A Study of Galcanezumab (LY2951742) in Participants With Migraine Headache
- Registration Number
- NCT02163993
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 414
- Participants with a history of migraine of at least 1 year prior to enrollment.
- Migraine onset prior to age 50.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo given as SQ injections once every 28 days during a 12 week treatment period. 5mg Galcanezumab Galcanezumab 5mg of galcanezumab given as subcutaneous (SQ) injections once every 28 days during a 12 week treatment period. 50mg Galcanezumab Galcanezumab 50mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. 120mg Galcanezumab Galcanezumab 120mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. 300mg Galcanezumab Galcanezumab 300mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Baseline, 12 Weeks 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores Baseline, 12 Weeks 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.
Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase Baseline, 12 Weeks 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.
Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Week 12 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.
Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase Baseline, 12 Weeks 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.
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) 12 Weeks 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).
Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab Baseline through 12 Weeks 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.
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 Baseline, 12 Weeks 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.
Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores Baseline, 12 Weeks 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.
Serum Concentration of Galcanezumab 12 Weeks Blood serum concentrations of galcanezumab.
Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores Baseline through Week 12 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.
Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Baseline, 12 Weeks 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.
Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Baseline, 12 Weeks 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.
Trial Locations
- Locations (38)
Clinical Research Advantage
🇺🇸Gilbert, Arizona, United States
PharmaSite Research Inc
🇺🇸Baltimore, Maryland, United States
Medical Center for Clinical Research
🇺🇸San Diego, California, United States
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
Pharmacology Research Institute, Long Beach
🇺🇸Newport Beach, California, United States
Artemis Institute for Clinical Research
🇺🇸San Diego, California, United States
Collaborative Neuroscience Network - CNS
🇺🇸Long Beach, California, United States
California Medical Clinic for Headache
🇺🇸Santa Monica, California, United States
Psychiatric Inst of Florida-Clinical Neuroscience Solutions
🇺🇸Orlando, Florida, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
Desert Valley Research
🇺🇸Rancho Mirage, California, United States
Premiere Research Institute at Palm Beach Neurology
🇺🇸West Palm Beach, Florida, United States
Westside Family Medical Center
🇺🇸Kalamazoo, Michigan, United States
Alpine Clinical Research Center
🇺🇸Boulder, Colorado, United States
Florida Clinical Research Center LLC
🇺🇸Maitland, Florida, United States
Otri-Med Corporation
🇺🇸Edgewood, Kentucky, United States
PharmQuest
🇺🇸Greensboro, North Carolina, United States
Albuquerque Clinical Trials
🇺🇸Albuquerque, New Mexico, United States
Island Neuro Associates,PC
🇺🇸Plainview, New York, United States
Avail Clinical Research LLC
🇺🇸DeLand, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Dean Foundation for Health Research and Education
🇺🇸Middleton, Wisconsin, United States
Rochester Clinical Research, Inc.
🇺🇸Rochester, New York, United States
FutureSearch Trials
🇺🇸Austin, Texas, United States
Northwest Clinical Research Center
🇺🇸Bellevue, Washington, United States
North Seattle Womens Group
🇺🇸Seattle, Washington, United States
Coastal Carolina Research Center, Inc.
🇺🇸Mount Pleasant, South Carolina, United States
Summit Research Network Inc
🇺🇸Portland, Oregon, United States
DermResearch
🇺🇸Austin, Texas, United States
Boston Clinical Trials Inc
🇺🇸Boston, Massachusetts, United States
Mercy Health Research
🇺🇸Saint Louis, Missouri, United States
ClinVest
🇺🇸Springfield, Missouri, United States
Michigan Head, Pain and Neurological Institute
🇺🇸Ann Arbor, Michigan, United States
New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
21st Century Neurology
🇺🇸Phoenix, Arizona, United States
Arizona Research Center
🇺🇸Phoenix, Arizona, United States
CNS Health Care
🇺🇸Memphis, Tennessee, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States