| Serum Concentrations of Galcanezumab | Serum Concentrations of Galcanezumab. | Month 12 | 
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Month 12 | 
| Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab | A Treatment Emergent Anti-drug Antibody (TE ADA) evaluable participant is considered to be TE ADA+ if the participant 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 (treatment-induced). There were 6 participants in the 120 mg arm who discontinued after receiving loading dose of 240mg, these participants were moved to 240mg arm for safety analysis. | Month 1 through Month 12 | 
| Overall Mean Change From Baseline in the Number of Migraine Headache Days (MHD) | 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 12 from MMRM model. Least squares mean (LSMean) was calculated using mixed model repeated measures (MMRM) model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. | Baseline, Month 1 through Month 12 | 
| Overall Mean Change From Baseline in the Number of 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 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. | Baseline, Month 1 through Month 12 | 
| Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days | Migraine Headache Day: A calendar day on which a migraine headache or probable migraine headache occurred. Overall percentage of participants with a given response rate were estimated from the generalized linear mixed models (GLIMMIX) model. | Baseline, Month 1 through Month 12 | 
| Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches | Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects. | Baseline, Month 1 through Month 12 | 
| Overall Mean Patient Global Impression-Improvement (PGI-I) Score | The Patient Global Impression of Improvement (PGI -I) scale is a participant-rated instrument that measures the participants own global impression of their symptom improvement. The participant was instructed as follows: Mark the box that best describes your migraine headache condition since you started taking this medicine. Response options were on a 7-point scale in which a score of 1 indicates that the participant's condition is very much better, a score of 4 indicates that the participant has experienced no change, and a score of 7 indicates that the participant is very much worse. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline PGI-S, and baseline PGI-S by month as fixed effects. | Month 1 through Month 12 | 
| Overall Mean Change From Baseline on 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 missing 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. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month. | Baseline, Month 1 through Month 12 | 
| Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | MSQv2.1 is a health status instrument,with a 4-week recall period, developed to address physical & 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 addressing 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 total raw score is computed for each domain & total score, 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 1 through Month 12 | 
| Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) | The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from very unsatisfied to very satisfied with the current treatment. Preference compares the current study medication to previous medications, with responses from much rather prefer my previous medication to much rather prefer the medication administered to me during the study. | Baseline through Month 12 | 
| Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12 | The SQAAQ is a self-administered questionnaire that provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of study drug. Participants will respond to questionnaire items using a 7-point Likert scale (from Strongly Disagree to Strongly Agree) shortly after the injection. If a caregiver administers the injection, the participants should be prepared to provide the caregiver's ratings of the questions.strongly agree & agree are considered as positive responses. | Baseline through Month 12 | 

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