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

Migraine Headache Clinical Trial

Official title:

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Patients With Episodic Migraine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02163993
• Other study ID #: 15414
• Secondary ID: I5Q-MC-CGAB
• Status: Completed
• Phase: Phase 2
• Start date: July 7, 2014
• Est. completion date: February 12, 2018

Study information

• Verified date: June 2017
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 414
• Est. completion date: February 12, 2018
• Est. primary completion date: August 19, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participants with a history of migraine of at least 1 year prior to enrollment.

• Migraine onset prior to age 50.

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 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.

Related Conditions & MeSH terms

• Headache
• Migraine Disorders
• Migraine Headache

Intervention

Drug:
• Galcanezumab
Administered SQ
• Placebo
Administered SQ

Locations

Country	Name	City	State
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Michigan Head, Pain and Neurological Institute	Ann Arbor	Michigan
United States	DermResearch	Austin	Texas
United States	FutureSearch Trials	Austin	Texas
United States	PharmaSite Research Inc	Baltimore	Maryland
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Boston Clinical Trials Inc	Boston	Massachusetts
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	Avail Clinical Research LLC	DeLand	Florida
United States	Otri-Med Corporation	Edgewood	Kentucky
United States	Pharmacology Research Institute, Long Beach	Encino	California
United States	Clinical Research Advantage	Gilbert	Arizona
United States	PharmQuest	Greensboro	North Carolina
United States	Westside Family Medical Center	Kalamazoo	Michigan
United States	Collaborative Neuroscience Network - CNS	Long Beach	California
United States	Pharmacology Research Institute, Long Beach	Los Alamitos	California
United States	Florida Clinical Research Center LLC	Maitland	Florida
United States	CNS Health Care	Memphis	Tennessee
United States	Dean Foundation for Health Research and Education	Middleton	Wisconsin
United States	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina
United States	Pharmacology Research Institute, Long Beach	Newport Beach	California
United States	Renstar Medical Research	Ocala	Florida
United States	Psychiatric Inst of Florida-Clinical Neuroscience Solutions	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	21st Century Neurology	Phoenix	Arizona
United States	Arizona Research Center	Phoenix	Arizona
United States	Island Neuro Associates,PC	Plainview	New York
United States	Summit Research Network Inc	Portland	Oregon
United States	Desert Valley Research	Rancho Mirage	California
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Mercy Health Research	Saint Louis	Missouri
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Medical Center for Clinical Research	San Diego	California
United States	San Francisco Clinical Research Center	San Francisco	California
United States	California Medical Clinic for Headache	Santa Monica	California
United States	North Seattle Womens Group	Seattle	Washington
United States	ClinVest	Springfield	Missouri
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Premiere Research Institute at Palm Beach Neurology	West Palm Beach	Florida
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Baseline, 12 Weeks
Secondary	Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Baseline, 12 Weeks
Secondary	Percentage of Participants With =50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Week 12
Secondary	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	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.	Baseline, 12 Weeks
Secondary	Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Baseline, 12 Weeks
Secondary	Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores	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.	Baseline, 12 Weeks
Secondary	Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores	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.	Baseline, 12 Weeks
Secondary	Serum Concentration of Galcanezumab	Blood serum concentrations of galcanezumab.	12 Weeks
Secondary	Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)	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).	12 Weeks
Secondary	Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab	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.	Baseline through 12 Weeks
Secondary	Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores	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.	Baseline through Week 12
Secondary	Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Baseline, 12 Weeks
Secondary	Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase	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.	Baseline, 12 Weeks