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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine Headache
• Intervention / Treatment: Drug: Placebo; Drug: Galcanezumab

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Clinical Research Advantage
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85004
      • 21st Century Neurology
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute, Long Beach
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network - CNS
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute, Long Beach
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute, Long Beach
    • Rancho Mirage, California, United States, 92270
      • Desert Valley Research
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • San Diego, California, United States, 92013
      • Artemis Institute for Clinical Research
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center LLC
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32801
      • Psychiatric Inst of Florida-Clinical Neuroscience Solutions
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute at Palm Beach Neurology
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Otri-Med Corporation
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials Inc
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head, Pain and Neurological Institute
    • Kalamazoo, Michigan, United States, 49009
      • Westside Family Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
    • Springfield, Missouri, United States, 68507
      • Clinvest
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Plainview, New York, United States, 11803
      • Island Neuro Associates,PC
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network Inc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center, Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Health Care
  • Texas
    • Austin, Texas, United States, 78759
      • DermResearch
    • Austin, Texas, United States, 78731
      • FutureSearch Trials
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98105
      • North Seattle Womens Group
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation for Health Research and Education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5mg Galcanezumab; 5mg of galcanezumab given as subcutaneous (SQ) injections once every 28 days during a 12 week treatment period.	Drug: Galcanezumab; Administered SQ; Other Names: LY2951742
Experimental: 50mg Galcanezumab; 50mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period.	Drug: Galcanezumab; Administered SQ; Other Names: LY2951742
Experimental: 120mg Galcanezumab; 120mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period.	Drug: Galcanezumab; Administered SQ; Other Names: LY2951742
Experimental: 300mg Galcanezumab; 300mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period.	Drug: Galcanezumab; Administered SQ; Other Names: LY2951742
Placebo Comparator: Placebo; Placebo given as SQ injections once every 28 days during a 12 week treatment period.	Drug: Placebo; Administered SQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Serum Concentration of Galcanezumab	Blood serum concentrations of galcanezumab.	12 Weeks
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Stauffer VL, Turner I, Kemmer P, Kielbasa W, Day K, Port M, Quinlan T, Camporeale A. Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials. J Headache Pain. 2020 Jun 23;21(1):79. doi: 10.1186/s10194-020-01148-9.
• Bangs ME, Kudrow D, Wang S, Oakes TM, Terwindt GM, Magis D, Yunes-Medina L, Stauffer VL. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020 Jan 17;20(1):25. doi: 10.1186/s12883-020-1609-7. Erratum In: BMC Neurol. 2020 Mar 13;20(1):90.
• Kielbasa W, Quinlan T. Population Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, Following Subcutaneous Dosing to Healthy Individuals and Patients With Migraine. J Clin Pharmacol. 2020 Feb;60(2):229-239. doi: 10.1002/jcph.1511. Epub 2019 Sep 4.
• Skljarevski V, Oakes TM, Zhang Q, Ferguson MB, Martinez J, Camporeale A, Johnson KW, Shan Q, Carter J, Schacht A, Goadsby PJ, Dodick DW. Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):187-193. doi: 10.1001/jamaneurol.2017.3859. Erratum In: JAMA Neurol. 2018 Feb 1;75(2):260.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2014
• Primary Completion (Actual): August 19, 2015
• Study Completion (Actual): February 12, 2018

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 13, 2014
• First Posted (Estimate): June 16, 2014

Study Record Updates

• Last Update Posted (Actual): November 23, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache
• Other Study ID Numbers: 15414; I5Q-MC-CGAB (Other Identifier: Eli Lilly and Company)