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

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as Galcanezumab in Japanese participants with migraine.

Official Title
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A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 (Galcanezumab) in Japanese 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: For Episodic Migraine participants: Participants who completed the treatment period of Galcanezumab study CGAN. Have a diagnosis of chronic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (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. Exclusion Criteria: For Chronic Migraine participants: 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 other antibodies of calcitonin gene-related peptide (CGRP) or its receptor. Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to Galcanezumab and the excipients in the investigational product. 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. Failure to respond to 3 or more adequately dosed migraine preventive treatments from different classes (that is, maximum tolerated dose for at least 2 months).

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: 120mg/120mg Galcanezumab - Episodic Migraine (EM)<br>240 milligram (loading dose) of Galcanezumab at first dosing visit followed by 120 milligram (mg) once a month for a year by subcutaneous (SC) injection. EM participants (pts) rolled over from CGAN (NCT02959177) 120 mg Galcanezumab. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: 240mg/240mg Galcanezumab - EM<br>240 mg Galcanezumab given SC once a month for a year. EM participants rolled over from CGAN (NCT02959177) 240 mg Galcanezumab. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: Placebo/ 120mg Galcanezumab - EM<br>240 mg (loading dose) of Galcanezumab at first dosing visit followed by 120 mg once a month for a year by SC injection. EM participants rolled over from CGAN (NCT02959177) placebo. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: Placebo/ 240mg Galcanezumab - EM<br>240 mg Galcanezumab given SC once a month for a year. EM participants rolled over from CGAN (NCT02959177) Placebo. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: 120mg Galcanezumab - CM<br>240 mg (loading dose) of Galcanezumab at first dosing visit followed by 120 mg once a month for a year by SC injection. Participants with CM were enrolled. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: 240mg Galcanezumab - CM<br>240 mg Galcanezumab given SC once a month for a year. Participants with CM were enrolled. | 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 |
| --- | --- | --- |
| Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | A TEAE started on or after the date and time of the first dose of study drug administered in this study, or started prior to the study drug administration but worsened after the study drug started. Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events module. | Up To 16 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Serum Concentration of Galcanezumab at month 12 is reported. | Month 12: Predose | 
| Pharmacodynamics (PD): Plasma Concentration of Total Calcitonin Gene-Related Peptide (CGRP) | Plasma Concentration of total CGRP at month 12 is reported. | Month 12: Predose | 
| Percentage of Participants Developing Anti-Drug Antibodies (ADA) | Treatment emergent ADA will be defined as any of the following: A negative baseline result and a positive post-baseline ADA result with a titer ≥20. This is also called treatment-induced ADA. A positive baseline result and a positive post-baseline ADA result with a ≥4-fold increase in titers (for example, baseline titer of 10 increasing to ≥40 post-baseline). This is called treatment-boosted ADA. | Month 0, 1, 2, 3, 6, 9, 12 and 16: Predose; Month 0 and 14 days Postdose | 
| Mean Change From Baseline in the Number of Migraine Headache Days (MHDs) | Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache (EM Participants): A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia. Migraine Headache (CM Participants) : A headache, with or without aura, of greater than or equal to (≥30) minutes duration which meets criteria A and B or meets criterion C: A and B criteria as described above and criteria C) The headache is believed by the participant to be migraine at onset and is relieved by a triptan or ergot derivative. | Baseline, Month 12 | 
| Mean Change From Baseline in the Number of Headache Days (HDs) | A headache day is calendar day on which any type of headache occurs,(including migraine headache, probable migraine headache, and non-migraine headache). | Baseline, Month 12 | 
| Percentage of Participants With Meeting Criteria for Reductions From Baseline Greater Than or Equal to (≥) 50% in Number of Migraine Headache Days | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 50% responder in a particular month is any participant who has a ≥50% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. | Month 12 | 
| Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine Headache | Migraine Headache Day (MHD) with Acute Medication Use: Calendar days on which migraine or probable migraine occurs, requiring acute medication. | Baseline, Month 12 | 
| Mean Change From Baseline in the Number of Monthly Migraine Headache Days or Headache Days Requiring Medication for the Acute Treatment of Migraine Headache or Headache | Monthly Migraine Headache Days or Headache Days Requiring Medication for the Acute Treatment of Migraine Headache or Headache: Calendar days on which headache, migraine or probable migraine occurs, requiring acute medication. | Baseline, Month 12 | 
| Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score | The PGI-S scale is a patient-rated instrument that measures patients own global impression of their illness severity. The patient was instructed as follows: Considering migraine as a chronic condition, how would you rate your level of illness? Response options were from 1 (normal, not at all ill) to 7 (extremely ill). | Baseline, Month 12 | 
| 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. | Baseline, Month 12 | 
| Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 | MSQ version 2.1 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 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 (5 categories). Preference compared 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 (5 categories). The side effects responses range from significantly less side effects to significantly more side effects (5 categories). Positive responses for each item were defined as follows: Satisfaction: Very Satisfied or Somewhat Satisfied; Preference: Much Prefer Study Medication or Prefer Study Medication; Side Effects: Much-Less Side Effects or Less Side Effects. | Month 12 | 

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