A Study of LY2951742 in Participants With Migraine

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Migraine

To assess the efficacy and safety of LY2951742 in the prevention of migraine headache in migraineurs with or without aura during 3 months of treatment.

Study Overview

• Status: Completed
• Conditions: Migraine Headache
• Intervention / Treatment: Drug: Placebo; Drug: LY2951742

Detailed Description

The study is comprised of 4 trial periods:

1. Screening and washout (5-45 days)
2. Baseline for assessment of the type, frequency, and severity of headaches (28-38 days)
3. Treatment (12 weeks)
4. Follow-up (12 weeks)

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Neurological Physicians of Arizona / Clinical Research Advantage
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Foundation for Medical Education and Research - Mayo Clinic
  • California
    • Encino, California, United States, 91316
      • PRI Encino
    • Huntington Beach, California, United States, 92647
      • Allergy and Asthma Specialists Medical Group
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network Inc.
    • Los Alamitos, California, United States, 90720
      • PRI Los Alamitos
    • Newport Beach, California, United States, 92660
      • PRI Newport Beach
    • San Diego, California, United States, 92108
      • Medical Center for Clinical Research
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
    • San Francisco, California, United States, 94115
      • University of California, San Francisco (UCSF) Medical Center - Headache Center
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache Inc
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research - Denver
  • Florida
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center LLC
    • Melbourne, Florida, United States, 32935
      • Accelovance, Inc
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Pembroke Pines, Florida, United States, 33026
      • Broward Research Group
    • Sunrise, Florida, United States, 33351
      • Neurology Clinical Research Inc
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research
  • Michigan
    • Kalamazoo, Michigan, United States, 49009
      • Westside Family Medical Center, Pc
  • Missouri
    • Chesterfield, Missouri, United States, 63141
      • Ryan Headache Center, St. John's Mercy Medical Group
    • Springfield, Missouri, United States, 65807
      • Clinvest, A Division of Banyan Group, Inc.
  • Nebraska
    • Fremont, Nebraska, United States, 68025
      • Prarie Fields Medicine/Clinical Research Advantage
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Clinical Research Advantage
    • Henderson, Nevada, United States, 89014
      • James Meli DO Ltd (Clinical Research Advantage)
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • COR Clinical Research, LLC
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research of Bristol
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch
    • Nashville, Tennessee, United States, 37203
      • Nashville Neuroscience Group
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology and Sleep Lab
    • Austin, Texas, United States, 78759
      • Neurology Studies of Austin, A Division of DermResearch Inc.
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network (CTN Texas)
  • Virginia
    • McLean, Virginia, United States, 22102
      • Neurology & Headache Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a history of migraine as defined by the International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004) of at least 1 year prior to enrollment, migraine onset prior to age 50, and a moderate frequency of migraine headaches
• Women of child-bearing potential (not surgically sterile or at least 1 year post-menopause) must test negative for pregnancy at the time of screening based on a serum pregnancy test and must agree to use a reliable method of birth control during the study and for 3 months following completion of participation in the study
• Have clinical laboratory test results within normal reference ranges or, if outside the normal range, judged not clinically significant by the Investigator
• Must not be on any migraine prevention therapy, including botulinum toxin (Botox)
• Agree not to post any personal medical data related to the study or information related to the study on any website or social media site (for example, Facebook, Twitter, et cetera) until the trial has completed

Exclusion Criteria:

• Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device, or concurrent enrollment in any other type of medical research judged not to be scientifically or medically compatible with this study
• Previous completion or withdrawal from this study or any other study investigating LY2951742 or other therapeutic antibodies that target calcitonin gene-related peptide (CGRP)
• History of chronic migraine or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine
• History of headache (for example, cluster headache or Medication Overuse Headache [MOH]) other than migraine or tension type headache as defined by IHS ICHD-II within 12 months prior to randomization
• Evidence of significant active psychiatric disease including, but not limited to, manic depressive illness, schizophrenia, generalized anxiety disorder, obsessive compulsive disorder, personality disorders, or other serious mood, anxiety, depression, or substance use disorders
• Have a history or presence of any other medical illness that in the judgment of the Investigator, indicates a medical problem that would preclude study participation
• Women who are pregnant or nursing
• Confirmed corrected QT (QTc) interval >470 milliseconds (msec) for women and >450 for men
• Excessive alcohol, opiate, or barbiturate use; history of drug abuse or dependence
• In the opinion of the Investigator, have no other issues that would interfere with compliance with the study requirements and completion of evaluations required for this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2951742; LY2951742: 150 milligrams (mg), subcutaneous (SC) injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period.	Drug: LY2951742
Placebo Comparator: Placebo; Placebo: 0.9% Sodium Chloride, Untied States Pharmacopoeia (USP), subcutaneous (SC) injection on Day 1 and then once every other week for a total of 6 doses during the 12-week Treatment Period.	Drug: Placebo

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 II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). 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-II 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 square (LS) means were calculated using mixed model repeated measures (MMRM) with baseline value, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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-II guidelines 1.1 and 1.2 (Cephalgia 2004). Definition of MH was headache with or without aura, of ≥30 min duration, and with both ("A" and "B") required features from IHS ICHD-II 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 baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.	Baseline, 12 weeks
Mean Change From Baseline in the 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 for a migraine headache was adapted from the standard IHS ICHD-II guidelines 1.1 and 1.2 (Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both ("A" and "B") required features from the IHS ICHD-II 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. LS means were calculated using MMRM with baseline value, gender, treatment, month, and treatment-by-month interaction as fixed effects and participant as random effect.	Baseline, 12 weeks
Percentage of Responders	Percentage of participants with greater than 50% reduction in the number of migraine headache days in a 28-day period. The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders II guidelines 1.1 and 1.2 (ICHD-II, Cephalgia 2004). The definition of a migraine headache was a headache with or without aura, of ≥30 minutes duration, and with both ("A" and "B") required features from the IHS ICHD-II 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, 4, 8, and 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.
• Goadsby PJ, Dodick DW, Martinez JM, Ferguson MB, Oakes TM, Zhang Q, Skljarevski V, Aurora SK. Onset of efficacy and duration of response of galcanezumab for the prevention of episodic migraine: a post-hoc analysis. J Neurol Neurosurg Psychiatry. 2019 Aug;90(8):939-944. doi: 10.1136/jnnp-2018-320242. Epub 2019 Apr 19.
• Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014 Sep;13(9):885-92. doi: 10.1016/S1474-4422(14)70128-0. Epub 2014 Aug 10.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): September 18, 2013

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: June 21, 2012
• First Posted (Estimate): June 22, 2012

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: April 1, 2014

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: ART-01 (Other Identifier: Eli Lilly and Company)