Evaluation of Efficay & Safety of Galcanezumab in the Prevention of Episodic Migraine- the EVOLVE-2 Study

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

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Episodic Migraine - the EVOLVE-2 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 as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta version (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, migraine onset prior to age 50 and MONTHLY frequency of 4-14 MHD. 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. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galcanezumab 120mg<br>Galcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: Galcanezumab 240mg<br>Galcanezumab 240mg given by SC injection once a month for 6 months. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo<br>Placebo given by SC injection once a month for 6 months. | Drug: Placebo<br>* Administered SC<br>|
| Experimental: Galcanezumab 120mg Maximum Extended Enrollment Cohort<br>Galcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Experimental: Galcanezumab 240mg Maximum Extended Enrollment Cohort<br>Galcanezumab 240mg given by SC injection once a month for 6 months. | Drug: Galcanezumab<br>* Administered SC<br>* Other names: LY2951742;|
| Placebo Comparator: Placebo Maximum Extended Enrollment Cohort<br>Placebo given by SC injection once a month for 6 months. | 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. Migraine Headache : 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; Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects. | Baseline, Month 1 through Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache Days | Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline. | Baseline, Month 1 through Month 6 | 
| Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive Domain | MSQ v2.1 was developed to address physical & emotional limitations of specific concern to individuals with migraine. 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. Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month & baseline MHD category as fixed factors. | Baseline, Month 4 through Month 6 | 
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache | 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 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects. | Baseline, Month 1 through Month 6 | 
| Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) Rating | The PGI-S scale is a participant-rated instrument that measures patients own global impression of their illness severity. The participant 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). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors. | Baseline, Month 4 through Month 6 | 
| Overall Mean Change From Baseline in Headache Hours | Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category. | Baseline, Month 1 through Month 6 | 
| 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 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. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors. | Baseline, Month 6 | 
| Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab | 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. | Month 1 through Month 6 | 
| Pharmacokinetics (PK): Serum Concentrations of Galcanezumab | Pharmacokinetics (PK): Serum Concentrations of Galcanezumab. | Month 6 | 
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP). | Month 6 | 

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